TW200932732A

TW200932732A - 5-O-substituted 3-N-phenyl-1,3,4-oxadiazolones for medical use

Info

Publication number: TW200932732A
Application number: TW097150238A
Authority: TW
Inventors: David Alexander Learmonth; Laszlo Erno Kiss; Alexander Beliaev; Humberto Dos Santos Ferreira; Silva Patrcio Manuel Vieira Araujo Soares Da
Original assignee: Bial Portela & Companhia S A
Priority date: 2007-12-27
Filing date: 2008-12-23
Publication date: 2009-08-01
Also published as: CN101959881A; AU2008344032A1; ZA201005306B; MX2010006995A; AR069970A1; CA2710743A1; KR20100111691A; JP2011507952A; CL2008003895A1; AU2008344032A8; EP2238131A1; WO2009084970A1; IL206419A0; BRPI0821482A2

Abstract

The present invention relates to compounds having a 5-O-substituted 3-N-phenyl-l, 3, 4-oxadiazolone structural unit which have unexpectedly high level of inhibition of FAAH (fatty acid amide hydrolase).

Description

200932732 六、發明說明：【發明所屬之技術領域】本發明係有關於具有一個5-0-取代3-N-苯基-1,3,4-咬一唑酮結構單元之化合物’其具有意外高的FAAH(脂肪酸 5 醯胺水解酶)抑制作用水平。【先前技術j FAAH是一種水解生物活性醯胺諸如内生性類***素極樂醯胺(anandamide)之整合膜蛋白（IMP)，其係游離脂肪酸與乙醇胺之類***素受體與TRPV1類香草素受體之同效 10 劑’如見McKinney Μ· K.、Cravatt B. F.於期刊“Λη”. 执Wiem.”第74期第411頁（2005年）乙文。鑑於其調控極樂醢胺(anandamide)水平之能力，FAAH 是目前受到矚目的一種藥物標的。FAAH抑制劑的實例包括 PMSF(苯基甲基磺醯氟）、MAFP(甲氧基花生四烯基氟膦酸 15 酯）及ATMK(花生四烯醢基三氟甲基酮），而URB597 ([3-(3- 胺基甲醯基苯基)苯基]N-環己基胺基甲酸酯）廣泛地被認為是目前的“黃金本位制”FAAH抑制劑。在臨床前的實驗室試驗發現’ URB597增加内生性類***素之製造，而產生可測得的抗憂鬱與止痛效應，如見RussoR.等人於期刊‘V 20 P/iannaco/ 77ier.” 第 322(1)期第 236-42(2007年）乙文。 FA A Η抑制作用被認為在廣泛種類的醫學病況中扮演一重要角色，如見Pacher等人於期刊第58 期第389-462頁（2006年）乙文，其在此完整地併入本案以為參考資料。 3 200932732 FAAH抑制作詩及下列病況： ⑴疼痛，_是急諸如偏與神經病變疼痛（例如糖尿病性神經病變疼痛、范療後神經痛、三叉神經痛）；與炎性疾病諸如關節炎、類風濕性關節炎、骨關 5節炎、脊椎炎、痛風、血管炎、克隆氏(Cr〇hn)病及激躁性腸症候群相§請之急性或慢轉痛；急性或慢，關邊疼痛； ⑼暈眩"區吐及叙、，特別是因化療而起的； (ill)飲食失調病症’特暇厭食症與不同性質的惡病質； (IV)神經與精神病變，諸如震顫、運轉礙、肌張力障 10礙痙攣’強迫妄想行為、妥瑞(Tourette)症候群、所有形式的憂鬱症及任-性質與起源的焦慮症、情緒症及精神病； (v) 急性與慢性神經退化性疾病，諸如巴金森氏 (Parkinson)症、阿兹海默氏(Alzheimer)症老年癡呆症、杭丁頓氏（Huntington)舞蹈症與大腦局部缺血及與顱部與骨 15 髓外傷相關之病灶； (vi) 癲癇症； (vii) 睡眠障礙，包括睡眠窒息症； (V111)心血管疾病’諸如心臟衰竭、高血壓、心律不整、動脈硬化、心臟病發作、心臟局部缺血及腎臟局部缺血； 20 (1X)癌症’例如良性皮膚腫瘤、腦腫瘤與乳突瘤、前列腺腫瘤及大腦腫瘤（神經膠質母細胞瘤、髓上皮瘤、髓質母細胞瘤、神經母細胞瘤、胚源性腫瘤、星狀細胞瘤、上皮性腫瘤、室官膜瘤、募樹突神經膠質瘤、叢腫瘤、神經上皮瘤、松果體腫瘤、室管膜母細胞瘤、惡性腦膜瘤、肉瘤 200932732 病、惡性黑色素瘤及神經鞘瘤）； 5 10 15 e 20 00免疫系統失調，特別是自體免疫疾病諸如牛皮癬、紅斑性狼瘡、結締組織的疾病或膠原疾病、修格蘭氏 (Sj0gren)症候群、僵直性脊椎炎、未分化型脊椎炎、貝西氏(Behcet)病 '自體免疫型溶血性貧血、多發性硬化症、肌萎縮性脊髓側索硬化症、澱粉樣病變、移植體排斥作用、影響漿細胞株之疾病、過敏性疾病；速發型或遲發型過敏反應、過敏性鼻炎或結膜炎、接觸性皮膚炎； (XI) 寄生蟲、病毒或細菌性傳染病諸如Aros與腦膜炎； (XII) 炎性疾病，特別是關節疾病諸如關節炎、類風濕性關節炎、骨關節炎、脊椎炎、痛風、血管炎'克隆氏(crohn) 病、激躁性腸症候群； (xiii) 骨質疏鬆症； (xiv) 眼部病況，諸如高眼壓與青光眼； (xv) 肺部病況，包括呼吸道疾病、支氣管痙孿、咳嗷、氣喘、慢性支氣管炎' 慢性呼吸道阻塞及肺氣腫； (XVI)胃腸疾病，諸如激躁性腸症候群、發炎性腸病症、潰瘍、腹瀉、尿失禁及膀胱發炎。 t ^^明内穷】發現具有—個5-0-取代3-N-苯基-1，3,4-吱二唑酮結構單元之化合物，其具有意外高的FAAH抑制作用水平，使得 4等化合物成為用於治療或預防FAAH相關醫學病況之具潛力的候選藥物。而，亦已在於活體内試驗中證實該活性之存在。 5 200932732 另外在該等活體内試驗中，意外地發現具有一個5_〇_ 取代3-N-苯基-l，3,4-呋二唑酮結構單元之化合物顯示一種 FAAH抑制性活性，該活性對於週圍神經之選擇性優於對於中枢神經系統的活性。因而預期該等化合物的投藥作用， 5 將降低對於中樞神經的副作用，該副作用係在對於週圍神經並無選擇性的FAAH抑制劑之情況下所見。因此，本發明的化合物可用於治療上所提及的病況，以及用於製備治療該等病況之藥物。本發明亦包括治療該等疾病之方法，其包括對於需要的一病患投予本發明的一 10化合物，以及含有本發明的一或多種化合物之藥學組成物。本發明的化合物所預期之最佳用途，係用於治療疼痛，特別是： -治療急性或慢性神經痛，例如偏顧與神經病變疼痛包括糖尿病性神經病變疼痛、疱疹後神經痛、三叉神 15 經痛； — 人…相關聯之急性或慢性疼痛，諸如關節炎、類風濕性關節炎、骨關銘* 月關卽炎、脊椎炎、痛風、血吉病 '激躁性腸症候群；及 -急性或慢性周邊疼痛。 20 如用於此之‘治療作用，，一詞及其變體療的”，係指可嘉東化療或冶 ^ 人類或非人類動物之任一太土吃、Α 療作用可針對一現在& 方法。該治見存的病況，或可為預防性(預治療作料包括力心哨防性治療）。 α癒性、減緩性或預防性作用。、、Λ 止或延緩疾病或病況之L μ 下用/台療可阻炳况之發病’阻滯其進程或改善其徵狀。 200932732 5-0-取代3-N-苯基-1，3,4-呋二唑酮係述於數個公開案中，諸如第5,093,343號美國專利、第5,236,939號美國專利、第4,〇76,824號美國專利、第WO 03/043997 A1號專利、第EP 1263745 B1 專利、第 w〇 03/072098 A1 專利、第 WO 01/ H9S1 A1 專利、第 WO 03/〇72555 A1 專利及第 JP-A4858140 專利。然而’該等公開案中並無一者係有關於FAAH抑制作用，或關於FAAH相關醫學病況之治療。 C實施方式3 ❹ 10 Ο 15 在一實施例中，本發明係有關於具化學式⑴的一化合物：200932732 VI. Description of the invention: [Technical field to which the invention pertains] The present invention relates to a compound having a 5-0-substituted 3-N-phenyl-1,3,4-bitazolone structural unit which has an accident High FAAH (fatty acid 5 guanamine hydrolase) inhibitory levels. [Prior Art j FAAH is an integrated membrane protein (IMP) that hydrolyzes bioactive guanamine such as endogenous cannabinoid anandamide, which is a cannabinoid receptor such as free fatty acid and ethanolamine and a class of vanillin of TRPV1. The same effect of 10 doses, see McKinney Μ K., Cravatt BF in the journal "Λη". Obtain Wiem." 74th, 411 (2005). In view of its regulation of anandamide levels FAAH is currently the subject of a drug that is attracting attention. Examples of FAAH inhibitors include PMSF (phenylmethylsulfonium fluoride), MAFP (methoxy-pentyltetradecylfluorophosphonate 15 ester), and ATMK (Peanut IV). Iridyl trifluoromethyl ketone), while URB597 ([3-(3-aminomethylmercaptophenyl)phenyl] N-cyclohexyl carbazate) is widely considered to be the current "gold standard" "FAAH inhibitors." Preclinical laboratory tests have found that URB597 increases the production of endogenous cannabinoids, producing measurable antidepressant and analgesic effects, as seen in Russo R. et al. in the journal 'V 20 P/ Iannaco/ 77ier.” No. 322(1) No. 236-42 (2007). FA A Η inhibition is thought to play an important role in a wide variety of medical conditions, as seen in Pacher et al., Journal No. 58, pp. 389-462 (2006), which is hereby incorporated in its entirety. Reference materials. 3 200932732 FAAH inhibits poetry and the following conditions: (1) pain, _ is acute such as partial and neuropathic pain (such as diabetic neuropathic pain, post-therapy neuralgia, trigeminal neuralgia); and inflammatory diseases such as arthritis, rheumatoid Sexual arthritis, bone inflammation, spondylitis, gout, vasculitis, Crohn's disease and stimulating bowel syndrome, please call acute or slow pain; acute or slow, pain at the edge; (9) dizziness " vomiting and narration, especially due to chemotherapy; (ill) eating disorders 'special anorexia and different nature of cachexia; (IV) neurological and psychiatric disorders, such as tremors, disturbances, Muscle tone disorder 10 obstructs 'forced delusional behavior, Tourette syndrome, all forms of depression and any-attraction and origin of anxiety, mood and psychosis; (v) acute and chronic neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, Alzheimer's disease, Huntington's chorea and cerebral ischemia, and lesions associated with cranial and bone 15 pith trauma; (vi Epilepsy (vii) Sleep disorders, including sleep apnoea; (V111) Cardiovascular diseases such as heart failure, hypertension, arrhythmia, arteriosclerosis, heart attack, cardiac ischemia and renal ischemia; 20 (1X) cancer 'For example, benign skin tumors, brain tumors and mastoid tumors, prostate tumors and brain tumors (glioblastoma, myeloma, medulloblastoma, neuroblastoma, embryogenic tumor, astrocytoma, Epithelial tumors, ventricular stromal tumors, dendritic gliomas, plexus tumors, neuroepithelial neoplasia, pineal tumors, ependymioblastoma, malignant meningioma, sarcoma 200932732 disease, malignant melanoma and schwannomas 5 10 15 e 20 00 Immune system disorders, especially autoimmune diseases such as psoriasis, lupus erythematosus, connective tissue disease or collagen disease, Sjögren syndrome, ankylosing spondylitis, undifferentiated Spondylitis, Behcet's autoimmune hemolytic anemia, multiple sclerosis, amyotrophic lateral sclerosis, amyloidosis, graft rejection Effects, diseases affecting plasma cell lines, allergic diseases; immediate or delayed allergic reactions, allergic rhinitis or conjunctivitis, contact dermatitis; (XI) parasitic, viral or bacterial infectious diseases such as Aros and meningitis; (XII) inflammatory diseases, especially joint diseases such as arthritis, rheumatoid arthritis, osteoarthritis, spondylitis, gout, vasculitis 'crohn' disease, stimulating bowel syndrome; (xiii) bone (xiv) ocular conditions, such as high intraocular pressure and glaucoma; (xv) pulmonary conditions, including respiratory diseases, bronchospasm, cough, asthma, chronic bronchitis' chronic airway obstruction and emphysema; XVI) Gastrointestinal diseases such as irritable bowel syndrome, inflammatory bowel disease, ulcers, diarrhea, urinary incontinence and bladder inflammation. t ^^明内穷] Found a compound having a 5-0-substituted 3-N-phenyl-1,3,4-oxadiazolone structural unit with an unexpectedly high level of FAAH inhibition, such that 4 Compounds have potential drug candidates for the treatment or prevention of FAAH-related medical conditions. However, the existence of this activity has also been confirmed in an in vivo test. 5 200932732 In addition, in such in vivo experiments, it was unexpectedly found that a compound having a 5_〇_ substituted 3-N-phenyl-1,3,4-furadiazolone structural unit exhibits a FAAH inhibitory activity, The activity is more selective for peripheral nerves than for the central nervous system. It is therefore expected that the administration of these compounds, 5 will reduce the side effects on the central nervous system, which are seen in the case of FAAH inhibitors which are not selective for peripheral nerves. Thus, the compounds of the invention are useful in the treatment of the conditions mentioned, as well as in the preparation of a medicament for the treatment of such conditions. The invention also includes a method of treating such diseases comprising administering a compound of the invention to a patient in need thereof, and a pharmaceutical composition comprising one or more compounds of the invention. The preferred use of the compounds of the present invention is for the treatment of pain, in particular: - treatment of acute or chronic neuralgia, such as palpation and neuropathic pain including diabetic neuropathic pain, post-herpetic neuralgia, trigeminal 15 Menstrual pain; - humans associated with acute or chronic pain, such as arthritis, rheumatoid arthritis, bone Guanming * Yue Guan Yan, spondylitis, gout, bloody disease 'irritating bowel syndrome; and - acute or chronic Pain around. 20 As used in this 'therapeutic effect, the term and its variants,' refers to any of the human or non-human animals that can be used for chemotherapy or smelting. Method: The condition of the treatment, or may be prophylactic (pre-treatment treatment includes force-whistle prevention treatment). α, palliative or prophylactic effect, , or delay or delay the disease or condition μ under the use of / Taiwan treatment can prevent the onset of the disease's block its progress or improve its symptoms. 200932732 5-0-substituted 3-N-phenyl-1,3,4-furadiazolone is described in the number In the case of the disclosure, such as U.S. Patent No. 5,093,343, U.S. Patent No. 5,236,939, U.S. Patent No. 4, U.S. Patent No. 4,766,824, U.S. Patent Application Serial No. WO 03/043,997, filed No. , WO 01/H9S1 A1 patent, WO 03/〇72555 A1 patent and JP-A 4858140 patent. However, none of the publications relates to FAAH inhibition or treatment of FAAH-related medical conditions. C. Embodiment 3 ❹ 10 Ο 15 In one embodiment, the present invention relates to a chemical formula (1) a compound:

R4 R5R4 R5

—(C=X)n—(CH2)m—Y (I) 其中 R至R5係彼此獨立地代表：氣；—(C=X)n—(CH2)m—Y (I) wherein R to R5 are independently of each other: gas;

Cl_CV院基、C3'c8-環燒基、C6-C10-芳基、c6-c10-芳基Cl-C8_烧基、CrCV烧氧基、C6-C1Q-芳氧基、c6-c10-芳基c, C8-烧氧丨、Ci_c6燒氧基幾基、芳氧基獄基、C6-Cl(r方基-Cl'C8·、虎氧基縣、crc6-烷基羰基、 C6 C!。-方基·縣、C6_Ci。芳基烧基幾基、Ci_c6烧基叛基、C6_C1G·芳基通基、Ci_c6烧基氫硫基、c6_c⑺芳基氫硫基、C^CV；^基㈣n 環烧基魏基幾基c6-c10-方基疏基羰基、烧基魏基缓基、 7 20 200932732 芳基巯基羧基、C1-C6-烧基磺醯基、c6-c1(r芳基磺醢基、 Cj-CV烷基氧硫基、CVQo-芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次：Cl_CV, C3'c8-cycloalkyl, C6-C10-aryl, c6-c10-aryl Cl-C8_alkyl, CrCV alkoxy, C6-C1Q-aryloxy, c6-c10-aryl Base c, C8-oxygen oxime, Ci_c6 alkoxy group, aryloxy phenyl group, C6-Cl (r-aryl-Cl'C8·, oxime county, crc6-alkylcarbonyl, C6 C!. - 方基·县, C6_Ci. arylalkyl group, Ci_c6 alkyl group, C6_C1G. aryl group, Ci_c6 alkylthio group, c6_c(7) aryl thio group, C^CV; ^ group (tetra) n ring Pyridyl-Wiki-based c6-c10-aryl-based carbonyl, alkyl-based thiol, 7 20 200932732 aryl fluorenylcarboxy, C1-C6-alkylsulfonyl, c6-c1 (rarylsulfonyl) a group, a Cj-CV alkyl oxythio group, a CVQo-aryl oxythio group, each of which is optionally substituted one or more times by:

CrC6-烷基；CrQ-烷氧基；c6-C10-芳氧基； 5 co2h ; so3h ; conh2 ; so2nh2 ; CONH2 或 SO2NH2 ’CrC6-alkyl; CrQ-alkoxy; c6-C10-aryloxy; 5 co2h; so3h; conh2; so2nh2; CONH2 or SO2NH2 ’

其中該胺基官能度被選自CrC6-烷基、C6-Cht芳基或 C6-C10-芳基-CrC4-烷基的殘基取代一次或多次’及其中在一種經二-CrCV烷基取代的胺基官能度之情況下’該烷基殘基可結合而形成5或6員環；胺基；經選自下列群 1〇中的殘基取代一或多次之胺基：CrC6-烷基、G-Cm芳基、C6-C1()-芳基-CrC4-烷基、CVCV烷基羰基、c6-ci〇_ 芳基羰基、Q-CV烷基磺醯基及C6-C1()-芳基磺醯基；琉氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基；械代基；cf3或ocf3 ; 15 co2h ; so3H;Wherein the amine functionality is substituted one or more times by a residue selected from the group consisting of CrC6-alkyl, C6-Cht aryl or C6-C10-aryl-CrC4-alkyl' and in a di-CrCV alkyl group In the case of a substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of: CrC6- Alkyl, G-Cm aryl, C6-C1()-aryl-CrC4-alkyl, CVCV alkylcarbonyl, c6-ci〇_arylcarbonyl, Q-CV alkylsulfonyl and C6-C1 ( --arylsulfonyl; anthracenyl; hydroxy; nitro; cyano; fluoro; carbyl; bromo; mechanical substituent; cf3 or ocf3; 15 co2h;

胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6_ 淀基、C6-C10-芳基、C6-C1。-芳基-Ci-C6_烧基、C1-C6-烧基 20 羰基、c6-c1(r芳基羰基、Crc6-烷基磺醯基及Q-Cur芳基磺醯基；具下列化學式（II)之一種經二取代的胺基；Amine; one or more amine groups substituted with a residue selected from the group consisting of CrC6_ decyl, C6-C10-aryl, C6-C1. -aryl-Ci-C6-alkyl, C1-C6-alkyl 20 carbonyl, c6-c1 (rarylcarbonyl, Crc6-alkylsulfonyl and Q-Cur arylsulfonyl; having the following chemical formula ( a disubstituted amino group of II);

—N—N

〇 (II) 8 200932732 其中〇代表0或1，而w代表氧、CH2或NR6，R6係選自氫與CVC6-烷基，及其中化學式(11)中的亞甲基可選擇性地被CrCV烷基、氟代基或氣代基取代一或二次； conh2 ； 5 ❹ 10 15 ❹ 20 so2NH2; CONH2或S02NH2，其中該胺基官能度被選自q-Q-烧基、C6_Ci〇-方基或C6-Ci〇-方基-C]-C6-烧基的殘基取代·—或二次’及其中在一種經二-Cl_C6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；硫氫基；羥基；硝基；氰基；氣確酿基；選自氟代基、氯代基、溴代基或蛾代基之函素； cf3 ; OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次： CVQ-烧基；CrC6-烧氧基；c〇〇H ; S〇3jj . CONH2，SO2NH2，CONH2 或 SO2NH2，其中該胺基官 < 度被選自CrC6-烧基、C6-C1(r芳基或C6-C10-芳基烧基的殘基取代一次或多次，及其中在一種經二_ c 、’ 一烧基取代的胺基官能度之情況下，該燒基殘基可結人 9 200932732 形成5或6員環；職；闕自下解巾的殘基取代一或多次之胺基：Cl_c6_烧基、C6_Ci。芳基、。芳基 -CrQ-烧基、Cl-C6_院基幾基、C6_Ci◦芳基縣、Ci C6_ 烧基項醯基及C6-C10-芳基續醯基；硫氫基；經基；硝 5 基，氰基，氟代基；氯代基：漠代基；埃代基；CF3或 OCF3 ; 及其中R1至R5中之任二或多者，可結合而形成祠合的飽和、不飽和或芳族同環或雜環系統；〇(II) 8 200932732 wherein 〇 represents 0 or 1, and w represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and CVC 6-alkyl, and the methylene group in the formula (11) is optionally CrCV Alkyl, fluoro or ke group substituted one or two times; conh2; 5 ❹ 10 15 ❹ 20 so2NH2; CONH2 or S02NH2, wherein the amine functionality is selected from qQ-alkyl, C6_Ci〇-square or C6-Ci〇-square-C]-C6-alkyl residue substitution-- or secondary ' and its alkyl residue in the case of a di-Cl_C6-alkyl substituted amine functionality The group may be combined to form a 5- or 6-membered ring; a sulfhydryl group; a hydroxyl group; a nitro group; a cyano group; a gas-based base; a fluoro group, a chloro group, a bromo group or a mothyl group; cf3 OCF3; or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, which is optionally substituted one or more times by: CVQ-alkyl; CrC6-alkoxy; C〇〇H ; S〇3jj . CONH2, SO2NH2, CONH2 or SO2NH2, wherein the amine group is selected from the group consisting of CrC6-alkyl, C6-C1 (r-aryl or C6-C10-arylalkyl) Replacing residues one or more times And in the case of an amine functional group substituted by a bis-c, 'monoalkyl group, the alkyl residue can form a 9 or 32 member ring; 2009; Substituting one or more amine groups: Cl_c6_alkyl, C6_Ci. aryl, aryl-CrQ-alkyl, Cl-C6_inhoally, C6_Ci◦aryl, Ci C6_ alkyl And C6-C10-aryl sulfhydryl; sulfhydryl; transbasic; nitrate 5, cyano, fluoro; chloro: molybdenum; edetyl; CF3 or OCF3; and R1 to R5 thereof Any two or more of them may be combined to form a coupled saturated, unsaturated or aromatic homocyclic or heterocyclic ring system;

η代表0或 1 ; m代表〇、1、2、3、4、5或6 ; Q 10 X代表氧或硫； Y代表： > a)氫； ioCkCw烧基、單元不飽和或多元不飽和C2_Ci8亞烧基、C3-C8-環烧基、C6-C10-芳基、C6-C10-芳基烧 15 基、Ci-C6-院氧基、C6-C1(r芳氧基、C6-Cl(r芳基·Ci_c8_烷氧基、CrCV烷氧基羰基、C6-C1()-芳氧基羰基、c6_Cl〇_芳基-CrCV烧氧基艘基、CrC6-：^基幾基、C6-C1()-芳基幾 Ο 基、CVCio-芳基-Ci-Cg-烧基叛基、Ci-C6-烧基叛基、 C6-C1()-芳基叛基、Ci_C6_烧基氫硫基、C6-C1()-芳基氫硫 20 基、Q-CV烷基巯基羰基、c3-c8-環烷基鲸基羰基、 c6-c1(r芳基巯基羰基、CVCV烷基酼基羧基、c6-c10-芳基疏基幾·基、Ci_C6_炫*基績酿基、C6-C]。-芳基績酿基、 C〗-C6-烧基氧硫基、C6-Ci〇-方基氧硫基或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其中各者 10 200932732 選擇性地被下列各者取代一次或多次： • bUQ-CV 烷基、C3-C8-環烷基、C6-C1()-芳基、 • C6-C〗。-芳基-CVC8-烷基、CVCV烷氧基、c6-c1(r芳氧基、C6-C1()-芳基-CrCV烷氧基、CkCV烷氧基羰基、 5 c6-c1()-芳氧基羰基、C6-C1(r芳基-CVC8-烷氧基羰基、 crc6-烷基羰基、c6-c1(r芳基羰基、c6-c1(r芳基-crc8-烷基羰基、CrCV烷基羧基、C6-C1()-芳基羧基、Q-C6-烷基氮硫基、C6-Ci〇-芳基氯硫基、Ci_C6-烧基威基裁基、 ® C3-C8-環烷基巯基羰基、C6-C1()-芳基Μ基羰基、CrC6-烷 10 基酼基羧基、C6-C1(r芳基Μ基羧基、CrC6-烷基磺醯 ' 基、c6-c1(r芳基磺醯基、crc6-烷基氧硫基、c6-c10-芳 • 基氧硫基；其中各者選擇性地被下列各者取代一次或多次：Q-CV烷基；CVC6-烷氧基；conh2、so2nh2 ;其中該胺基官能度被CVC6-烷基取代一次或二次之conh2 15 或so2nh2 ; so3h ; C02H ;胺基；經選自下列群中的殘基取代一或多次之胺基：CrC^-烷基、c6-c10-芳基、 ❹ C6_Ci〇-芳基-Ci_C6_烧基、Ci-C6-烧基幾基、C6-Ci〇-芳基羰基、crc6-烷基磺醯基及C6-C1Q-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基；碘 20 代基；CF3 ;或OCF3 ; 其中bl)中的數個取代基可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統；或被： b2)羥基；硫氫基；硝基；氰基；氟代基；氣代基； 11 200932732 溴代基·’破代基；CF3 ; C〇2H ; s〇3H ; OCF3 ; CONH2 ; SO2·2 ; C0NH2 或 S〇2Nh2，其中該胺基官能 . 度被選自（VQ-烷基、C6-C10-芳基或C6_Ci〇_芳基_Ci_C6_ . 烷基的殘基取代一或二次，及其中在一種經二^ (^-烷 5 基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烧基、c6-c1()-芳基、C6_Ci『芳基_Ci_C8_ 烷基、crC6-烷基羰基、C6-c1()-芳基羰基、Ci_C6_烷基磺酿基及CVCw芳基確醯基；或具下列化學式（I〗)之一種 ❹ 10 經二取代的胺基：η represents 0 or 1; m represents 〇, 1, 2, 3, 4, 5 or 6; Q 10 X represents oxygen or sulfur; Y represents: > a) hydrogen; ioCkCw alkyl, unit unsaturated or polyunsaturated C2_Ci8 alkylene group, C3-C8-cycloalkyl group, C6-C10-aryl group, C6-C10-aryl group 15 base, Ci-C6-homoyloxy group, C6-C1 (r aryloxy group, C6-Cl (raryl·Ci_c8_alkoxy, CrCV alkoxycarbonyl, C6-C1()-aryloxycarbonyl, c6_Cl〇_aryl-CrCV alkoxy group, CrC6-:yl group, C6 -C1()-aryl benzyl, CVCio-aryl-Ci-Cg-alkyl group, Ci-C6-alkyl group, C6-C1()-aryl group, Ci_C6_alkyl group Thio group, C6-C1()-arylhydrosulfuryl 20 group, Q-CV alkylmercaptocarbonyl group, c3-c8-cycloalkyl whale carbonyl group, c6-c1 (r aryl fluorenylcarbonyl group, CVCV alkyl fluorenyl group Carboxyl, c6-c10-arylsulfanyl, Ci_C6_Hyun* base, C6-C]-aryl base, C--C6-alkyloxythio, C6-Ci〇 a aryloxythio group or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, each of which 10 200932732 is optionally substituted one or more times by: • bUQ-CV Alkyl, C3 -C8-cycloalkyl, C6-C1()-aryl, • C6-C. -Aryl-CVC8-alkyl, CVCV alkoxy, c6-c1 (r aryloxy, C6-C1() -aryl-CrCV alkoxy, CkCV alkoxycarbonyl, 5 c6-c1()-aryloxycarbonyl, C6-C1 (raryl-CVC8-alkoxycarbonyl, crc6-alkylcarbonyl, c6- C1(r arylcarbonyl, c6-c1 (raryl-crc8-alkylcarbonyl, CrCV alkylcarboxy, C6-C1()-arylcarboxy, Q-C6-alkylthio group, C6-Ci〇 -Aryl chlorothio, Ci_C6-alkylcarbyl, ® C3-C8-cycloalkylcarbonylcarbonyl, C6-C1()-aryldecylcarbonyl, CrC6-alkanylmethylcarbonyl, C6- C1 (raryldecylcarboxyl, CrC6-alkylsulfonyl), c6-c1 (rarylsulfonyl, crc6-alkyloxythio, c6-c10-aryloxythio; each of which Optionally substituted by one or more of the following: Q-CV alkyl; CVC6-alkoxy; conh2, so2nh2; wherein the amine functionality is replaced by CVC6-alkyl once or twice conh2 15 or So2h ; C02H ; amine group; amine group substituted one or more times by a residue selected from the group consisting of: CrC^-alkyl, c6-c10-aryl, ❹C6_Ci〇-aryl-Ci_C6_ Base, Ci-C6-alkyl a benzyl, a C6-Ci 〇-arylcarbonyl group, a crc6-alkylsulfonyl group, and a C6-C1Q-arylsulfonyl group; a sulfhydryl group; a hydroxyl group; a nitro group; a cyano group; a fluoro group; a bromo group; an iodine 20 alkyl group; CF3; or OCF3; wherein several substituents in bl) may combine to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; or by: b2) hydroxyl group Sulfhydryl; nitro; cyano; fluoro; gas; 11, 200932, 32, bromo, 'deactivated; CF3; C〇2H; s〇3H; OCF3; CONH2; SO2·2; C0NH2 or S〇2Nh2, wherein the degree of the amine functionality is one or two times selected from the group consisting of (VQ-alkyl, C6-C10-aryl or C6_Ci〇_aryl-Ci_C6_. alkyl residue, and one of them The alkyl residue may be bonded to form a 5 or 6 membered ring; the amine group; one or more substituted with a residue selected from the group consisting of the following groups; Amino group: crc6-alkyl, c6-c1()-aryl, C6_Ci "aryl-Ci_C8_ alkyl, crC6-alkylcarbonyl, C6-c1()-arylcarbonyl, Ci_C6_alkyl sulphur And a CVCw aryl group; or one of the following chemical formulas (I) Disubstituted amine 10:

(Π) 其中〇代表0或1 ’而W代表氧、ch2或NR6，而R6係選自氫與Ci-C6·烧基，及其中化學式(η)中的亞甲基可選 15 擇性地被心-(：6-烷基、氟代基或氣代基取代一或二次；或被：(Π) where 〇 represents 0 or 1 ' and W represents oxygen, ch2 or NR6, and R6 is selected from hydrogen and Ci-C6·alkyl, and the methylene in the chemical formula (η) is optionally selected 15 Substituted one or two times by a heart-(:6-alkyl, fluoro or a gas group; or by:

b3)—種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統’其選擇性地被(^-(：6-烷基取代一或多次；Ci-C6-烧氧基；COOH ; so3h ; conh2 ; so2nh2 ; C0NH2或SC^NH2，其中該胺基官能度被選自C「C6_烧 20 基、C6_Cl(r芳基或C6_Ci〇-芳基-Ci-C4-烷基的殘基取代一次或多次，及其中在一種經二-CVC6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基： 12 200932732B3) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms' selectively substituted by (^-(6-alkyl substituted one or more times; Ci-C6-burning oxygen) COOH; so3h; conh2; so2nh2; C0NH2 or SC^NH2, wherein the amine functionality is selected from C"C6_烧20 base, C6_Cl(r aryl or C6_Ci〇-aryl-Ci-C4-alkane) Substituting a residue one or more times, and wherein in the case of a di-CVC6-alkyl substituted amine functionality, the alkyl residue can be combined to form a 5 or 6 membered ring; an amine group; Substituents selected from the following groups are substituted for one or more amine groups: 12 200932732

CrC6-烧基、C6-C10-芳基、C6_C10-芳基-C1-C4-烧基、Ci-C6_ 烷基羰基、C6-C1()-芳基羰基、Ci-Ce-烷基磺醯基及C6-C10-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；CF3或OCF3 ; 5 ❹ 10 15 20 c)S03H ;胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6-烧基、C6-C1()-芳基、C6-C1()-芳基-CrC8-烧基、Q-C6-烷基羰基' c6-c1()-芳基羰基、CVC6-烷基磺醯基及 c6- c10-芳基績醯基；conh2 ; so2nh2 ; CONH2 或 S〇2NH2 ’其中該胺基官能度被選自Q-CV烧基、c6-c10-芳基或Ce-CiQ-方基-Ci-C6-烧基的殘基取代一或二次，及其中在一種經二-CrC6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；硫氫基；羥基；硝基；氰基，氟續醯基；選自氟代基、氯代基、溴代基或破代基之鹵素；CF3 ;或〇CF3 ; 或其-種立體麟物、藥學上可接受的雜錢或前驅藥物。另一實施例係有關於上述化合物在抑制脂肪酸醯胺水解酶(FAAH)之用途，及在治療因FAAH抑制作用而受到正面影響的醫學病況之用途。尤其在Pacher等人於期刊，，尸Wm⑽Ζ.^ν·“第58期第389_462頁（2_年）乙文中，特別指出上述化合物在治療所提及的疾病與醫學病況之用途。本發明亦有關於-種藥學組成物，其包括具上述化學式(I)之-化合物或其-對映異構物、藥學上可接受的鹽類或-前驅藥物’以及有關於藉由投予—藥學活性量之:上述化學式⑴的-化合物、其—對映異構物、藥學上可接受 13 200932732 的鹽類或一前驅藥物，而用於治療上所提及的疾病與醫學病況之一種方法。在本申請案之的内涵中，“crc4-烷基”一詞較佳代表曱基、乙基、正-丙基、異丙基、正-丁基、仲-丁基及特-丁基。 5 在本申請案之的内涵中，“CrC6-烷基”一詞較佳代表曱基、乙基、正-丙基、異丙基、正-丁基、仲-丁基、特-丁基、戊基或己基。在本申請案之的内涵中，“crc18-烷基”一詞較佳代表甲基、乙基、正-丙基、異丙基、正-丁基、仲-丁基、特-丁 10 基、戊基、己基、辛基、癸基、十二烧基、十四烧基及十八烧基。在本申請案之的内涵中，“單元不飽和或多元不飽和的 c2-c18-亞烷基”一詞較佳代表乙烯基、正-丙烯基、異丙烯基、正-丁烯基、仲-丁烯基、特-丁烯基、戊烯基、己烯基、 15 辛烯基、癸烯基、十二碳稀基、十四碳稀基、十八碳稀基、十二碳二烯基、十四碳二烯基及十八碳二烯基在本申請案之的内涵中，“c3-c8-環烷基” 一詞較佳代表環丙基、環丁基、環戊基或環己基。在本申請案之的内涵中，c6-c10-芳基一詞較佳代表苯 20 基、並環戊二烯基、茚基、茚滿基、異吲哚滿基、色原烷基、萘基、芴基、蒽基、菲基或芘基。在本申請案之的内涵中，“C6-C10-芳基-CVC8-烷基’’、 “C6-C!。-芳基-CrCV烷基”及“C6-C1(r芳基-Q-C4-烷基”等詞較佳代表被甲基、乙基、丙基或丁基取代之苯基或萘基。 200932732 特佳的殘基為节基及苯乙基。在本申請案之的内涵中，“C i -c4-烷氧基” 一詞較佳代表甲氧基、乙氧基、正-丙氧基、異丙氧基、正-丁氧基、仲-丁氧基及特-丁氧基。 5 ❹ 10 15 φ 20 在本申請案之的内涵中，“CVC6-烷氧基” 一詞較佳代表甲氧基、乙氧基、正-丙氧基、異丙氧基、正-丁氧基、仲-丁氧基、特-丁氧基、戊氧基或己氧基。在本申請案之的内涵中，“c6-c10-芳氧基’’一詞較佳代表苯氧基、萘氧基、茚氧基、苟氧基或菲氧基。在本申請案之的内涵中，“C6-C10-芳基-Ci-Q-烷氧基”、“C6-C10-芳基-Q-CV烷氧基”及“C6-C1(r芳基-CVC4-烷氧基”等詞較佳代表苯醯氧基、苯乙氧基、苯丙氧基或苯丁氧基。特佳的殘基為苯醯氧基與苯乙氧基。在本申請案之的内涵中，“Q-CV烷氧基羰基”一詞較佳代表甲氧基羰基、乙氧基羰基、正-丙氧基羰基、異丙氧基羰基或丁氧基羰基。在本申請案之的内涵中，“c6-c10-芳氧基羰基”一詞較佳代表苯氧基羰基或萘氧基羰基。在本申請案之的内涵中，“C6-C10-芳基-Q-C8-烷氧基羰基”一詞較佳代表苯醯氧基羰基或苯乙氧基羰基。在本申請案之的内涵中，“C!-C6-烷基羰基”一詞較佳代表甲基羰基、乙基羰基、正-丙基羰基、異丙基羰基或丁基羰基。在本申請案之的内涵中，“c6-c10-芳基羰基”一詞較佳 15 200932732 代表苯基羰基或萘基羰基。在本申請案之的内涵中，“C6_Cl0_芳基_Ci_Q_烷基羰基”一詞較佳代表苄基羰基或笨乙基羰基。在本申請案之的内涵中，“Cl_C6_烷基羧基，，一詞較佳代 5表甲基羧基、乙基羧基、正-丙基羧基、異丙基羧基或丁基羧基。在本申請案之的内涵中’ “C6-C10-芳基羧基，，一詞較佳代表苯基叛基或萘基羧基。在本申請案之的内涵中’ “CrC6_烷基氫硫基，，一詞較佳 10 代表甲基氫硫基、乙基氫硫基、正-丙基氫硫基、異丙基氫硫基或丁基氫硫基。在本申請案之的内涵中，“c6-c10-芳基氫硫基，，一詞較佳代表苯基氫硫基或萘基氫硫基。在本申請案之的内涵中，“CVC6-烷基巯基羰基”較佳代 15 表曱基巯基羰基、乙基毓基羰基、正-丙基酼基羰基、異丙基疏基幾基或丁基魏基幾基。在本申請案之的内涵中，“Crc8-環烷基Μ基羰基”一詞較佳代表環丙基锍基羰基、環丁基酼基羰基、環戊基巯基羰基或環己基酼基羰基。 20 在本申請案之的内涵中，“c6-c10-芳基毓基羰基”一詞較佳代表苯基巯基羰基或萘基酼基羰基。在本申請案之的内涵中，“crc6-烷基巯基羧基”一詞較佳代表甲基酼基羧基、乙基巯基羧基、正-丙基巯基羧基、異丙基疏基叛基或丁基Μ基幾基。 200932732 在本申請案之的内涵中，“c6-c1(r芳基巯基羧基，，一詞較佳代表笨基疏基羧基或萘基毓基羧基。 5 10 15 ❹ 20 在本申請案之的内涵中，“CrCV烷基磺醯基”一詞較佳代表甲基磺醯基、乙基磺醯基、正-丙基磺醯基、正-丁基續醯基、仲-丁基磺醯基、特-丁基磺醯基、戊基磺醯基或己基磺醯基。在本申請案之的内涵中，“c6-c1(r芳基磺醯基，，一詞較佳代表苯基磺醯基或萘基磺醯基。在本申請案之的内涵中，“Ci-CV烷基氧硫基，，一詞較佳代表甲基氧硫基、乙基氧硫基、正-丙基氧硫基、正_丁基氧硫基、仲-丁基氧硫基或特-丁基氧硫基。在本申請案之的内涵中，“c6-c10-芳基氧硫基，，一詞較佳代表苯基氧硫基或萘基氧硫基。而且，在本發明的任擇實施例中，上所提及的取代基較佳選擇性地被下列各者取代一或多次：Ci_c6_烷基、 Ci-C6-烧氧基、Q_Cl〇_ 芳氧基、c〇2h、c〇NH2、 S〇2NH2、S〇3H、胺基、硫氫基、羥基、硝基、氰基、氟代基、氣代基、溴代基、碘代基' CF3或〇CF3。在該選擇性的取代基之定義中，CrC：6_烷基、Ci_C6_烷氧基&C6_C^_ 芳氧基較佳代表如上所提及之相同殘基。在本申請案之的内涵中，“選擇性地被取代一或多次” -3係包括無取代作用，或者以—或多個所提及之選擇性的取代基進仃單取代作用舒重取代作用0在多重取代作用之情況下’該等取代基之選擇係彼此獨立。 17 200932732 在本申請案之的内涵中，經選自下列群中的殘基取代一或多次之胺基：Ci_C6-烷基、c6-c10-芳基、c6-c10-芳基 •CrCV燒基、C6_Ci〇_芳基_Ci C6 院基、C6_Ci。芳基烷基，cvcv烷基羰基、C6_C1()-芳基羰基、crC6-烷基磺醯基 5 及C6-Cl(r芳基磺醯基，在殘基為crc6-烷基的情況下，較佳代表彼此獨立地經甲基、乙基、正_丙基、異丙基、正_丁基、仲-丁基、特-丁基、戊基或己基取代一或二次之一胺基；在殘基為c6-c10-芳基、c6-c1()-芳基_crC4-烷基、c6-c1()-芳基 -CrQ-烷基或cvCw芳基-q-CV烷基的情況下，較佳代表 10 彼此獨立地經苯基、苄基或苯乙基取代一或二次之一胺基，在殘基為CrC6-院基羰基與c6-C1(r芳基羰基的情況下，較佳代表彼此獨立地經甲基羰基、乙基羰基或苯基羰基取代一或二次之一胺基；在殘基為Ci_c6_烷基磺醯基與C6_Ci〇_ 芳基磺醯基的情況下，較佳代表彼此獨立地經甲基磺醯 I5 基、乙基續醯基或苯基績醯基取代一或二次之一胺基。在本申請案之的内涵中，“具下列化學式(II)之經二取代的胺基”一詞：CrC6-alkyl, C6-C10-aryl, C6_C10-aryl-C1-C4-alkyl, Ci-C6_alkylcarbonyl, C6-C1()-arylcarbonyl, Ci-Ce-alkylsulfonyl And C6-C10-arylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; thio; bromo; iodo; CF3 or OCF3; 5 ❹ 10 15 20 c) S03H; Amino; an amine group substituted one or more times with a residue selected from the group consisting of CrC6-alkyl, C6-C1()-aryl, C6-C1()-aryl-CrC8-alkyl , Q-C6-alkylcarbonyl 'c6-c1()-arylcarbonyl, CVC6-alkylsulfonyl and c6-c10-aryl fluorenyl; conh2; so2nh2; CONH2 or S〇2NH2 'where the amine The base functionality is substituted one or two times with a residue selected from the group consisting of Q-CV alkyl, c6-c10-aryl or Ce-CiQ-aryl-Ci-C6-alkyl, and one in two-CrC6- In the case of an alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; a sulfhydryl group; a hydroxy group; a nitro group; a cyano group, a fluorinyl group; a halogen of a chloro, bromo or a deuterated group; CF3; or hydrazine CF3; or a stereosome thereof, a pharmaceutically acceptable miscellaneous or prodrug. Another embodiment relates to the use of the above compounds for inhibiting fatty acid guanamine hydrolase (FAAH) and for the treatment of medical conditions which are positively affected by FAAH inhibition. In particular, in the journal of Pacher et al., corpse Wm (10) Ζ.^ν· "58th 389-462 (2_ years), the use of the above-mentioned compounds in the treatment of the diseases and medical conditions mentioned is particularly pointed out. Related to a pharmaceutical composition comprising a compound of the above formula (I) or a-enantiomer thereof, a pharmaceutically acceptable salt or a precursor drug, and related to administration by pharmaceutically active A method of treating a disease and a medical condition mentioned above, a compound of the above formula (1), an enantiomer thereof, a pharmaceutically acceptable salt of 13, 200932732 or a prodrug. In the meaning of the present application, the term "crc4-alkyl" preferably denotes fluorenyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl and tert-butyl. In the meaning of the present application, the term "CrC6-alkyl" preferably denotes fluorenyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, Butyl or hexyl. In the meaning of the present application, the term "crc18-alkyl" preferably represents methyl, ethyl, or Propyl, isopropyl, n-butyl, sec-butyl, tert-butyl 10, pentyl, hexyl, octyl, decyl, dodecyl, tetradecyl and octadecyl. In the meaning of the present application, the term "unsaturated or polyunsaturated c2-c18-alkylene" preferably represents vinyl, n-propenyl, isopropenyl, n-butenyl, sec- Butenyl, tert-butenyl, pentenyl, hexenyl, 15 octenyl, nonenyl, dodecyl, tetradecyl, octadecyl, dodecadiene In the meaning of the present application, the term "c3-c8-cycloalkyl" preferably represents cyclopropyl, cyclobutyl, cyclopentyl or In the context of the present application, the term c6-c10-aryl preferably represents phenyl 20, cyclopentadienyl, indenyl, indanyl, isoindolyl, chroman. , naphthyl, anthracenyl, fluorenyl, phenanthryl or anthracenyl. In the meaning of the present application, "C6-C10-aryl-CVC8-alkyl", "C6-C!-aryl" -CrCV alkyl" and "C6-C1 (r-aryl-Q-C4-alkyl) are preferably represented by a phenyl or naphthyl group substituted with a group, an ethyl group, a propyl group or a butyl group. 200932732 A particularly preferred residue is a benzyl group and a phenethyl group. In the meaning of the present application, "C i -c4-alkoxy" The term preferably represents methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy and tert-butoxy. 5 ❹ 10 15 φ 20 In the meaning of the present application, the term "CVC6-alkoxy" preferably represents methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy. , in the meaning of the present application, the term "c6-c10-aryloxy" preferably represents phenoxy, naphthyloxy, decyloxy. , methoxy or phenoxy. In the meaning of the present application, "C6-C10-aryl-Ci-Q-alkoxy", "C6-C10-aryl-Q-CV alkoxy" and "C6-C1 (r aryl) The term "-CVC4-alkoxy" preferably denotes phenoxy, phenethyloxy, phenylpropoxy or phenylbutoxy. The most preferred residues are benzoinoxy and phenethyloxy. In the context of the application, the term "Q-CV alkoxycarbonyl" preferably denotes methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl or butoxycarbonyl. In the meaning of the present application, the term "c6-c10-aryloxycarbonyl" preferably denotes phenoxycarbonyl or naphthyloxycarbonyl. In the meaning of the present application, "C6-C10-aryl- The term "Q-C8-alkoxycarbonyl" preferably represents phenylhydrazineoxycarbonyl or phenylethoxycarbonyl. In the meaning of the present application, the term "C!-C6-alkylcarbonyl" is preferably represented. Methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl or butylcarbonyl. In the meaning of the present application, the term "c6-c10-arylcarbonyl" is preferably 15 200932732 represents phenyl Carbonyl or naphthylcarbonyl. In the context of the present application In the meaning, the term "C6_Cl0_aryl_Ci_Q_alkylcarbonyl" preferably represents a benzylcarbonyl group or a phenoethylcarbonyl group. In the meaning of the present application, "Cl_C6_alkylcarboxy," is a preferred term. 5 represents methylcarboxy, ethylcarboxy, n-propylcarboxy, isopropylcarboxy or butylcarboxy. In the context of the present application 'C6-C10-arylcarboxy, the term preferably represents benzene a radical or a naphthylcarboxy group. In the context of the present application, 'CrC6_alkyl thiol, the term preferably 10 represents methyl thio, ethyl thio, n-propyl hydride. Sulfhydryl, isopropylthiol or butylhydrogenthio. In the meaning of the present application, "c6-c10-arylhydrosulfanyl," preferably represents phenylhydrosulfanyl or naphthyl Hydrogenthio. In the meaning of the present application, "CVC6-alkylmercaptocarbonyl" preferably represents 15 fluorenylcarbonyl, ethyl fluorenylcarbonyl, n-propyl fluorenylcarbonyl, isopropyl sulfhydryl In the meaning of the present application, the term "Crc8-cycloalkylfluorenylcarbonyl" preferably represents cyclopropylcarbonylcarbonyl, cyclobutylhydrazinocarbonyl. Cyclopentylcarbonylcarbonyl or cyclohexylfluorenylcarbonyl. 20 In the meaning of the present application, the term "c6-c10-aryldecylcarbonyl" preferably denotes phenylmercaptocarbonyl or naphthylfluorenylcarbonyl. In the meaning of the present application, the term "crc6-alkylmercaptocarboxy" preferably represents methylmercaptocarboxy, ethylmercaptocarboxy, n-propyldecylcarboxy, isopropyl thiol or butyl. In the meaning of the present application, "c6-c1 (r aryl fluorenyl carboxy, the term preferably represents a phenyl group or a naphthyl fluorenyl group. 5 10 15 ❹ 20 In the meaning of the present application, the term "CrCV alkylsulfonyl" preferably represents methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, n-butyl fluorenyl, secondary. - butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl or hexylsulfonyl. In the meaning of the present application, "c6-c1 (rarylsulfonyl,) preferably represents phenylsulfonyl or naphthylsulfonyl. In the meaning of the present application, "Ci -CV alkyl oxythio, the term preferably represents methyl oxythio, ethyl oxythio, n-propyl oxythio, n-butyl oxythio, sec-butyl oxythio or In the meaning of the present application, "c6-c10-aryloxythio," preferably means phenyloxythio or naphthyloxythio. In an optional embodiment of the invention, the substituents mentioned above are preferably optionally substituted one or more times by: Ci_c6-alkyl, Ci-C6-alkoxy, Q_Cl〇_ aryloxy, C〇2h, c〇NH2, S〇2NH2, S〇3H, amine group, sulfhydryl group, hydroxyl group, nitro group, cyano group, fluoro group, gas group, bromo group, iodo group 'CF3 or 〇 CF3. In the definition of the selective substituent, CrC: 6-alkyl, Ci_C6-alkoxy & C6_C^_ aryloxy preferably represents the same residue as mentioned above. In the connotation, "selectively replaced one or more times" -3 Series Including unsubstituted, or accepting mono-substitution with or - a plurality of the mentioned substituents, the single-substitution, the substitution of the substituents, in the case of multiple substitutions, 'the choice of such substituents is independent of each other. 17 200932732 In the meaning of the present application, one or more amine groups are substituted with a residue selected from the group consisting of Ci_C6-alkyl, c6-c10-aryl, c6-c10-aryl•CrCV alkyl, C6_Ci〇_aryl_Ci C6, C6_Ci. arylalkyl, cvcv alkylcarbonyl, C6_C1()-arylcarbonyl, crC6-alkylsulfonyl 5 and C6-Cl (rarylsulfonyl) In the case where the residue is crc6-alkyl, it preferably represents independently of each other via methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, The pentyl or hexyl group is substituted with one or two amine groups; the residue is c6-c10-aryl, c6-c1()-aryl-crC4-alkyl, c6-c1()-aryl-CrQ- In the case of an alkyl group or a cvCw aryl-q-CV alkyl group, it is preferred that 10 independently of one another, one or two amine groups are substituted by a phenyl group, a benzyl group or a phenethyl group, and the residue is a CrC6-house. In the case of a carbonyl group and a c6-C1 (r aryl carbonyl group) Preferably, one or two amine groups are substituted by methylcarbonyl, ethylcarbonyl or phenylcarbonyl, independently of each other; in the case where the residue is Ci_c6-alkylsulfonyl and C6_Ci〇_arylsulfonyl Preferably, the one or the second amine group is substituted by methylsulfonium I5 group, ethyl fluorenyl group or phenyl fluorenyl group independently of each other. In the meaning of the present application, "the following chemical formula ( II) The term "disubstituted amine":

其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與 20 CVC6-烷基，及其中化學式（II)中的亞曱基可選擇性地被Wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and 20 CVC 6-alkyl, and the fluorenyl group in the formula (II) is optionally

CrCV炫基、氟代基或氣代基取代一或二次；及具下列化學式(II)之經二取代的胺基較佳代表哌啶基、哌嗪基、吡洛烷基、嗎嚇·基、N-甲基0底嗓或2,2,6,6-四甲基《底咬基。 200932732 5 ❹ 10 15 ⑩ 20 在本申請案之的内涵中，C〇NH2或so2nh2，其中該胺基B能度被選自CVCV烷基、c6-C10-芳基、c6-c10-芳基 -C1-C4-院基或C6_Ci〇_芳基Ci Q烷基的殘基取代一次或多次，及其中在—種經二-C〗-C6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；係較佳由下列各者所衍生的個別殘基所代表：N N二甲基醯胺、N甲基酿胺、N-乙基醯胺、N_苯基醯胺、NN二甲基磺醯胺、N_ 甲基磺醯胺、N-乙基磺醯胺及N_苯基磺醯胺。在胺基官能度經烷基二取代之情況下，二殘基結合形成5或6員環亦為一較佳的任擇方式。該胺基官能度的實例包括但不限於吡嘻燒與派。定。在本申請案之的内涵中，“一種由至多1〇個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次.Q-CV烷基；q-Q-烷氧基；COOH ; S〇3H ; CONHJ S〇2NH2; CONH2 或 S〇2NH2，其中該胺基官能度被選自Q-CV烷基、Q-Cht芳基或c6_Ci〇_芳基_Ci_c4_ 烷基的殘基取代一次或多次，及其中在—種經二_Ci_C6烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成 5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基_ Q-CV烷基、C6-C1(r芳基、C6-C10-芳基-Q-Cr烷基、 CrCV烷基羰基、Q-Cur芳基羰基、Ci_C6烷基磺醯基及 CVQq-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基，亂代基，邊代基，礙代基；CF3或〇cf3“一詞，，，較佳由一種由至多10個原子組成之含有1至4個選自氮、氧或硫的 19 200932732 雜原子之飽和、不飽和或芳族雜環式環系統所代表由至多10個原子組成之飽和、*飽和或芳麵環的較佳實例包括但不限於：苯並料、苯並料、苯_吩、苯並七坐、苯並噻唑、咔唑、噌啉、戴奥辛(dioxi - 一天規、二。夫戊 5 10 15 20 烧、m唤、二tn茂燒”夫喃、嗦嗤、咪唑啉、咪唑烷、吲哚、吲哚啉、吲嗪、吲唑、異吲哚、異喹啉、異呋唑、異噻唑、嗎啉、萘啶、呋唑、呋二唑、The CrCV thiol, fluoro or ke group is substituted one or two times; and the disubstituted amino group of the following formula (II) preferably represents piperidinyl, piperazinyl, pyrrolidinyl, or Base, N-methyl 0 base or 2,2,6,6-tetramethyl "bottom bite. 200932732 5 ❹ 10 15 10 20 In the meaning of the present application, C〇NH2 or so2nh2, wherein the amine B energy is selected from the group consisting of CVCV alkyl, c6-C10-aryl, c6-c10-aryl- Substituting a residue of a C1-C4-homogene or a C6_Ci〇_aryl Ci Q alkyl group one or more times, and wherein in the case of an amine functional group substituted with a di-C-C6-alkyl group, The alkyl residue may be combined to form a 5 or 6 membered ring; preferably represented by individual residues derived from: NN dimethyl decylamine, N methyl urethane, N-ethyl decylamine N-phenyldecylamine, NN dimethylsulfonamide, N-methylsulfonamide, N-ethylsulfonamide and N-phenylsulfonamide. In the case where the amino functionality is disubstituted by an alkyl group, it is also a preferred alternative to combine the two residues to form a 5 or 6 membered ring. Examples of such amine functionality include, but are not limited to, pyridoxine and pie. set. In the meaning of the present application, "a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 1 atom, which is optionally substituted by one or more of the following. Q-CV alkane a group; qQ-alkoxy; COOH; S〇3H; CONHJ S〇2NH2; CONH2 or S〇2NH2, wherein the amine functionality is selected from Q-CV alkyl, Q-Cht aryl or c6_Ci〇_芳Substituting a residue of a base —Ci_c 4 —alkyl one or more times, and wherein, in the case of an amine functionality substituted with a di-Ci—C 6 alkyl group, the alkyl residue may be combined to form a 5 or 6 membered ring; Amine; one or more amino groups substituted with a residue selected from the group consisting of _Q-CV alkyl, C6-C1 (r aryl, C6-C10-aryl-Q-Cr alkyl, CrCV alkane Carbonyl group, Q-Cur arylcarbonyl group, Ci_C6 alkylsulfonyl group and CVQq-arylsulfonyl group; sulfhydryl group; hydroxyl group; nitro group; cyano group; fluoro group, chaotic group, aryl group, hindr The term "CF3 or 〇cf3", preferably consists of a saturated, unsaturated or aromatic impurity consisting of up to 10 atoms containing from 1 to 4 of the 2009 20093232 heteroatoms selected from nitrogen, oxygen or sulfur. Ring ring system Preferred examples of a saturated, *saturated or aromatic ring having a composition of more than 10 atoms include, but are not limited to, benzo, benzo, benzophenone, benzo-7, benzothiazole, carbazole, porphyrin, Dioxin (dioxi - one day, two. Fu 5 10 15 20 burning, m calling, two tn roasting), sputum, imidazoline, imidazolidine, hydrazine, porphyrin, pyridazine, carbazole, Isoindole, isoquinoline, isofurazol, isothiazole, morpholine, naphthyridine, furazol, furadiazole,

呋噻唑、呋噻唑烷、呋嗪、呋二嗪、吩嗪、吩噻嗪吩呋嗪、酞嗪、哌嗪、哌啶、蝶啶、嘌々、吡喃、吡嗪、吡唑、吡唑啉、吡唑烷、噠嗪、吡啶、嘧啶、吡咯、吡咯烷£、吡咯啉、喹啉、喹呋啉、喹唑啉、喹嗪、四氫呋喃、四嗪、四唑、噻吩、噻二嗪、噻二唑、噻***、噻嗪、噻唑、硫嗎啉、噻萘、噻喃、三嗪、***與三噻烷，及其等所有的異構構形。該等雜環可被下列各者取代一或多次：Ci_c^ 烧基；Ci-CV院氧基；COOH ; so3h ; conh2 ; S02NH2 ;Furthiazole, furadiazolidine, furazine, furadiazine, phenazine, phenothiazine, phenothiazine, pyridazine, piperazine, piperidine, pteridine, indole, pyran, pyrazine, pyrazole, pyrazole Porphyrin, pyrazolidine, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolidine, pyrroline, quinoline, quetialine, quinazoline, quinolizine, tetrahydrofuran, tetrazine, tetrazole, thiophene, thiadiazine, Thiadiazole, thiatriazole, thiazine, thiazole, thiomorpholine, thionaphthalene, thiopyran, triazine, triazole and trithiane, and all other isomeric forms thereof. The heterocyclic rings may be substituted one or more times by the following: Ci_c^ alkyl; Ci-CV alkoxy; COOH; so3h; conh2; S02NH2;

CONH2或SC^NH2 ’其中該胺基官能度被選自Ci C6院基、 CVC1 〇-芳基或q_C i〇_芳基_c】_院基的殘基取代—次或多次，及其中在一種經二_Cl_C6_烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：Ci_c6烧基、 c6-c10-芳基、c6_Ci(r芳基_c广c4_烧基、Ci CV烧基羰基、 CVCur芳基羰基、Ci_Q_烷基磺醯基及c6_Ci〇芳基磺醯基；硫氫基、羥基、硝基、氰基、氟代基、氣代基、溴代基、碘代基、CF3或OCF3。特佳的選擇性取代基為曱基、 20 200932732 甲氧基、胺基、羥基、硝基、氰基、氟代基、氯代基、塢代基、碘代基、cf3及〇cf3。 5 10 15 ❹ 20 由至多10個原子組成之飽和、不飽和或芳族雜環式環系統之最佳實例，包括2-n比咬、比咬及4-n比咬，該三者皆選擇性地被一或多個選自曱基、胺基、氟代基、氣代基或 CF3之殘基取代；及包括N-連結型吡咯，其選擇性地被一或多個選自曱基、胺基、氟代基、氣代基或Cf3之殘基取代。在本發明的另一實施例中，Ri至R5中之二或多者可結合形成稠合的飽和、不飽和或芳族同環或雜環系統。該等環系統的實例包括但不限於：苯並咪唑、苯並呋鳴、苯並 °塞吩、苯並吱唑及苯並嗔唑。在上述的化學式(I)中，R1至R5較佳彼此獨立地代表：氫；羥基；CONH2 or SC^NH2' wherein the amino functionality is substituted by a residue selected from the group consisting of Ci C6, CVC1 〇-aryl or q_C i〇_aryl_c]-, or a plurality of times, and In the case of an amine functionality substituted with a di-Cl_C6-alkyl group, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; one or more substituted with a residue selected from the group consisting of Amino group: Ci_c6 alkyl, c6-c10-aryl, c6_Ci (raryl_c wide c4_alkyl, Ci CV alkylcarbonyl, CVCur arylcarbonyl, Ci_Q_alkylsulfonyl and c6_Ci〇 Arylsulfonyl; sulfhydryl, hydroxy, nitro, cyano, fluoro, carbyl, bromo, iodo, CF3 or OCF3. Particularly preferred substituents are fluorenyl, 20 200932732 methoxy, amine, hydroxy, nitro, cyano, fluoro, chloro, dock, iodo, cf3 and 〇cf3. 5 10 15 ❹ 20 saturated with up to 10 atoms Preferred examples of unsaturated, aromatic or aromatic heterocyclic ring systems, including 2-n specific bites, specific bites, and 4-n specific bites, are all selectively selected from one or more selected from the group consisting of sulfhydryl groups and amines. Base, fluoro group, gas group or CF3 Substituent substitution; and includes N-linked pyrrole, which is optionally substituted with one or more residues selected from the group consisting of sulfhydryl, amine, fluoro, carbyl or Cf3. Another embodiment of the invention In one embodiment, two or more of Ri to R5 may combine to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system. Examples of such ring systems include, but are not limited to, benzimidazole, benzofuran In the above formula (I), R1 to R5 are preferably independently of each other: hydrogen; hydroxy;

Ci-C6-烧基、c6-c1()-芳基、CrQ-烧氧基、C6-Ci〇-芳氧基、C6-C1(r芳基-CKC6-烷氧基、q-Q-烷基羧基、 CVCur芳基羧基、CrCV烧基續醯基、c6-Cht芳基罐醯基’其中各者選擇性地被下列各者取代一次或多次：CrCV 烧基、CrC6-烧氧基、胺基、crC6-烧基胺基、二-CrC6- 烷基胺基、羥基、氟代基、氯代基、溴代基、氰基、CF3 或 OCF3 ; 胺基；經選自Ci-CV烧基、C6-C10-芳基的殘基取代一或多次之胺基； 21 200932732 1-°比洛基、2-"比咯基或3-°比略基，其選擇性地被選自 Q-C6-烷基，胺基，氟代基，氣代基或CF3之一或多個殘基取代；具下列化學式(II)之一種經二取代的胺基：Ci-C6-alkyl, c6-c1()-aryl, CrQ-alkoxy, C6-Ci〇-aryloxy, C6-C1 (raryl-CKC6-alkoxy, qQ-alkylcarboxyl , CVCur aryl carboxyl group, CrCV alkyl group, c6-Cht aryl aryl group, each of which is optionally substituted one or more times by: CrCV alkyl, CrC6-alkoxy, amine , crC6-alkylamino, di-CrC6-alkylamino, hydroxy, fluoro, chloro, bromo, cyano, CF3 or OCF3; amine group; selected from Ci-CV alkyl, The residue of a C6-C10-aryl group is substituted with one or more amine groups; 21 200932732 1-°Biro, 2-"birotyl or 3-°pyranyl, which is selectively selected from Q Substituted with one or more residues of -C6-alkyl, amine, fluoro, carbyl or CF3; a disubstituted amino group of the following formula (II):

55

其中〇代表0或1 ’而W代表氧、CH2或NR6，R6係選自氫與Ci-CV烷基，及其中化學式(π)中的亞甲基可選擇性地被^^6-院基、氟代基或氣代基取代一或二次； CONH2 ; 10 15 so2nh2 ； CONH2或S〇2NH2，其中該胺基官能度被選自Ci_Q烷基或C6-C1()-芳基的殘基取代一或二次；氟代基；氣代基；溴代基；Wherein 〇 represents 0 or 1 ' and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and Ci-CV alkyl, and the methylene group in the chemical formula (π) thereof may be selectively selected from the group Substituting one or two times with a fluoro or a gas group; CONH2; 10 15 so2nh2 ; CONH2 or S〇2NH2, wherein the amino functionality is selected from a residue of Ci_Q alkyl or C6-C1()-aryl Substituting one or two; fluoro group; gas group; bromo group;

CF3 ;或 0CF3。在上述的化學式(1)中，之一或多者更佳代表氫、氟或氯。R1或R5更佳代表氫或氟。Rlw5最佳代表氣。在上述的化學式⑴中，RljLR>之一或多者更佳代表經基；Cl-(V院氧基、CVCV芳氧基、C6_Ci。芳基_Ci_c6 烧氧基、Cl々烧錢基、c6-cv芳基幾基、Cl-C6-院基橫醯基c6-c10-芳基續醯基，其中各者選擇性地被下列各 22 20 200932732 5CF3; or 0CF3. In the above chemical formula (1), one or more of them more preferably represent hydrogen, fluorine or chlorine. R1 or R5 more preferably represents hydrogen or fluorine. Rlw5 is the best representative of gas. In the above chemical formula (1), one or more of RljLR> more preferably represents a trans group; Cl-(V-oxyl, CVCV aryloxy, C6_Ci. aryl_Ci_c6 alkoxy, Cl 々钱, c6 -cv aryl yl, Cl-C6-homo-based fluorenyl c6-c10-aryl fluorenyl, each of which is selectively selected by the following 22 20 200932732 5

10 者取代一或多次：CVC6-烷基、crc6-烷氧基、胺基、 CVC4-烷基胺基、二-q-cv烷基胺基、選擇性地被CVCV烷基或C6-C1()-芳基取代一或二次之c〇NH2或so2nh2、羥基、氟代基、氯代基、溴代基、氰基、cf3或OCF3。 R2、R3或R4更佳代表羥基；Ci_C6_烧氧基、C6_ClQ_芳氧基、C6-C1()-芳基-CrC：6-烧氧基，其中各者選擇性地被下列各者取代一或多次：Ci-CV烷基、CrCV烷氧基、胺基、 Cj-Cr烷基胺基、二-q-Q-烷基胺基、選擇性地被CVC6-烧基或（VCiQ-芳基取代一或二次之c〇NH2或S〇2NH2、羥基、說代基、氣代基或演代基。在上述的化學式(I)中，R1至R5中之一或多者更佳代表胺基，經選自（^-0!6-烧基、C6-C1()-芳基的殘基取代一或多次之胺基；或具下列化學式(II)之一種經二取代的胺基：Substituting one or more times: CVC6-alkyl, crc6-alkoxy, amine, CVC4-alkylamino, bis-q-cv alkylamino, optionally CVCV alkyl or C6-C1 ()-aryl substituted one or two of c〇NH2 or so2nh2, hydroxy, fluoro, chloro, bromo, cyano, cf3 or OCF3. R2, R3 or R4 more preferably represents a hydroxyl group; Ci_C6_alkoxy, C6_ClQ_aryloxy, C6-C1()-aryl-CrC: 6-alkoxy, each of which is optionally substituted by One or more times: Ci-CV alkyl, CrCV alkoxy, amine, Cj-Cr alkylamine, bis-qQ-alkylamine, optionally CVC6-alkyl or (VCiQ-aryl) Substituting one or two of c〇NH2 or S〇2NH2, a hydroxyl group, a hydrazino group, a gas group or a deuteration group. In the above formula (I), one or more of R1 to R5 are more preferably an amine. a dibasic amino group substituted by one or more substituents selected from the group consisting of (^-0!6-alkyl, C6-C1()-aryl; or a disubstituted amino group of the following formula (II) :

ViVi

15 ❹ ° (II) 其中0代表0或1，而W代表氧、CH2或NR6，R6係選自氫與CrC4-烷基，及其中化學式(π)中的亞甲基可選擇性地被Ci-C4-烧基、氟代基或氯代基取代一或二次。 R2、R3或R4中之一者更佳代表胺基；被選自CrC6-烷基、CVCι〇-芳基的殘基取代一或二次之胺基；或具下列化學式(II)之一種經二取代的胺基：15 ❹ ° (II) wherein 0 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and CrC 4 -alkyl, and the methylene group in the formula (π) thereof is optionally Ci The -C4-alkyl, fluoro or chloro group is substituted one or two times. One of R2, R3 or R4 more preferably represents an amine group; an amine group substituted one or two times with a residue selected from the group consisting of CrC6-alkyl or CVCι〇-aryl; or one of the following chemical formula (II) Disubstituted amine groups:

其中〇代表0或1，而W代表氧、ch24NR6，R6係選自 23 20 200932732 氫與Ci-C4-烷基，及其中化學式(II)中的亞曱基可選擇性地被Crc4-烷基、氟代基或氣代基取代一或二次。更佳，在上述的化學式(I)中，其中η代表0 ; m代表0、 1、2、3、4、5或6 ;及Y代表C3-C6-環烧基或c6_Cl〇_芳 5 基’其中各者選擇性地被下列各者取代一或多次： a) Ci_C6-烧基、C6-C10-芳基、C6-C10-芳基烧基、Wherein 〇 represents 0 or 1, and W represents oxygen, ch24NR6, and R6 is selected from the group consisting of 23 20 200932732 hydrogen and Ci-C4-alkyl, and wherein the fluorenyl group in the formula (II) is optionally Crc4-alkyl The fluoro group or the gas group is substituted one or two times. More preferably, in the above formula (I), wherein η represents 0; m represents 0, 1, 2, 3, 4, 5 or 6; and Y represents C3-C6-cycloalkyl or c6_Cl〇_aryl 5 ' Each of them is optionally substituted one or more times by: a) Ci_C6-alkyl, C6-C10-aryl, C6-C10-arylalkyl,

Ci-C6_烧氧基、Ce-CiQ-芳氧基、C6_Ci〇-芳基-CrCj-烧氧基，其中各者選擇性地被下列各者取代一次或多次： CVC6-烷基；Q-CV烷氧基；COOH ; CONH2 ; © 10 S02NH2 ;被CrCV烷基或C6-C10-芳基取代一或二次之 conh2或so2nh2 ; so3h ;胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、c6-c10-芳基、 c6-c10-芳基-CrCV烷基、（VC6-烷基羰基、c6-c1(r芳基羰基、crc6-烷基磺醯基及c6-c1G-芳基磺醯基；硫氫 15 基；羥基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；CF3或OCF3 ; 或被： ο b) 羥基；硫氫基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；CF3 ; 〇CF3 ; co2h ; so3h ; conh2 ; 20 S〇2NH2 ; conh2或so2nh2，其中該胺基官能度被選自 CrC6-烧基、C6-C10-芳基或c6-C10-芳基-CrC4-烧基的殘基取代一次或多次’及其中在一種經二烷基取代的胺基官能度之情況下、該烷基殘基可結合而形成5或6員環；胺基，被C1 -C6_烧基或本基取代一或多次之胺基；具下列 24 200932732 化學式(II)之一種經二取代的胺基： /~ΛCi-C6_alkoxy, Ce-CiQ-aryloxy, C6_Ci〇-aryl-CrCj-alkoxy, wherein each is optionally substituted one or more times by: CVC6-alkyl; Q -CV alkoxy; COOH; CONH2; © 10 S02NH2; one or two of conh2 or so2nh2 substituted by CrCV alkyl or C6-C10-aryl; so3h; amine; substituted with a residue selected from the group below One or more amine groups: crc6-alkyl, c6-c10-aryl, c6-c10-aryl-CrCV alkyl, (VC6-alkylcarbonyl, c6-c1 (rarylcarbonyl, crc6-alkane) Sulfosulfonyl and c6-c1G-arylsulfonyl; sulfhydryl 15 ; hydroxy; nitro; cyano; fluoro; thio; bromo; iodo; CF3 or OCF3; : ο b) hydroxy; sulfhydryl; nitro; cyano; fluoro; valence; bromo; iodo; CF3; 〇CF3; co2h; so3h; conh2; 20 S〇2NH2; conh2 or So2nh2, wherein the amino functionality is substituted one or more times by a residue selected from the group consisting of CrC6-alkyl, C6-C10-aryl or c6-C10-aryl-CrC4-alkyl; and in a dioxane In the case of a substituted amino function, the alkyl residue can be combined to form 5 or 6 members. Amino group, an amine group substituted one or more times by a C1 -C6-alkyl group or a radical; having the following 24 200932732 a disubstituted amino group of formula (II): /~Λ

(II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自 5 氫與CVCr烷基，及其中化學式(II)中的亞甲基可選擇性地被CVCV烷基、氟代基或氣代基取代一或二次；或被： c)一種由至多10個原子組成之飽和、不飽和或芳族雜 €> 環式環系統，其選擇性地被下列各者取代一或多次： crc6-烷基；CrC6-烷氧基；COOH ; CONH2 ; 10 so2nh2 ;被。广(：6-烷基或c6-c10-芳基取代一或二次之 conh2或so2nh2 ; so3h ;胺基；經選自下列群中的殘基取代一或多次之胺基：CVCV烷基、C6-C10-芳基、 C6-C10-芳基-Cl_c4_烷基、crc6-烷基羰基、C6_Cl0_芳基幾基、CrCV烷基磺醯基及C6-Ch)-芳基磺醯基；硫氫 15 基；經基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；CF3或〇cf3。更佳η代表0 ; m代表0或1 ;及Y代表一個苯基、丨-萘基2-萘基、2-吡啶基、3-吡啶基或4-吡啶基環系統。在該方面，更佳Y被下列各者取代一或多次：CrC4-烷 20基’苯基；Cl-C4-烷氧基；羥基；氟代基；氣代基；溴代基，CF3 ; 〇CF3 ;選擇性地被Cl_C4_烷基取代一或二次之 CONH2或S〇2NH2 ’其中該等選擇性心心烷基殘基可結合而形成5或6員環；或胺基。 25 200932732 在該方面，又更佳„!代表〇，及γ代表被羥基、氟代基、氣代基或溴代基取代一或二次之苯基。在該方面，最佳m代表0 ;及γ代表苯基，其在4_位置被氟代基取代、在4-位置被氣代基取代、在2_與4_位置被氟代 5 基取代、在2_與4-位置被氯代基取代或在4-位置被苯基取代。在上述的化學式(I)中，特佳111為〇 ; 11為〇 ; γ代表被氟代基、氣代基或漠代基取代一或二次之苯基；及R2至R4中之任一者代表OR7，其中R7係選自氫與Ci_C4烷基。在上述的化學式(I)中，亦為非常佳者係瓜為〇 ; η為〇 ; ❹ 10 Υ代表在4_位置被氟代基取代、在4-位置被氯代基取代、在 2-與4-位Ϊ被H代基取代或在2_與4_位£被減基取狀苯基’及R2至R4中之任一者代表〇r7，其中r7係選自氯與 CVC4-烷基在上述的化學式⑴中，亦為非常佳者係〇為〇 ; ; 15 Y代表被氟代基、氣代基或溴代基取代一或二次之苯基，及 R3或者R3與R4代表羥基。在上述的化學式附，亦為非常佳者係; n細； ◎ Y代表在4-位置被氟代基取代、在4_位置被氣代基取代、在 2-與4-位置被氟代基取代或在2•與4·位置被氣代基取代之 20 苯基，及R3或者R3與R4代表羥基在上述的化學式(I)中，特行佳111為0，η為ο ; Y代表被氟代基、氯代基或》臭代基取代—或二次之苯基；r^r4中之任-者代表OR7 ’其中R7係選自氫與Ci<v烧基；^代表氫或氟。 26 200932732 在上述的化學式(I)中，特佳〇!為〇 ; ; γ代表在4_ 位置被氟代基取代、在4_位置被氣代基取代、在與4位置被氟代基取代或在2-與4-位置被氣代基取代之苯基；R2至 R4中之任一者代表OR7’其中r7係選自氫與Ci C4烷基；及 5 R1代表氫或氟。在上述的化學式(I)中，特佳〇1為0 ; η為〇 ; γ代表被氟代基、氣代基或溴代基取代一或二次之苯基；R3或者R3與 R4代表經基；及R1代表氫或氟。 ® 在上述的化學式⑴中，特佳m為〇 ; η為〇 ; γ代表在4- 1〇位置被氟代基取代、在4-位置被氣代基取代、在2-與4-位置被氟代基取代或在2-與4·位置被氣代基取代之苯基；R3或 ' 者r3與r4代表羥基；及r1代表氫或氟。而且’在上述的化學式⑴中，亦為較佳者係η為〇，m 為〇或1，Y代表C6_C10-芳基及較佳為苯基、苄基、苯乙基、 15 笨丙基、笨丁基或苯己基，其選擇性地被下列各者取代一或多次： ❹ aXVCV烧基、c3_C8_環院基、C6_Ci『芳基、C6_Ci〇_芳基-Q-CV烷基、CrC6_烷氧基、C6_Ci〇_芳氧基、C6_Ci〇芳基 -cvc8-烧敦基、經基、c〇2H、Ci_C6_院氧基幾基、C6_Ci〇· 20芳氧基羰基、C6-Ci〇-芳基-cvcv烷氧基羰基、CrC6-烷基羰基、c6-c1(r芳基羰基、C6_Ci〇_芳基_Ci_C8_烧基羰基、CiC6_ 烷基羧基、c6-c1(r芳基羧基、Crc6_烷基氫硫基、c6_Ci(r 芳基氫硫基、Ci-C6-烷基巯基羰基、c3-c8-環烷基巯基羰基、cvcv芳基巯基羰基、CrC6-烷基酼基羧基、c6_Ci〇_ 27 200932732 芳基酼基羧基、CrCV烷基磺醯基、CVCio-芳基磺醯基、(II) wherein 〇 represents 0 or 1, and W represents oxygen, CH2 or NR6, and R6 is selected from the group consisting of 5 hydrogen and CVCr alkyl, and wherein the methylene group in the formula (II) is optionally CVCV alkyl, a fluoro or a gas group substituted one or two times; or by: c) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, optionally selected by Substituted one or more times: crc6-alkyl; CrC6-alkoxy; COOH; CONH2; 10 so2nh2; Wide (6-alkyl or c6-c10-aryl substituted one or two conh2 or so2nh2; so3h; amine group; amine group substituted one or more times with a residue selected from the group consisting of CVCV alkyl , C6-C10-aryl, C6-C10-aryl-Cl_c4_alkyl, crc6-alkylcarbonyl, C6_Cl0_aryl, CrCV alkylsulfonyl and C6-Ch)-arylsulfonyl Sulfhydryl 15 group; trans group; nitro; cyano; fluoro; chloro; bromo; iodo; CF3 or 〇cf3. More preferably, η represents 0; m represents 0 or 1; and Y represents a phenyl, indenyl-naphthyl 2-naphthyl, 2-pyridyl, 3-pyridyl or 4-pyridyl ring system. In this aspect, more preferably Y is substituted one or more times by the following: CrC4-alkano 20-yl-phenyl; Cl-C4-alkoxy; hydroxy; fluoro; aldehyde; bromo, CF3; 〇CF3; CONH2 or S〇2NH2' optionally substituted one or two times with Cl_C4_alkyl wherein the selective core alkyl residues may combine to form a 5 or 6 membered ring; or an amine group. 25 200932732 In this respect, it is more preferred that „! stands for 〇, and γ represents a phenyl group substituted one or two times with a hydroxyl group, a fluoro group, an oxyl group or a bromo group. In this respect, the optimum m represents 0; And γ represents a phenyl group which is substituted by a fluoro group at the 4 position, a gas group at the 4-position, a fluoro 5 group at the 2_ and 4_ positions, and a chlorine at the 2 and 4 positions. Substituted or substituted by a phenyl group at the 4-position. In the above formula (I), particularly preferably 111 is hydrazine; 11 is hydrazine; γ represents one or two substituted by fluoro, a gas or a thio group. The phenyl group; and any one of R2 to R4 represents OR7, wherein R7 is selected from the group consisting of hydrogen and Ci_C4 alkyl. In the above formula (I), it is also very good, the melon is 〇; η is 〇 ; ❹ 10 Υ represents a fluoro group at the 4_ position, a chloro group at the 4-position, a H group at the 2- and 4-positions, or a subtraction at the 2_ and 4_ positions. The phenyl group and any one of R2 to R4 represent 〇r7, wherein r7 is selected from the group consisting of chlorine and CVC4-alkyl group in the above formula (1), and is also a very preferred one; 15 15 represents Substituted by a fluoro, a gas or a bromo group Or a second phenyl group, and R3 or R3 and R4 represent a hydroxyl group. In the above chemical formula, it is also a very good one; n is fine; ◎ Y represents a 4-position substituted by a fluoro group, and is at a 4 position. a gas group substituted, a 20 phenyl group substituted with a fluoro group at the 2- and 4-positions or a gas group at the 2 and 4 positions, and R3 or R3 and R4 represent a hydroxyl group in the above formula (I) In the middle, the special line 111 is 0, η is ο; Y represents a phenyl group substituted by a fluoro group, a chloro group or a odor group or a second phenyl group; any of r^r4 represents OR7 'where R7 It is selected from the group consisting of hydrogen and Ci<v alkyl; ^ represents hydrogen or fluorine. 26 200932732 In the above formula (I), 特〇 is 〇; ; γ represents substitution at the 4_ position by a fluoro group, at 4_ a phenyl group substituted with a gas group, substituted with a fluoro group at the 4-position or substituted with a gas group at the 2- and 4-positions; any of R2 to R4 represents OR7' wherein the r7 is selected from hydrogen And Ci C4 alkyl; and 5 R1 represents hydrogen or fluorine. In the above formula (I), the preferred 〇1 is 0; η is 〇; γ represents a fluoro group, a gas group or a bromo group. Or secondary phenyl; R3 or R3 R4 represents a transbasic group; and R1 represents hydrogen or fluorine. In the above chemical formula (1), particularly preferred m is 〇; η is 〇; γ represents a fluoro group at the 4- 1 〇 position, and is gas at the 4-position. Substituted, phenyl substituted at the 2- and 4-positions with a fluoro group or substituted with a gas group at the 2- and 4-positions; R3 or 'r3 and r4 represent a hydroxy group; and r1 represents hydrogen or fluoro. Further, 'in the above chemical formula (1), it is also preferred that η is 〇, m is 〇 or 1, Y represents a C6_C10-aryl group, and preferably a phenyl group, a benzyl group, a phenethyl group, a 15 propyl group, Butyl or phenylhexyl, which is optionally substituted one or more times by: ❹ aXVCV alkyl, c3_C8_ ring, C6_Ci "aryl, C6_Ci〇_aryl-Q-CV alkyl, CrC6 Alkoxy, C6_Ci〇_aryloxy, C6_Ci〇aryl-cvc8-bromo, thiol, c〇2H, Ci_C6_homoyloxy, C6_Ci〇20 aryloxycarbonyl, C6-Ci〇 -aryl-cvcv alkoxycarbonyl, CrC6-alkylcarbonyl, c6-c1 (rarylcarbonyl, C6_Ci〇_aryl_Ci_C8_alkylcarbonyl, CiC6_alkylcarboxy, c6-c1 (rarylcarboxyl) , Crc6_alkyl thiol, c6_Ci (r aryl thiol, Ci -C6-alkylmercaptocarbonyl, c3-c8-cycloalkylcarbonylcarbonyl, cvcv arylfluorenylcarbonyl, CrC6-alkylindenylcarboxy, c6_Ci〇_ 27 200932732 aryldecylcarboxy, CrCV alkylsulfonyl, CVCio-arylsulfonyl,

Ci_C6-炫基氧硫基、C6_Ci〇-芳基氧硫基，其中各者選擇性地被下列各者取代一或多次：cvcv 烷基、CVC6-烷氧基、COOH、選擇性地被Ci-C6-烷基取 5 代一或二次之conh2、so3h、胺基、硫氫基、羥基、硝基、氰基、氟代基、氣代基、溴代基、碘代基、CF3或OCF3 ; 其中該等選擇性取代基中之數者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統；或 b) —種飽和、不飽和或芳族雜環，其選擇性地被下列 _ 10 各者取代一或多次：Crc6-烷基、CrCV烷氧基、COOH、選擇性地被CrQ-烷基取代一或二次之CONh2、S03H、胺基、硫氫基、羥基、硝基、氰基、氟代基、氣代基、溴代基、碘代基、CF3或OCF3 ; c) S〇3H ;胺基；經選自下列群中的殘基取代一或多次 15 之胺基：Ci-CV院基、CVQ。-芳基、c6_c丨『芳基_Ci-c8_烧基、Ci_C6-nonyloxythio, C6_Ci〇-aryloxythio, each of which is optionally substituted one or more times by: cvcv alkyl, CVC6-alkoxy, COOH, optionally Ci -C6-alkyl is taken from the fifth or second conh2, so3h, amine, sulfhydryl, hydroxy, nitro, cyano, fluoro, carbyl, bromo, iodo, CF3 or OCF3; wherein the number of the selective substituents may be combined to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; or b) a saturated, unsaturated or aromatic heterocyclic ring, Optionally substituted by one or more of the following: Crc6-alkyl, CrCV alkoxy, COOH, optionally substituted by CrQ-alkyl one or two times CONh2, S03H, amine, sulfur a base, a hydroxyl group, a nitro group, a cyano group, a fluoro group, a carbyl group, a bromo group, an iodo group, a CF3 or an OCF3; c) S〇3H; an amine group; substituted with a residue selected from the group consisting of Or a number of 15 amino groups: Ci-CV hospital base, CVQ. -aryl, c6_c丨"aryl_Ci-c8_alkyl,

Ci-Q-烷基羰基、c：6-C1{r芳基羰基、Ci_C6_烷基磺醯基及 C6-C1()-芳基續醯基；c〇NH2 ; so2nh2 ; conh2或so2nh2， Ο f中該胺基官能度被選^_C6·燒基、c6_Ci〇芳基或C6_Ci〇_ 芳基CVC4-烧基的殘基取代一次或多次；硫氫基；經基；硝基，氰基；氣續醢基；選自氟代基、氣代基、漠代基或峨代基之_素；cf3 ; OCF3。在上述的化學式(1)中，亦較佳者係ηΛ0，而。亦較佳者係R1至R5彼此獨立地代表氫；經基；Ci C4_ 烷基；c6-cv芳基；Cl-C4-烧氧基；C6_Ci〇_芳氧基、c6_Ci〇_ 28 200932732 5 ❹ 10 15 ❹ 20 方基-CVc4-烷氧基；COOH ; cvc6-烷基羧基；C6-C1(r芳基羧基；CVCV烷基氫硫基；c6-c10-芳基氫硫基；crc6-烷基尹'酿基’ c6-c10-芳基績醯基；crC6-烧基氧硫基；C6-C10-芳基氣硫基；so3H ;胺基；經選自Crc6_烷基、c6_c10_芳基、C6-C1(r芳基-CrCr烷基、CrC6-烷基羰基、C6-C1()-芳基 &基Ci-C6-烧基崎酿基及C6-Ci〇-芳基績酿基的殘基取代一或多次之胺基；硫氫基；羥基；硝基；氰基；氟磺醯基；選自氟代基、氯代基、溴代基或碘代基之鹵素；CF3; OCF3 ; 或一種飽和、不飽和或芳族雜環，其選擇性地被下列各者取代一或多次：CVQ-烧基、crc6-燒氧基、COOH、S03H、胺基、硫氫基、羥基、硝基、氰基、氟代基、氯代基、溴代基、碘代基、cf3或ocf3。 R1至R5更佳係選自羥基、甲基、特_丁基、苯基、甲氧基、乙氧基、苯氧基、胺基、硫氫基、羥基、氰基、氟代基、氣代基、漠代基、硝基、CF3、OCF3、°比咬、CONH2、 S02NH2、四β坐或三β坐 R1至R5中之任一者亦較佳為苯基，其進一步被羥基、 CVCV烷氧基' COOH、S03H、胺基、硫氫基、羥基、硝基、氰基、氟代基 '氣代基、溴代基、碘代基、CF34〇CF3取代一或多次。在化學式(I)中，亦較佳者係γ代表苯基或苄基，其在鄰 -、間-及/或對-位置被下列各者取代：C! _C6_烷氧基、C6_C i〇_ 芳氧基、羥基、硝基、胺基、CONH2、s〇2NH2、氟代基、氣代基或OCF3。甚至更佳者，γ代表在鄰_、間_及/或對-位 29 200932732 置被取代一次、二次或三次之苯基、而取代基係獨立地選自曱氧基、乙氧基、特-丁氧基、苯氧基、羥基、硝基、 CONH2、S02NH2、氟代基、氯代基或〇CF3。在化學式(I)中，亦較佳者係當η為0及m為0或1時，R1 5 至R5係選自甲基、特-丁基、苯基、甲氧基、乙氧基、苯氧基、胺基、硫氩基、羥基、氰基、氟代基、氣代基、溴代基、石肖基、CF3、OCF3、n比口定、CONH2、SO2NH2、四0坐、三°坐或苯基，其進一步被下列各者取代一或多次：crc6-烷氧基、COOH、S03H、胺基、硫氫基、羥基、硝基、氰 ©Ci-Q-alkylcarbonyl, c: 6-C1{r arylcarbonyl, Ci_C6-alkylsulfonyl and C6-C1()-aryl fluorenyl; c〇NH2; so2nh2; conh2 or so2nh2, Ο The amino functionality in f is substituted one or more times with a residue selected from the group consisting of a C6-Ci-aryl group or a C6_Ci〇_aryl CVC4-alkyl group; a sulfhydryl group; a thiol group; a nitro group;气醢 ; ;; selected from fluoro, a gas base, a desert base or a halogen group; cf3; OCF3. In the above chemical formula (1), it is also preferred that η Λ 0, and. Also preferably, R1 to R5 independently of each other represent hydrogen; a trans group; Ci C4_alkyl; c6-cv aryl; Cl-C4-alkoxy; C6_Ci〇_aryloxy, c6_Ci〇_ 28 200932732 5 ❹ 10 15 ❹ 20 aryl-CVc4-alkoxy; COOH; cvc6-alkylcarboxy; C6-C1 (r arylcarboxy; CVCV alkyl thiol; c6-c10-aryl thiol; crc6-alkane基尹 '牛牛' c6-c10-aryl fluorenyl; crC6-alkyloxythio; C6-C10-arylsulfuryl; so3H; amine; selected from Crc6_alkyl, c6_c10_芳Base, C6-C1 (r-aryl-CrCr alkyl, CrC6-alkylcarbonyl, C6-C1()-aryl &-based Ci-C6-alkyl ketone and C6-Ci〇-aryl Substituting a residue for one or more amine groups; sulfhydryl; hydroxy; nitro; cyano; fluorosulfonyl; halogen selected from fluoro, chloro, bromo or iodo; CF3; OCF3; or a saturated, unsaturated or aromatic heterocyclic ring which is optionally substituted one or more times by: CVQ-alkyl, crc6-alkoxy, COOH, S03H, amine, sulfhydryl Base, hydroxyl, nitro, cyano, fluoro, chloro, bromo, iodo, cf3 or ocf3. R1 to R5 are preferred Selected from the group consisting of hydroxyl, methyl, tert-butyl, phenyl, methoxy, ethoxy, phenoxy, amine, sulfhydryl, hydroxy, cyano, fluoro, carbyl, molybdenyl , nitro, CF3, OCF3, ° ratio bite, CONH2, S02NH2, tetra-β-seat or tri-β sitting R1 to R5 are also preferably phenyl, which is further hydroxy, CVCV alkoxy 'COOH, S03H, an amine group, a sulfhydryl group, a hydroxyl group, a nitro group, a cyano group, a fluoro group 'a gas group, a bromo group, an iodo group, and a CF34〇CF3 are substituted one or more times. In the chemical formula (I), Preferably, γ represents a phenyl or benzyl group which is substituted at the ortho-, meta- and/or para-position by the following: C! _C6_alkoxy, C6_C i〇_ aryloxy, hydroxy, nitro Base, amine group, CONH2, s〇2NH2, fluoro group, gas group or OCF 3. Even better, γ represents substitution once, twice or in the adjacent _, inter _ and / or y - 29 200932732 a phenyl group of three times, and the substituents are independently selected from the group consisting of decyloxy, ethoxy, tert-butoxy, phenoxy, hydroxy, nitro, CONH2, S02NH2, fluoro, chloro or hydrazine CF3 In the chemical formula (I), it is also preferred When η is 0 and m is 0 or 1, R1 5 to R5 are selected from the group consisting of methyl, tert-butyl, phenyl, methoxy, ethoxy, phenoxy, amine, thio-aryl, Hydroxy, cyano, fluoro, carbyl, bromo, succinyl, CF3, OCF3, n, succinyl, CONH2, SO2NH2, tetras, tris, or phenyl, which are further replaced by One or more times: crc6-alkoxy, COOH, S03H, amine, sulfhydryl, hydroxy, nitro, cyanide

10 基、氟代基、氣代基、溴代基、碘代基、cf3或OCF3 ;及Y 代表苯基，其在鄰-及/或對-位置被下列各者取代：Crc6- ' 烷氧基、c6-c1(r芳氧基、羥基、硝基、CONH2、S02NH2、 - 氟代基、氯代基或OCF3。在一任擇的實施例中，本發明係有關於具化學式(I)的 15 一化合物：10, fluoro, carbyl, bromo, iodo, cf3 or OCF3; and Y represents a phenyl group which is substituted at the ortho- and/or p-position by: Crc6- 'alkoxy a group, c6-c1 (r aryloxy, hydroxy, nitro, CONH2, S02NH2, -fluoro, chloro or OCF3. In an optional embodiment, the invention relates to formula (I) 15 a compound:

(I) 其中 R1至R5係彼此獨立地代表： 20 氫； CVCV院基、c3-c8-環炫基、C6-C1(r芳基、c6-c10-芳基-CrCV烧基、CVCV炫氧基、C6-C]。-芳氧基、C6-C10-芳 30 200932732 基-CrC8-烷氧基、CrCV烷氧基羰基、c6-c1()-芳氧基羰基、C6-C1()-芳基-CVCV烷氧基羰基、CVCV烷基羰基、 c6-c1()-芳基羰基、C6-C1()-芳基-CVCV烷基羰基、CVCV烷基羧基、C6-C10-芳基羧基、CVCV烷基氫硫基、C6-C10-芳 5 基氫硫基、crc6-烷基巯基羰基、c3-c8-環烷基巯基羰基、C6-C1()-芳基Μ基羰基、CrC6-烷基酼基羧基、C6-C10-芳基巯基羧基、Q-cv烷基磺醯基、c6-c1()-芳基磺醯基、 crc6-烷基氧硫基、c6-c1(r芳基氧硫基，其中各者選擇性地〇被下列各者取代一次或多次： 10 CrCV烷基；crc6-烷氧基；c6-c10-芳氧基； co2h ; so3h ; C〇NH2 ; S02NH2 ; CONH2 或 S02NH2，其中該胺基官能度被選自CkCV烷基、c6-c1()-芳基或 C6-C10-芳基-CVC4-烷基的殘基取代一次或多次，及其中在一種經二-Q-C6-烷基取代的胺基官能度之情況下，該 15 烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：CVC6-烷基、c6-c10-芳 ® 基、C6-C1(r芳基-CVC4-烷基、crc6-烷基羰基、c6-c10- 芳基羰基、crc6-烷基磺醯基及c6-c1()-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基； 20 峨代基，CF3或OCF3， co2h ; so3h ; 胺基；(I) wherein R1 to R5 are independently of each other: 20 hydrogen; CVCV, c3-c8-cyclo, C6-C1 (raryl, c6-c10-aryl-CrCV, CVCV) , C6-C]-aryloxy, C6-C10-aryl 30 200932732 base-CrC8-alkoxy, CrCV alkoxycarbonyl, c6-c1()-aryloxycarbonyl, C6-C1()- Aryl-CVCV alkoxycarbonyl, CVCV alkylcarbonyl, c6-c1()-arylcarbonyl, C6-C1()-aryl-CVCV alkylcarbonyl, CVCV alkylcarboxy, C6-C10-arylcarboxy , CVCV alkyl thiol, C6-C10-aryl 5 thiol, crc6-alkyl fluorenylcarbonyl, c3-c8-cycloalkylcarbonylcarbonyl, C6-C1()-aryldecylcarbonyl, CrC6- Alkyl fluorenylcarboxy, C6-C10-aryldecylcarboxy, Q-cv alkylsulfonyl, c6-c1()-arylsulfonyl, crc6-alkyloxythio, c6-c1 (r-aryl a oxythio group, each of which is optionally substituted one or more times by: 10 CrCV alkyl; crc6-alkoxy; c6-c10-aryloxy; co2h; so3h; C〇NH2; S02NH2 CONH2 or S02NH2, wherein the amino functionality is substituted one or more times by a residue selected from the group consisting of CkCV alkyl, c6-c1()-aryl or C6-C10-aryl-CVC4-alkyl And wherein in the case of a di-Q-C6-alkyl substituted amine functionality, the 15 alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; a residue selected from the group consisting of Substituting one or more amine groups: CVC6-alkyl, c6-c10-aryl®, C6-C1 (raryl-CVC4-alkyl, crc6-alkylcarbonyl, c6-c10-arylcarbonyl, Crc6-alkylsulfonyl and c6-c1()-arylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; ketone; bromo; 20 oxime, CF3 Or OCF3, co2h; so3h; amine group;

經選自下列群中的殘基取代一或多次之胺基：CVCV 31 200932732 烧基、C6-Ci〇-芳基、C6-Ci〇-方基-Ci_C6-烧基、C!-C6-烧基羰基、c6-c10-芳基羰基、crc6-烷基磺醯基及C6-C1(}-芳基磺醯基；具下列化學式（II)之一種經二取代的胺基：Substituting one or more amine groups with a residue selected from the group consisting of CVCV 31 200932732 alkyl, C6-Ci〇-aryl, C6-Ci〇-square-Ci_C6-alkyl, C!-C6- An alkyl group, a c6-c10-arylcarbonyl group, a crc6-alkylsulfonyl group, and a C6-C1(}-arylsulfonyl group; a disubstituted amino group of the following formula (II):

—N W H7] 5 ° (II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選—N W H7] 5 ° (II) where 〇 represents 0 or 1, and W represents oxygen, CH2 or NR6, R6 is selected

自氫與CrC6-烷基，及其中化學式(II)中的亞甲基可選擇性地被CrC6-烷基、氟代基或氯代基取代一或二次； conh2 ； 10 so2nh2 ; CONH2或S〇2NH2，其中該胺基官能度被選自crc6-烧基、C6-Ci〇-芳基或C6-Ci〇-方基-C1-C6-烧基的殘基取代一或二次，及其中在一種經二-crc6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環； 15 硫氫基；From hydrogen to CrC6-alkyl, and the methylene group of formula (II) thereof may be optionally substituted one or two times with CrC6-alkyl, fluoro or chloro; conh2; 10 so2nh2; CONH2 or S 〇2NH2, wherein the amino functionality is substituted one or two times with a residue selected from the group consisting of crc6-alkyl, C6-Ci〇-aryl or C6-Ci〇-aryl-C1-C6-alkyl, and In the case of a di-crc6-alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; 15 sulfhydryl;

羥基；頌基；氰基；氣石黃酿基， 20 選自氟代基、氣代基、溴代基或碘代基之鹵素； CF3 ; OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜 32 200932732 環式環系統，其選擇性地被下列各者取代一或多次： CVCV 烷基；CrC6-烷氧基；COOH ; so3h ; conh2 ; so2nh2 ; CONH2或S02NH2，其中該胺基官能度被選gCrCV烷基、C6-C1Q-芳基或C6-C1(r芳基-CVC4-5 烷基的殘基取代一次或多次，及其中在一種經二-CrC6-Hydroxy; fluorenyl; cyano; gas yellow wine, 20 halogen selected from fluoro, carbyl, bromo or iodo; CF3; OCF3; or a saturation consisting of up to 10 atoms, Unsaturated or aromatic heterocyclic 32 200932732 Ring-ring system, which is optionally substituted one or more times by: CVCV alkyl; CrC6-alkoxy; COOH; so3h; conh2; so2nh2; CONH2 or S02NH2, wherein The amine functionality is selected one or more times by substitution of a residue of gCrCV alkyl, C6-C1Q-aryl or C6-C1 (raryl-CVC4-5 alkyl, and one in two-CrC6-

烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、c6-c10-芳基、c6-c10-芳基 © -CkQ-烷基、CkQ-烷基羰基、CVQ。-芳基羰基、CVCV 10 烧基續酿基及C6-Ci〇-方基績酿基，硫氮基，楚基；石肖 ' 基；氰基；氟代基；氯代基；溴代基；碘代基；cf3或 OCF3 ; 及其中R1至R5中之任二或多者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統； 15 η代表0 ; m代表0 ; Y代表苯基，其選擇性地被下列各者取代一或多次： ® a)CrC6-烷基、C6-C10-芳基、C6-C1()-芳基-Q-CV 烷基、CVC6-烷氧基、C6-C1()-芳氧基、C6-C1()-芳基-CVC8-烷氧基、CrC6-烷氧基羰基、C6-C1()-芳氧基羰基、C6-C10-芳 20 基-CVCV烷氧基羰基、CVC6-烷基羰基、C6-C1Q-芳基羰基、c6-c1()-芳基-crc8-烷基羰基、crc6-烷基羧基、。6_。10_方基叛基、烧基風石荒基、C6_Ci〇-芳基氮硫基、CVCV烷基巯基羰基、c3-c8-環烷基巯基羰基、 c6-c1()-芳基巯基羰基、crc6-烷基酼基羧基、c6-c1()-芳基 33 200932732 酼基羧基、crc6-烷基磺醯基、c6-c1()-芳基磺醯基、 Ci_C6-烧基氧硫基、C6-Ci〇-芳基氣硫基，其中各者選擇性地被下列各者取代一或多次：crc6-烷基；crc6-烷氧基；選擇性地被crc6-烷基取代一或二 5 次之conh2或so2nh2 ; S03H ; C02H ;胺基；經選自下列群中的殘基取代一或多次之胺基：Ci-Cf烧基、C6-Ci〇-芳基、C6_Ci〇-芳基-C1-C4-烧基、C1-C6-烧基叛基、C6-Ci〇-芳基幾基、C1-C6-烧基績酿基及C6-C10-芳基石黃酿基，硫氮基；經基；硝基；氮基；氣代基；氯代基；臭代基；議 10 代基；CF3或OCF3 ; 其中該等選擇性取代基中之數者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統；或 b)—種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次〔Ci-CV 15 烷基；CVCV烷氧基；COOH ;選擇性地被Ci-CV烷基取代一或二次之conh2或so2nh2 ; so3h ;胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、c6-c10-芳基、C6-C1()-芳基-CrQ-烷基、CrC6-烷基羰基、C6-C1()-芳基羰基、crc6-烷基磺醯基及C6-C1Q-芳基磺醯基；硫氫基；羥 20 基；硝基；氰基；氟代基；氣代基；溴代基；碘代基； CF3 或 OCF3 ;或 C)經基；硫氫基；梢基；氰基；氟代基；氣代基；漠代基；碘代基；cf3 ; ocf3 ; co2h ; S03H ; CONH2 ; so2nh2 ; CONH2或S〇2NH2，其中該胺基官能度被選自 200932732 G-Q-烧基、C6-C10-芳基或C6_q『芳基_Cl_c4-炫基的殘基取代一次或多次，及其中在一種經二_Ci_c6_烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基： 5 Ci_C6_炫基、C6-C10-芳基、c6_c10-芳基-CrC8-炫基、ci_c6-烧基羰基、CVCur芳基幾基、Ci_C6_烧基績酿基及C6-C10-芳基績醯基；具下列化學式(II)之一種經二取代的胺基：In the case of an alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of: crc6- Alkyl, c6-c10-aryl, c6-c10-aryl©-CkQ-alkyl, CkQ-alkylcarbonyl, CVQ. -arylcarbonyl, CVCV 10 calcined base and C6-Ci〇-square base, sulfuryl group, Chuji; Shixiao' base; cyano; fluoro group; chloro group; bromo group; Substituent; cf3 or OCF3; and any two or more of R1 to R5 thereof may be combined to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; 15 η represents 0; m represents 0; Y Represents a phenyl group which is optionally substituted one or more times by: a) CrC6-alkyl, C6-C10-aryl, C6-C1()-aryl-Q-CV alkyl, CVC6- Alkoxy, C6-C1()-aryloxy, C6-C1()-aryl-CVC8-alkoxy, CrC6-alkoxycarbonyl, C6-C1()-aryloxycarbonyl, C6-C10 -Aryl 20-CVCV alkoxycarbonyl, CVC6-alkylcarbonyl, C6-C1Q-arylcarbonyl, c6-c1()-aryl-crc8-alkylcarbonyl, crc6-alkylcarboxy,. 6_. 10_方基叛基,烧基风石荒基, C6_Ci〇-aryl sulfoximine, CVCV alkyl fluorenylcarbonyl, c3-c8-cycloalkylfluorenylcarbonyl, c6-c1()-aryldecylcarbonyl, crc6- Alkyl fluorenylcarboxy, c6-c1()-aryl 33 200932732 decylcarboxy, crc6-alkylsulfonyl, c6-c1()-arylsulfonyl, Ci_C6-alkyloxythio, C6- Ci〇-arylsulfoyl, each of which is optionally substituted one or more times by the following: crc6-alkyl; crc6-alkoxy; optionally substituted by crc6-alkyl one or two times Conh2 or so2nh2; S03H; C02H; amine group; amine group substituted one or more times with a residue selected from the group consisting of Ci-Cf alkyl, C6-Ci〇-aryl, C6_Ci〇-aryl- C1-C4-alkyl, C1-C6-alkyl group, C6-Ci〇-aryl group, C1-C6-alkyl base, and C6-C10-aryl stone base, sulfur nitrogen; a nitro group; a nitrogen group; a gas group; a chloro group; a odor group; a 10th generation group; CF3 or OCF3; wherein the plurality of the selective substituents can be combined to form a fused saturation, An unsaturated or aromatic homocyclic or heterocyclic ring system; or b) a species saturated with up to 10 atoms, An unsaturated or aromatic heterocyclic ring system which is optionally substituted one or more times by the following: [Ci-CV 15 alkyl; CVCV alkoxy; COOH; optionally substituted by Ci-CV alkyl Or a second conh2 or so2nh2; so3h; an amine group; one or more amino groups substituted with a residue selected from the group consisting of: crc6-alkyl, c6-c10-aryl, C6-C1()-aryl -CrQ-alkyl, CrC6-alkylcarbonyl, C6-C1()-arylcarbonyl, crc6-alkylsulfonyl and C6-C1Q-arylsulfonyl; sulfhydryl; hydroxy 20; Cyano; fluoro; thiol; bromo; iodo; CF3 or OCF3; or C) thiol; thiol; Substituent; iodo group; cf3; ocf3; co2h; S03H; CONH2; so2nh2; CONH2 or S〇2NH2, wherein the amine functionality is selected from 200932732 GQ-alkyl, C6-C10-aryl or C6_q Substituting one or more residues of the base_Cl_c4-thingyl group, and in the case of an amine functionality substituted with a di-Ci_c6-alkyl group, the alkyl residue may be combined to form a 5 or 6 membered ring Amine; one or more substituted with a residue selected from the group consisting of Amine group: 5 Ci_C6_Hyun group, C6-C10-aryl group, c6_c10-aryl-CrC8-Hyun group, ci_c6-alkyl group, CVCur aryl group, Ci_C6_alkyl base and C6-C10 - an aryl group; a disubstituted amine group of the following formula (II):

其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自 10 氫與Ci-C4-烧基’及其中化學式(II)中的亞甲基可選擇性地被CrCp烷基、氟代基或氯代基取代一或二次；前提在於： a) R2或R4並非代表取代基c(=A)_N(B)_s〇2_NR6R7,其中 A代表氧或硫’ B代表氫、氰基、CrC6_烷基、CrCV烷氧基 15 -烷基、C3_C7-環烷基、Cs-CV烯烴基、c3-C6-炔基或選擇性地被取代的苄基衍生物，及R6與R7係彼此獨立地代表氫或一個有機殘基或一起代表一個有機環狀結構； b) 當Y代表未經取代的苯基時，尺!至尺5彼此獨立地並非代表氫、氟代基、溴代基、氣代基、碘代基或一烷基游離基； 20 C)R2或r4並非代表一種吡唑-3-基-衍生物；及 d)經R1至R5取代的苯基環及γ並非代表下列組合： 35 200932732 經R1至R5取代的苯基環 Y 2-氯苯基 4-氣苯基 2,3-二曱基苯基 4-氣苯基 2,4-二氣苯基 4-氣苯基 2-氣-3-甲基苯基 4-氣苯基 2,5-二氟苯基 4-曱基苯基 2-曱氧基-4-氣笨基 4-氣苯基 2-氣苯基 4-甲基苯基 2,6-二氣苯基 4-氣苯基 2-(三氟甲基氫硫基)苯基苯基 2,3,4-三曱基苯基 4-氣苯基 2,5-二氟苯基 4-溴苯基 2,4-二甲基苯基 4-氣苯基 4-氣苯基 4-氣苯基 3-氣苯基 4-氣苯基 4-溴苯基 4-氣苯基 2-氣苯基 4-溴苯基 2,5-二氟苯基 4-氣苯基 4-氣苯基 4->臭苯基 3,5-二曱基苯基 4-氣苯基 4-三氟甲氧基苯基 4-辛基苯基 4-三氟甲氧基苯基 3-苯氧基苯基 2,3-二氫-2,2-二曱基-7-苯並呋喃基苯基在上述的化學式(I)中，R1至R5較佳彼此獨立地代表：氫；羥基；Wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from 10 hydrogen and Ci-C 4 -alkyl and the methylene group in the formula (II) is optionally CrCp alkyl, The fluoro or chloro group is substituted one or two times; the premise is: a) R2 or R4 does not represent a substituent c(=A)_N(B)_s〇2_NR6R7, where A represents oxygen or sulfur 'B stands for hydrogen, cyanide Base, CrC6-alkyl, CrCV alkoxy 15-alkyl, C3_C7-cycloalkyl, Cs-CV alkene, c3-C6-alkynyl or a selectively substituted benzyl derivative, and R6 and R7 Respectively, independently of each other, represent hydrogen or an organic residue or together represent an organic cyclic structure; b) when Y represents an unsubstituted phenyl group, the ruler! to ruler 5 independently of each other does not represent hydrogen, fluoro, bromo a substituent, a carbyl group, an iodo group or a monoalkyl radical; 20 C) R 2 or r 4 does not represent a pyrazol-3-yl-derivative; and d) a phenyl ring substituted with R 1 to R 5 and γ Does not represent the following combination: 35 200932732 Phenyl ring Y 2-chlorophenyl 4-phenylphenyl 2,3-dimercaptophenyl 4-phenylphenyl 2,4-diphenylphenyl 4 substituted by R1 to R5 -Phenyl 2-methane-3-methylphenyl 4-phenylene 2, 5-difluorophenyl 4-mercaptophenyl 2-methoxy-4-pyrimyl 4-phenylphenyl 2-phenylphenyl 4-methylphenyl 2,6-diphenylphenyl 4-gas Phenyl 2-(trifluoromethylhydrothio)phenylphenyl 2,3,4-trimethylphenyl 4-pyrophenyl 2,5-difluorophenyl 4-bromophenyl 2,4- Dimethylphenyl 4-phenylphenyl 4-phenylphenyl 4-phenylphenyl 3-phenylphenyl 4-phenylphenyl 4-bromophenyl 4-phenylphenyl 2-phenylphenyl 4-bromophenyl 2,5-difluorophenyl 4-phenylphenyl 4-phenylphenyl 4->odor phenyl 3,5-dimercaptophenyl 4-phenylphenyl 4-trifluoromethoxyphenyl 4- Octylphenyl 4-trifluoromethoxyphenyl 3-phenoxyphenyl 2,3-dihydro-2,2-dimercapto-7-benzofuranylphenyl group in the above formula (I) Wherein R1 to R5 are preferably independently of each other: hydrogen; hydroxyl;

Ci-C。-烧基、C6_Ci〇-芳基、Ci_C6_ 烧氧基、C6-Ci〇-芳 5 氧基、C6-C10-芳基-CVCV烷氧基、CVCV烷基羧基、 c6-c1()-芳基羧基、crc6-烷基磺醯基、c6-c1()-芳基磺醯基，其中各者選擇性地被下列各者取代一次或多次：CVC6-烷基、Crc6-烷氧基、胺基、CrCV烷基胺基、二-CVC6- 36 200932732 烷基胺基、羥基、氟代基、氯代基、溴代基、氰基、cf3 或 ocf3 ; 胺基；經選自Q-C6-烷基、C6-C1Q-芳基的殘基取代一或多次之 5 胺基； 1-吡咯基、2-吡咯基或3-吡咯基，其選擇性地被一或多個選自CrC6-烷基、胺基、氟代基、氯代基或CF3之殘基取代；具下列化學式(II)之一種經二取代的胺基：Ci-C. -alkyl, C6_Ci〇-aryl, Ci_C6_alkoxy, C6-Ci〇-aryl 5 oxy, C6-C10-aryl-CVCV alkoxy, CVCV alkylcarboxy, c6-c1()-aryl Carboxyl, crc6-alkylsulfonyl, c6-c1()-arylsulfonyl, each of which is optionally substituted one or more times by: CVC6-alkyl, Crc6-alkoxy, amine Base, CrCV alkylamino, di-CVC6- 36 200932732 alkylamino, hydroxy, fluoro, chloro, bromo, cyano, cf3 or ocf3; amine; selected from Q-C6- a residue of an alkyl group, a C6-C1Q-aryl group substituted with one or more amino groups; a 1-pyrrolyl group, a 2-pyrrolyl group or a 3-pyrrolyl group, which is optionally selected from one or more selected from the group consisting of CrC6- Substituted by a residue of an alkyl group, an amine group, a fluoro group, a chloro group or a CF3; a disubstituted amino group having the following formula (II):

L Jo (II) 10 其中Ο代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-C6-烷基，及其中化學式(II)中的亞甲基可選擇性地被Cl-C6-烧基、氟代基或氣代基取代一或二次； conh2 ; so2NH2; 15 conh2或S02NH2，其中該胺基官能度被選自crc6-烷基或c6-c1()-芳基的殘基取代一或二次；氟代基；氣代基；溴代基； 20 CF3 ;或 OCF3。在上述的化學式⑴中，更佳R1至R5中之一或多者代表氫、氟或氣。最佳R1或R5代表氫或氟。 37 200932732 在上述的化學式(I)中，更佳R1至R5中之一或多者代表羥基；或代表Q-CV烧氧基、C6-C1G-芳氧基、c6_Ci〇_芳基 -CrC6-烧氧基、crc6-烧基竣基、c6-c10-芳基叛基、 Ci-CV烧基靖酿基、CVCiq-芳基續醯基，其中各者選擇性地 5 被下列各者取代一次或多次：CrC6-院基、crC6-烷氧基、胺基、CrC6-烷基胺基、二-CVC6·烷基胺基、選擇性地被Ci-CV院基或CVCio-芳基取代一或二次之c〇NH2或 S02NH2、羥基、氟代基、氣代基、溴代基、氰基、cf3或 OCF3。 ίο 更佳R2，r3或r4中之一者代表羥基；或代表q-cv烷氧基、C6-Ci〇-芳氧基或C6-C10-芳基-Ci-CV院氧基，其中各者選擇性地被下列各者取代一或多次：CVC6-烷基、crc6-烷氧基、胺基、G-C6-烷基胺基、二-CrCe-烷基胺基、選擇性地被Ci-CV烷基或C6-C1(r芳基取代一或二次之c〇NH2或 15 so2nh2、羥基、氟代基、氯代基或溴代基。在上述的化學式(I)中，更佳R1至R5中之一或多者代表胺基，經選自Ci-C6-烧基、CVCio-芳基的殘基取代一或多次之胺基；或具下列化學式(II)之一種經二取代的胺基：L Jo (II) 10 wherein Ο represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and Q-C 6 -alkyl, and the methylene group in the formula (II) is optionally Substituting one or two times with a Cl-C6-alkyl group, a fluoro group or a gas group; conh2; so2NH2; 15 conh2 or S02NH2, wherein the amine functionality is selected from the group consisting of crc6-alkyl or c6-c1()- The residue of the aryl group is substituted one or two times; a fluoro group; a gas group; a bromo group; 20 CF3; or OCF3. In the above chemical formula (1), more preferably one or more of R1 to R5 represents hydrogen, fluorine or gas. Most preferably R1 or R5 represents hydrogen or fluorine. 37 200932732 In the above formula (I), more preferably one or more of R1 to R5 represents a hydroxyl group; or represents a Q-CV alkoxy group, a C6-C1G-aryloxy group, a c6_Ci〇_aryl-CrC6- Alkoxy, crc6-alkyl sulfhydryl, c6-c10-aryl thiol, Ci-CV aryl thiol, CVCiq-aryl thiol, each of which is optionally substituted 5 by one of the following or Multiple times: CrC6-homogeneous, crC6-alkoxy, amine, CrC6-alkylamino, di-CVC6.alkylamino, optionally substituted by Ci-CV or CVCio-aryl Secondary c〇NH2 or S02NH2, hydroxy, fluoro, carbyl, bromo, cyano, cf3 or OCF3. Preferably, one of R2, r3 or r4 represents a hydroxyl group; or represents a q-cv alkoxy group, a C6-Ci〇-aryloxy group or a C6-C10-aryl-Ci-CV alkoxy group, each of which Optionally substituted by one or more of the following: CVC6-alkyl, crc6-alkoxy, amine, G-C6-alkylamino, di-CrCe-alkylamino, optionally Ci -CV alkyl or C6-C1 (raryl substituted for one or two times c〇NH2 or 15 so2nh2, hydroxy, fluoro, chloro or bromo. In the above formula (I), preferably One or more of R1 to R5 represents an amine group, one or more amine groups substituted with a residue selected from a Ci-C6-alkyl group, a CVCio-aryl group; or one of the following chemical formula (II) Substituted amine group:

—N W ° (II) 20 其中〇代表〇或1，而W代表氧、CH2或NR6，R6係選自氫與Q-C4-烷基，及其中化學式(II)中的亞甲基可選擇性地被CrCr烷基、氟代基或氣代基取代一或二次。更佳R2、R3或R4中之一者代表胺基；被選自Ci-CV烷 200932732 基、c6-c1Q-芳基的殘基取代一或二次之胺基；或具下列化學式(II)之一種經二取代的胺基： Γ~\—NW ° (II) 20 wherein 〇 represents 〇 or 1, and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and Q-C 4 alkyl, and the methylene selectivity in the chemical formula (II) The ground is replaced by a CrCr alkyl group, a fluoro group or a gas group for one or two times. More preferably, one of R 2 , R 3 or R 4 represents an amine group; an amine group substituted one or two times with a residue selected from the group consisting of Ci-CV alkane 200932732, a c6-c1Q-aryl group; or the following formula (II) A disubstituted amine group: Γ~\

—N W Η7] ° (II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自 5 氫與CVCr烷基，及其中化學式(II)中的亞甲基可選擇性地被CrC4-烷基、氟代基或氯代基取代一或二次。在上述的化學式(I)中，更佳Y代表苯基，其被下列各者〇取代一或多次： a)Ci-CV 烧基、C6-Ci〇-芳基、C6-Ci〇-芳基-Ci_C6_ 烧 10 基、Ci_C6-烧氧基、C6-Ci〇-^氧基、C6-Ci〇-芳基-Ci-Cg-烧氧基，其中各者選擇性地被下列各者取代一次或多次： CrQ-烷基；CrC6-烷氧基；S03H ; C02H ;胺基；經選自下列群中的殘基取代一或多次之胺基：Q-CV烷基、 c6-c1(r芳基、C6-C1(r芳基-CVC6-烷基、Q-CV烷基羰基、 15 C6-C1()-芳基羰基、CVCV烷基磺醯基及c6-c1()-芳基磺醯 ® 基；硫氫基；羥基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；CF3 ; CONH2 ; S02NH2 ; OCF3 ;或其中該胺基官能度被CrCV烷基取代一次或二次之CONH2或 so2nh2 ; 20 或被： b)羥基；硫氫基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；cf3 ; ocf3 ; co2h ; S03H ; CONH2 ; S〇2NH2 ;或CONH2或S02NH2，其中該胺基官能度被 39 200932732—NW Η7] ° (II) wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from 5 hydrogen and CVCr alkyl, and the methylene group in the formula (II) is optionally Substituted one or two times by CrC4-alkyl, fluoro or chloro. In the above formula (I), more preferably Y represents a phenyl group which is substituted one or more times by the following: a) Ci-CV alkyl group, C6-Ci〇-aryl group, C6-Ci〇-aryl group a group of -Ci_C6_, 10 alkyl, Ci_C6-alkoxy, C6-Ci〇-oxy, C6-Ci〇-aryl-Ci-Cg-alkoxy, each of which is optionally substituted once by Or multiple times: CrQ-alkyl; CrC6-alkoxy; S03H; C02H; amine; amine substituted one or more times with a residue selected from the group consisting of Q-CV alkyl, c6-c1 ( Raryl, C6-C1 (raryl-CVC6-alkyl, Q-CV alkylcarbonyl, 15 C6-C1()-arylcarbonyl, CVCV alkylsulfonyl and c6-c1()-aryl Sulfo] group; sulfhydryl; hydroxy; nitro; cyano; fluoro; chloro; bromo; iodo; CF3; CONH2; S02NH2; OCF3; or wherein the amine functionality is CrCV The alkyl group is substituted once or twice with CONH2 or so2nh2; 20 or by: b) hydroxy; sulfhydryl; nitro; cyano; fluoro; thio; bromo; iodo; cf3; ocf3; Co2h ; S03H ; CONH2 ; S〇2NH2 ; or CONH2 or S02NH2, wherein the amine functionality is 39 200932732

CrC6-烧基、C6-C10-芳基、C6-Ci〇-芳基-CrC6-烧基取代一次或二次，其中在一種經二-Ci-CV烧基取代的胺基官能度之情況下，該烧基殘基可結合而形成5或6員環；胺基；被 Q-CV烷基或苯基取代一或多次之胺基；具下列化學式(Π) 5 之一種經二取代的胺基： —l·/ w ^ ° (II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與CVCV烷基，及其中化學式(Π)中的亞曱基可選擇性地 €1 被CrC6-烷基、氟代基或氣代基取代一或二次； 10 或被： ‘ c)一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次：Q-CV 烷基；Q-C6-烷氧基；COOH ; CONH2 ; S02NH2 ;其中該胺基官能度被c!-c6-烷基取代一次或二次之c〇NH2或 15 S02NH2，其中該CrCV烷基可結合而形成5或6員環； sc^h ;胺基；經選自下列群中的殘基取代一或多次之胺 Ο 基：CVCV院基、c6-c1(r芳基、C6-C1(r芳基-CrCV炫基、CrC6-alkyl, C6-C10-aryl, C6-Ci〇-aryl-CrC6-alkyl substituted one or two times, in the case of an amine functionality substituted with a di-Ci-CV alkyl group The alkyl group may be bonded to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times by a Q-CV alkyl group or a phenyl group; and a disubstituted group having the following chemical formula (Π) 5 Amine group: —l·/ w ^ ° (II) wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and CVCV alkyl, and the fluorenyl group in the formula (Π) Alternatively, 1 1 may be substituted by a CrC6-alkyl, fluoro or ke group for one or two times; 10 or by: 'c) a saturated, unsaturated or aromatic heterocyclic ring consisting of up to 10 atoms a ring system which is optionally substituted one or more times by: Q-CV alkyl; Q-C6-alkoxy; COOH; CONH2; S02NH2; wherein the amine functionality is c!-c6-alkane Substituting one or two times of c〇NH2 or 15 S02NH2, wherein the CrCV alkyl group may be combined to form a 5 or 6 membered ring; sc^h; an amine group; one or more times substituted with a residue selected from the group consisting of Amine oxime: CVCV hospital base, c6-c1 (r aryl, C6 -C1(r-aryl-CrCV ray group,

Ci-CV烷基羰基、c6-c1(r芳基羰基、Cj-CV烷基磺醯基及 CVC1()-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代 20 基；氣代基；溴代基；碘代基；CF3 ;或〇CF3。甚至更佳者係γ代表苯基’其被下列各者取代一或多次：CVCV院基；笨基；CrC6_^氧基；羥基；氟代基；氣代基，溴代基；CF3 ; 〇CF3 ;胺基；或選擇性地被crC6- 40 200932732 烷基取代一或二次之CONH2或SC^NH2 ’其中該等選擇性的 CrC6-烷基殘基可結合而形成5或6員環。又更佳者係m代表0，及Y代表被羥基、氟代基、氣代基或溴代基取代一或二次之苯基。 5 ❹ 10 15 ❹ 20 最佳者係m代表〇 ;及Y代表苯基，其在4_位置被氟代基取代、在4-位置被氣代基取代、在2-與4-位置被氟代基取代、在2-與4-位置被氯代基取代或在4-位置被苯基取代。在上述的化學式⑴中，特佳m為0 ; η為0 ; Y代表被氟代基、氯代基或溴代基取代一或二次之苯基；及R2至R4中之任一者代表OR7，其中R7係選自氫與Ci_C4_烷基。在上述的化學式⑴中，亦非常佳者Ci-CV alkylcarbonyl, c6-c1 (r arylcarbonyl, Cj-CV alkylsulfonyl and CVC1()-arylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro 20 Base; gas group; bromo group; iodo group; CF3; or 〇CF3. Even better, γ represents phenyl' which is replaced by one or more of the following: CVCV hospital base; stupid base; CrC6_^ Oxyl; hydroxy; fluoro; thio, bromo; CF3; 〇CF3; amine; or optionally substituted by crC6- 40 200932732 alkyl one or two of CONH2 or SC^NH2 ' The isoselective CrC6-alkyl residue may be combined to form a 5 or 6 membered ring. More preferably, m represents 0, and Y represents one or two substituted with a hydroxy, fluoro, valyl or bromo group. Substituted phenyl. 5 ❹ 10 15 ❹ 20 The best is that m represents 〇; and Y represents phenyl, which is substituted at the 4 position by a fluoro group, at the 4-position by a gas group, at 2 The 4-position is substituted by a fluoro group, substituted by a chloro group at the 2- and 4-positions or substituted by a phenyl group at the 4-position. In the above chemical formula (1), particularly preferably m is 0; η is 0; Y represents Replace one or two with a fluoro, chloro or bromo group The phenyl group;. R2 to R4, and any one of the representative OR7, wherein R7 is selected from hydrogen and alkyl Ci_C4_ ⑴ above formula, the person is also very good

;11為0 ; Y 代表苯基，其在4-位置被氟代基取代、在4位置被氣代基取代、在2-與4·位置被氟代基取代或在2_與4位置被氣代基取代，及R至R4中之任一者代表〇R7，其中R7係選自氫與 C1-C4-统基。在上述的化學式(1)中，亦非常佳者係m為0 ; η為0 ; Y 代表被氟代基、氣代基或溴代基取代—或二次之苯基，及 R3或者R3與R4代表羥基。在上述的化學式⑴中，亦非常佳者係m為0 ; η為〇 ; γ 代表苯基，其在4·位置被氟代基取代、在4位置被氣代基取代、在2-與4-位置被氟代基取代或在2與4位置被氯代基取代，及R3或者R3與R4代表羥基。在上述的化學式①中，特佳; η為G ; Υ代表被氣代基、氣代基或漠代絲代-或二次之苯基；R2至R4中之任一 41 200932732 者代表〇R7，其中R7係選自氫與CrC4-烧基，·及Ri代表氟。在上述的化學式(I)中，特佳111為〇 ; n為〇 ; γ代表苯基，其在4-位置被氟代基取代、在4_位置被氣代基取代、在2_ 與\位置被氟代基取代或在2_與4_位置被氯代基取代；γ 5至&中之任一者代表〇R7,其中R7係選自氫與CrC4_烧基；及Rl代表氟。在上述的化學式⑴中，特佳〇1為〇 ; 〇為〇 ; 丫代表被氟代基、氣代基或溴代基取代—或二次之苯基；R3或者R3與 R4代表羥基；及R1代表氟。 ❹ 10 在上述的化學式⑴中，特佳m為〇; n為〇;γ代表苯基，八在4位置被氟代基取代、在4-位置被氯代基取代、在2_ 與4-位置被氟代基取代或在2-與4-位置被氣代基取代；R3 或者r3與R4代表羥基；及R1代表氟。而且’在化學式(I)中，亦較佳者係Ri至R5選自羥基、 15甲基、特-丁基、苯基、甲氧基、乙氧基、苯氧基、胺基、硫氫基、羥基、氰基、氟代基、氣代基、溴代基、硝基、 CF3、ocf3、吡啶、conh2、so2nh2、四唑或***。 © 亦較佳者，R1至R5中之至少一者係一種飽和、不飽和或芳族雜環，其選擇性地被下列各者取代一或多次：CrC6-2〇燒基、CrC6-烧氧基、C00H、S03H、胺基、硫氫基、羥基、硝基、氰基、氟代基、氣代基、溴代基、哄代基、CF3或〇cf3，或進一步被下列各者取代一或多次之苯基：Ci_C6_烷氧基、 C〇〇H、SOgH、胺基、硫氫基 '羥基、硝基、氰基、氟代基、氣代基、溴代基、碘代基、cf3或ocf3。 42 200932732 任擇地，Rl至R5中之至少-者亦較佳為CONH2 ; so2NH2，或CONH24S02NH2，其中該胺基官能度被選自11 is 0; Y represents a phenyl group which is substituted by a fluoro group at the 4-position, substituted with a gas group at the 4-position, substituted with a fluoro group at the 2- and 4-positions, or at the 2 and 4 positions. The gas group is substituted, and any of R to R4 represents 〇R7, wherein R7 is selected from the group consisting of hydrogen and C1-C4-. In the above chemical formula (1), it is also very preferable that m is 0; η is 0; Y represents a phenyl group substituted by a fluoro group, a gas group or a bromo group, or a secondary phenyl group, and R3 or R3 and R4 represents a hydroxyl group. In the above chemical formula (1), it is also very preferable that m is 0; η is 〇; γ represents a phenyl group which is substituted by a fluoro group at the 4 position, a gas group at the 4 position, and 2 to 4 at the 4 position. - The position is substituted by a fluoro group or substituted by a chloro group at the 2 and 4 positions, and R3 or R3 and R4 represent a hydroxy group. In the above Chemical Formula 1, it is particularly preferable; η is G; Υ represents a phenyl group which is substituted by a gas group, a gas group or a desert wire; or a secondary phenyl group; any one of R2 to R4 41 200932732 represents 〇R7 Wherein R7 is selected from the group consisting of hydrogen and CrC4-alkyl, and Ri represents fluorine. In the above formula (I), particularly preferably 111 is hydrazine; n is hydrazine; γ represents a phenyl group which is substituted at the 4-position by a fluoro group, at the 4 position by a gas group, at a position of 2_ and \ Substituted by a fluoro group or substituted with a chloro group at the 2_ and 4_ positions; any of γ 5 to & represents 〇R7, wherein R7 is selected from hydrogen and CrC4_alkyl; and R1 represents fluorine. In the above chemical formula (1), 特1 is 〇; 〇 is 〇; 丫 represents a phenyl group substituted by a fluoro group, a gas group or a bromo group; or a secondary phenyl group; R3 or R3 and R4 represent a hydroxyl group; R1 represents fluorine.在 10 In the above chemical formula (1), particularly preferred m is 〇; n is 〇; γ represents phenyl, 八 is substituted at the 4 position by a fluoro group, at the 4-position by a chloro group, at a 2_ and 4 position Substituted by a fluoro group or substituted with a gas group at the 2- and 4-positions; R3 or r3 and R4 represent a hydroxyl group; and R1 represents fluorine. Further, 'in the chemical formula (I), it is also preferred that Ri to R5 are selected from the group consisting of a hydroxyl group, a 15 methyl group, a mono-butyl group, a phenyl group, a methoxy group, an ethoxy group, a phenoxy group, an amine group, and a sulfur group. Base, hydroxyl, cyano, fluoro, carbyl, bromo, nitro, CF3, ocf3, pyridine, conh2, so2nh2, tetrazole or triazole. Further preferably, at least one of R1 to R5 is a saturated, unsaturated or aromatic heterocyclic ring which is optionally substituted one or more times by: CrC6-2 anthracene, CrC6-burning Oxyl, C00H, S03H, amine, sulfhydryl, hydroxy, nitro, cyano, fluoro, carbyl, bromo, decyl, CF3 or 〇cf3, or further substituted by One or more phenyl groups: Ci_C6_alkoxy, C〇〇H, SOgH, amine, sulfhydryl 'hydroxy, nitro, cyano, fluoro, carbyl, bromo, iodo Base, cf3 or ocf3. 42 200932732 Optionally, at least one of R1 to R5 is also preferably CONH2; so2NH2, or CONH24S02NH2, wherein the amine functionality is selected from

Crc6-烧基、C6-C1(r芳基或匕义『芳基_Ci c4烧基的殘基取代一次或多次。 5 I化學式(1)中，亦較佳者係Y代表苯基，其在鄰-及/或對-位置被下列各者取代：Ci_Q院氧基、C6_Ci〇_芳氧基、經基、硝基、胺基、CONH2、s〇2Nh2、氣代基、氣代基或 OCF3。甚至更佳者，Y代表苯基，其在鄰…間_及/或對位置 10 被取代一次、二次或三次，取代基係獨立地選自甲氧基、乙氧基、特-丁氧基、苯氧基、經基、确基、C〇NH2、S〇2NH2、氟代基、氣代基或〇CF3。亦較佳者係Y代表苯基，其在鄰-及/或對_位置被下列各者取代.C〗-C6_烧乳基、C6-Ci〇-芳氧基、經基、石肖基、 15 c〇NH2、so2nh2、氟代基、氯代基或OCF3。在化學式(I)中，亦較佳者係R1至R5選自曱基、特_丁基、苯基、曱氧基、乙氧基、苯氧基、胺基、硫氫基、經基、氰基、氟代基、氣代基、溴代基、硝基、cf3、ocf3、吡啶、CONH2、S〇2NH2、四唑、***或苯基，其進一步被 20 下列各者取代一或多次：Ci-CV烷氧基、COOH、S03H、胺基、硫氫基、經基、确基、氰基、氟代基、氣代基、溴代基、碘代基、CF3或OCF3 ;及Y代表苯基，其在鄰-及/或對_ 位置被下列各者取代：Ci_C6_烧氧基、CVCiQ-芳氧基、經基、硝基、conh2、so2nh2、氟代基、氣代基或〇cf3。 43 200932732 在又一任擇的實施例中，本發明係有關於具化學式(i) 的一化合物：Crc6-alkyl, C6-C1 (raryl or yttrium "aryl-Ci c4 alkyl residue substituted one or more times. 5 I chemical formula (1), also preferably Y represents phenyl, It is substituted at the ortho- and/or para-position by the following: Ci_Q, alkoxy, C6_Ci〇_aryloxy, thiol, nitro, amine, CONH2, s〇2Nh2, valence, gas Or OCF 3. Even better, Y represents a phenyl group which is substituted once, twice or three times at the position _ and/or at position 10, and the substituents are independently selected from the group consisting of methoxy, ethoxy, and -butoxy, phenoxy, thiol, decyl, C 〇 NH 2 , S 〇 2 NH 2 , fluoro, carbyl or hydrazine CF 3 . Also preferably Y represents phenyl, in o- and / Or the _ position is replaced by the following. C--C6_ succinyl, C6-Ci 〇-aryloxy, thiol, schiffyl, 15 c 〇 NH 2 , so 2 nh 2 , fluoro, chloro or OCF 3 . In the formula (I), it is also preferred that R1 to R5 are selected from the group consisting of an anthracenyl group, a tert-butyl group, a phenyl group, a decyloxy group, an ethoxy group, a phenoxy group, an amine group, a sulfhydryl group, a thiol group, Cyano, fluoro, carbyl, bromo, nitro, cf3, ocf3, pyridine, CONH 2. S〇2NH2, tetrazole, triazole or phenyl, which is further substituted by one or more of the following: Ci-CV alkoxy, COOH, S03H, amine, sulfhydryl, thiol, indeed a cyano group, a cyano group, a fluoro group, a carbyl group, a bromo group, an iodo group, a CF3 or OCF3; and Y represents a phenyl group which is substituted at the ortho- and/or _ position by the following: Ci_C6_ Oxyl, CVCiQ-aryloxy, thiol, nitro, conh2, so2nh2, fluoro, valyl or 〇cf3. 43 200932732 In yet another alternative embodiment, the invention relates to a chemical formula (i a compound:

=X)n—(CH2)m—Y ⑴ 5 其中 R1至R5係彼此獨立地代表：=X)n—(CH2)m—Y (1) 5 where R1 to R5 are independently of each other:

氫；hydrogen;

Ci-C6_烧基、C3-C8-環烧基、C6-Ci〇-芳基、CVCio-芳基-CrC8-烷基、CVCV烷氧基、c6-c1()-芳氧基、c6-c10-芳 10 基-CrC8-烷氧基、Ci-CV烷氧基羰基、c6-c1(r芳氧基羰基、C6-C1(r芳基-Q-CV烷氧基羰基、CVCV烷基羰基、 C6_Ci〇-芳基幾基、C6-Ci〇-芳基-Ci_C8-烧基叛基、Ci_C6_烧基羧基、c6-c1()-芳基羧基、Q-CV烷基氫硫基、c6-c10-芳基氫硫基、crc6-烷基酼基羰基、c3-c8-環烷基巯基羰 15 基、C6-Ci〇-芳基硫基獄基、Ci-C6-烧基Μ基缓基、C6-Ci〇_ 芳基巯基羧基、CVC6-烷基磺醯基、C6-C1()-芳基磺醯基、 crc6-烷基氧硫基、c6-c1(r芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次：Ci-C6_alkyl, C3-C8-cycloalkyl, C6-Ci〇-aryl, CVCio-aryl-CrC8-alkyl, CVCV alkoxy, c6-c1()-aryloxy, c6- C10-Aryl 10-yl-CrC8-alkoxy, Ci-CV alkoxycarbonyl, c6-c1 (r aryloxycarbonyl, C6-C1 (raryl-Q-CV alkoxycarbonyl, CVCV alkylcarbonyl) , C6_Ci〇-aryl, C6-Ci〇-aryl-Ci_C8-alkyl group, Ci_C6_alkyl carboxyl group, c6-c1()-arylcarboxy group, Q-CV alkyl thiol group, c6 -c10-arylhydrothiol, crc6-alkylmercaptocarbonyl, c3-c8-cycloalkylcarbonylcarbonyl15, C6-Ci〇-arylthiol, Ci-C6-alkylthiol , C6-Ci〇_ arylsulfonylcarboxy, CVC6-alkylsulfonyl, C6-C1()-arylsulfonyl, crc6-alkyloxythio, c6-c1 (raryloxythio) , each of which is optionally replaced one or more times by:

CrC6-烷基；Q-CV烷氧基；c6-c10-芳氧基； 20 co2h ; so3h ; conh2 ; so2nh2 ; conh2 或 so2nh2，其中該胺基官能度被選自crc6-烷基、c6-c1(r芳基或 c6-c10-芳基-crc4-烷基的殘基取代一次或多次，及其中 44 200932732 在一種經二-CVC6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6-烷基、C6-C10-芳基、C6-Ci〇-方基-C1-C4-烧基、Ci-Cr 烧基幾基、C6-Ci〇-5 芳基羰基、crc6-烷基磺醯基及c6-c1()-芳基磺醯基；硫氫基；經基；琐基；氰基；氟代基；氯代基；溴代基；代基，CF3或〇CF3， co2H;CrC6-alkyl; Q-CV alkoxy; c6-c10-aryloxy; 20 co2h; so3h; conh2; so2nh2; conh2 or so2nh2, wherein the amine functionality is selected from the group consisting of crc6-alkyl, c6-c1 Substituting one or more residues of (raryl) or c6-c10-aryl-crc4-alkyl, and wherein, in the case of a di-CVC6-alkyl substituted amine functionality, the alkane The base residues may be combined to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of CrC6-alkyl, C6-C10-aryl, C6-Ci〇 - aryl-C1-C4-alkyl, Ci-Cr alkyl, C6-Ci〇-5 arylcarbonyl, crc6-alkylsulfonyl and c6-c1()-arylsulfonyl; sulfur Hydrogen group; thiol group; cyano group; fluoro group; chloro group; bromo group; alkenyl group, CF3 or hydrazine CF3, co2H;

10 15 so3h ; 胺基；經選自下列群中的殘基取代一或多次之胺基：Q-CV 院基、C6_Ci〇_芳基、C6-Ci〇-芳基-Ci_C6-烧基、Ci_C6-烧基羰基、c6-c1(r芳基羰基、CVCV烷基磺醯基及c6-c1()-芳基磺醯基；具下列化學式(II)之一種經二取代的胺基：10 15 so3h ; Amino; an amine group substituted one or more times with a residue selected from the group consisting of Q-CV, C6_Ci〇_aryl, C6-Ci〇-aryl-Ci_C6-alkyl, Ci_C6-alkylcarbonyl, c6-c1 (rarylcarbonyl, CVCV alkylsulfonyl and c6-c1()-arylsulfonyl; a disubstituted amino group of the following formula (II):

-N W Ο (II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-C6-烷基，及其中化學式(II)中的亞甲基可選擇性地被(^-(：6-烷基、氟代基或氯代基取代一或二次； 20 CONH2 ; so2nh2 ； C0NH4S02NH2，其中該胺基官能度被選自crc6-烷基、C6-C1(r芳基或C6-C1G-芳基-CrCV烷基的殘基取代一或 45 200932732 二次，及其中在一種經二-CrCV烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；硫氫基；經基； 5 硝基；氰基；氟磺醯基；選自氟代基、氣代基、溴代基或峨代基之齒素； CF3 ; 10 15 20-NW Ο (II) wherein 〇 represents 0 or 1, and W represents oxygen, CH2 or NR6, and R6 is selected from hydrogen and Q-C6-alkyl, and the methylene group in the formula (II) is optionally Substituted by (^-(:6-alkyl, fluoro or chloro) one or two; 20 CONH2; so2nh2; C0NH4S02NH2, wherein the amine functionality is selected from the group consisting of crc6-alkyl, C6-C1 (r The residue of an aryl or C6-C1G-aryl-CrCV alkyl group is substituted by one or 45 200932732 twice, and in the case of an amine functional group substituted with a di-CrCV alkyl group, the alkyl residue may be Binding to form a 5- or 6-membered ring; sulfhydryl; a sulfhydryl group; a nitro group; a cyano group; a fluorosulfonyl group; a dentate selected from the group consisting of a fluoro group, a gas group, a bromo group or a thio group; ; 10 15 20

OCF3 ;或 -種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統’其選擇性地被下列各者取代一或多次； Q-CV 烷基，CrC6-烷氧基；c〇〇H ; s〇 h CONH2 ; SANK2 ; CON%或sow%，其中該胺基官能度被選ICrC6-烧基、C6-Cl〇_芳基或c6_Ci。芳基_c々烷基的殘基取代一次或多次，及其中在一種經二OCF3; or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms' which is optionally substituted one or more times by the following: Q-CV alkyl, CrC6-alkoxy ; c〇〇H ; s〇h CONH2 ; SANK2 ; CON% or sow%, wherein the amine functionality is selected from ICrC6-alkyl, C6-Cl〇-aryl or c6_Ci. The aryl-c々 alkyl residue is substituted one or more times, and

烧基取代的胺基官能度之情況下，觀基殘基可結合^ 形成5或6員環；胺基；經選自下列群中的殘基取代—或多次之胺基：CVQ-烷基、C6_Ci。芳基、C6_Ci。芳基 -CVC4-烷基、Cl-CV烷基幾基、以〇芳基羰基^In the case of a decyl-substituted amine functionality, the benzyl group may be bonded to form a 5 or 6 membered ring; an amine group; substituted with a residue selected from the group consisting of - or multiple amine groups: CVQ-alkane Base, C6_Ci. Aryl, C6_Ci. Aryl-CVC4-alkyl, Cl-CV alkyl group, fluorenyl aryl group ^

Cl-C6-烧基續醯基及cvClQ_芳基㈣基；錢基；輕基；琐基；氰基；氟代基；氣代基；溴代基4代基； CF3 或 OCF3 ; 及其中R至R中之任二或多者可結合而形成稠合的飽 46 200932732 和、不飽和或芳族同環或雜環系統； η代表0 ; m代表1 ; Y代表苯基，其選擇性地被下列各者取代一或多次： a) Ci-C6_ 烧基、C6-Ci。-方基、C6-Ci。-芳基-Ci_C8-烧 5 基、Ci_C6-烧乳基、C6-Ci。-芳乳基、C6-Ci〇-芳基-Ci_C8-烧氧基、crc6-烷氧基羰基、c6-c1(r芳氧基羰基、c6-c10-芳基-crc8-烷氧基羰基、crc6-烷基羰基、c6-c1()-芳基羰基、c6-c1()-芳基-crc8-烷基羰基、crc6-烷基羧基、 ® c6-c1Q-芳基羧基、crc6-烷基氫硫基、c6-c1(r芳基氫硫 10 基、crc6-烷基毓基羰基、c3-c8-環烷基巯基羰基、 ’ C6-C1()-芳基巯基羰基、CrC6-烷基毓基羧基、C6-Ckt芳基 - Μ基羧基、CrC6-烷基磺醯基、C6-C1(r芳基磺醯基、Cl-C6-alkyl group and cvClQ_aryl (tetra) group; Qianji; light base; tribasic; cyano; fluoro group; gas group; bromo group 4 base; CF3 or OCF3; Any two or more of R to R may be combined to form a fused saturated 46 200932732 and an unsaturated or aromatic homocyclic or heterocyclic ring system; η represents 0; m represents 1; Y represents a phenyl group, and its selectivity The ground is replaced by one or more of the following: a) Ci-C6_ alkyl, C6-Ci. - Square base, C6-Ci. -Aryl-Ci_C8-calcined 5 base, Ci_C6-calcined base, C6-Ci. - aryl aryl, C6-Ci 〇-aryl-Ci_C8-alkoxy, crc6-alkoxycarbonyl, c6-c1 (r aryloxycarbonyl, c6-c10-aryl-crc8-alkoxycarbonyl, Crc6-alkylcarbonyl, c6-c1()-arylcarbonyl, c6-c1()-aryl-crc8-alkylcarbonyl, crc6-alkylcarboxy, ® c6-c1Q-arylcarboxy, crc6-alkyl Hydrogenthio, c6-c1 (rarylhydrosulfuryl 10, crc6-alkylmercaptocarbonyl, c3-c8-cycloalkylfluorenylcarbonyl, 'C6-C1()-aryldecylcarbonyl, CrC6-alkyl Mercaptocarboxy, C6-Ckt aryl-fluorenylcarboxy, CrC6-alkylsulfonyl, C6-C1 (rarylsulfonyl,

CrQ-烷基氧硫基、C6-C1()-芳基氧硫基；其中各者選擇性地被下列各者取代一或多次： 15 CrC6-烷基；CVCV烷氧基；選擇性地被CVCV烷基取代一或二次之 conh2 或 so2nh2 ; so3h ; C02H ;胺 ® 基；經選自下列群中的殘基取代一或多次之胺基：CrQ-alkyloxythio, C6-C1()-aryloxythio; each of which is optionally substituted one or more times by: 15 CrC6-alkyl; CVCV alkoxy; optionally Subh2 or so2nh2; so3h; C02H; amine® group substituted by CVCV alkyl; one or more amine groups substituted with a residue selected from the group consisting of:

Ci-C6-烧基、C6-Ci〇-方基、C6-Ci〇-方基-C1-C4-娱》基、 CrC6-烷基羰基、C6-C1()-芳基羰基、CVCV烷基磺醯基 20 及C6-C1Q-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；CF3或OCF3 ; 其中該等選擇性取代基中之數者可結合而形成稍合的飽和、不飽和或芳族同環或雜環系統；或 b) —種由至多10個原子組成之飽和、不飽和或芳族雜 47 200932732 環式環系統，其選擇性地被下列各者取代一或多次： Crc6-烷基；CrC6-烷氧基；COOH ;選擇性地被CrC6-烷基取代一或二次之conh2或so2nh2 ; so3h ;胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、 5 C6-C1()-芳基、C6-C10-芳基-CVC4-烷基、crc6-烷基羰基、 c6-c1(r芳基羰基、CkCV烷基磺醯基及c6-c1(r芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；CF3或OCF3 ;或Ci-C6-alkyl, C6-Ci〇-square, C6-Ci〇-square-C1-C4-Enteryl, CrC6-alkylcarbonyl, C6-C1()-arylcarbonyl, CVCV alkyl Sulfomethyl 20 and C6-C1Q-arylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; chloro; bromo; iodo; CF3 or OCF3; a plurality of optional substituents may be combined to form a slightly saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; or b) a saturated, unsaturated or aromatic heteroatom consisting of up to 10 atoms. 200932732 Ring ring system, which is optionally substituted one or more times by: Crc6-alkyl; CrC6-alkoxy; COOH; conh2 or so2nh2 selectively substituted by CrC6-alkyl one or two times ; a3h; Amino; an amine group substituted one or more times with a residue selected from the group consisting of: crc6-alkyl, 5 C6-C1()-aryl, C6-C10-aryl-CVC4-alkyl , crc6-alkylcarbonyl, c6-c1 (rarylcarbonyl, CkCV alkylsulfonyl and c6-c1 (rarylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; a gas radical; a bromo group; an iodo group; a CF3 or OCF3; or

C)羥基；硫氫基；硝基；氰基；氟代基；氣代基；溴 10 代基；碘代基；cf3 ; ocf3 ; co2h ; so3h ; CONH2 ; so2nh2 ; CONH2或S02NH2，其中該胺基官能度被選自 C!-C6-烧基、C6-Ci〇-^基或C6-Ci〇-方基-C1-C4-烧基的殘基取代一次或多次，及其中在一種經二-Ci-Ce-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環； 15 胺基；經選自下列群中的殘基取代一或多次之胺基： Ci_C6_ 烧基、C6-Ci〇-芳基、C6-Ci〇-芳基-Ci_C8_ 烧基、 crc6-烷基羰基、C6-C1G-芳基羰基、CVCV烷基磺醯基及 c6-c1Q-芳基磺醯基；具下列化學式(IV)之一種經二取代的胺基：C) hydroxy; sulfhydryl; nitro; cyano; fluoro; aldehyde; bromo 10; iodo; cf3; ocf3; co2h; so3h; CONH2; so2nh2; CONH2 or S02NH2, wherein the amine The base functionality is substituted one or more times by a residue selected from the group consisting of C!-C6-alkyl, C6-Ci〇-^ or C6-Ci〇-aryl-C1-C4-alkyl, and In the case of a di-Ci-Ce-alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; 15 an amine group; one or more substituted with a residue selected from the group consisting of Amino group: Ci_C6_ alkyl, C6-Ci〇-aryl, C6-Ci〇-aryl-Ci_C8_ alkyl, crc6-alkylcarbonyl, C6-C1G-arylcarbonyl, CVCV alkylsulfonyl and a c6-c1Q-arylsulfonyl group; a disubstituted amino group having the following chemical formula (IV):

—N W 20 °(IV) 其中0代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-Cr烷基，及其中化學式(IV)中的亞曱基可選擇性地被心名^烷基、氟代基或氣代基取代一或二次； 48 200932732 5 Ο 10 15 ❹ 20 前提在於若Rl、R2及R5代表氫，R4代表氫、三氟甲氧基、二氟丁氧基、3,3,5,5-四甲基環己氧基、苄氧基、苯氧基、苯基、2-二甲基胺基乙氧基或3_甲基苯氧基_甲基，及 R3代表氫、三氟甲氧基、三氟丁氧基、3,3,5 5_四甲基環己氧基、苯氧基、4_氣苯氧基、環己基、苯基、嗎啉磺醯基、3,3,5-三甲基環己基胺基磺醯基、2,2 6,6_四甲基哌啶 -4-基胺基績醯基、2_(二異丙基胺基乙基）胺基磺醯基、4_ 甲基哌嗪-1-基-磺醯基、3,3_二甲基哌啶羰基或3,5二氣苯氧基、2-二甲基胺基乙氧基或3_甲基苯氧基_甲基；則γ並非代表未經取代的苯基。甚至更佳者’ Y代表苯基，其被下列各者取代一或多次：cvq-烧基；苯基；CrCV^氧基；經基；氟代基；氣代基，肩代基，CF3 ; 〇CF3 ;胺基；或選擇性地被c^-CV 院基取代一或二次之c〇nh2*so2nh2，其中該等選擇性的 CrCV烷基殘基可結合而形成5或6員環。又更佳者係m代表〇，及γ代表被羥基、氟代基、氣代基或溴代基取代一或二次之苯基。最佳m代表〇，及γ代表苯基，其在4_位置被氟代基取代、在4-位置被氣代基取代、在2-與4-位置被氟代基取代、在2-與4-位置被氣代基取代或在4-位置被苯基取代。在上述的化學式(I)中，特佳m為〇 ; η為〇 ; γ代表被氟代基、氯代基或漠代基取代一或二次之苯基；及R2至R4中之任一者代表OR7，其中R7係選自氫與Ci_C4烷基。—NW 20 °(IV) wherein 0 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and Q-Cr alkyl, and the fluorenyl group in the formula (IV) is optionally Substituted by the name alkyl, fluoro or ke group for one or two times; 48 200932732 5 Ο 10 15 ❹ 20 The premise is that if Rl, R2 and R5 represent hydrogen, R4 represents hydrogen, trifluoromethoxy, Fluorinoxy, 3,3,5,5-tetramethylcyclohexyloxy, benzyloxy, phenoxy, phenyl, 2-dimethylaminoethoxy or 3-methylphenoxy _Methyl, and R3 represents hydrogen, trifluoromethoxy, trifluorobutoxy, 3,3,5 5 -tetramethylcyclohexyloxy, phenoxy, 4-phenoxy, cyclohexyl, Phenyl, morpholinsulfonyl, 3,3,5-trimethylcyclohexylaminosulfonyl, 2,2 6,6-tetramethylpiperidin-4-ylamine, 2_( Diisopropylaminoethyl)aminosulfonyl, 4-methylpiperazin-1-yl-sulfonyl, 3,3-dimethylpiperidinylcarbonyl or 3,5 diphenoxyphene, 2 -Dimethylaminoethoxy or 3-methylphenoxy-methyl; then y represents not an unsubstituted phenyl group. Even better, 'Y stands for phenyl, which is substituted one or more times by: cvq-alkyl; phenyl; CrCV^oxy; thiol; fluoro; gas, shoulder, CF3 〇CF3; an amine group; or c〇nh2*so2nh2 optionally substituted by a c^-CV substituent, wherein the selective CrCV alkyl residues may combine to form a 5 or 6 membered ring . More preferably, m represents hydrazine, and γ represents a phenyl group substituted one or two times with a hydroxy group, a fluoro group, an oxyl group or a bromo group. Preferably, m represents 〇, and γ represents phenyl, which is substituted at the 4 position by a fluoro group, at the 4-position by a gas group, at the 2- and 4-positions by a fluoro group, at a 2-position The 4-position is substituted by a gas group or by a phenyl group at the 4-position. In the above formula (I), particularly preferably m is hydrazine; η is hydrazine; γ represents a phenyl group substituted one or two times with a fluoro group, a chloro group or a molybdenyl group; and any one of R2 to R4 Represents OR7 wherein R7 is selected from the group consisting of hydrogen and Ci_C4 alkyl.

在上述的化學式(I)中’亦非常佳者係m為〇 ; η為0 ; Y 49 200932732 代表笨基，其在4-位置被氟代基取代、在4_位置被氣代基取代、在2-與4-位置被氟代基取代或在2_與4_位置被氣代基取代，及R2至R4中之任一者代表〇R7，其中R7係選自氫與 C1-C4、院基。 5 10 15 20 在上述的化學式⑴中，亦非常佳者係〇1為〇 ; 11為〇 ; γ 代表被氟代基、氣代基或溴代基取代—或二次之苯基，及 R3或者R3與R4代表羥基。 ❹ 在上述的化學式⑴中，亦非常佳者係爪為〇 ; 11為〇 ; γ 代表苯基，其林位置被氟代基取代、在4位置被氣代基取代、在2-與4-位置被氟代基取代或在2_鉢位置被氯代基取代，及R3或者R3與R4代表羥基。在上述的化學式附，特佳; γ代表被氣代基、氣代基或純基取代—或二次之苯基；r^r4中之任-者代表OR7’其中r7係選自氫與Ci_C4減；及^代表氟。在上述的化學式⑴中，特佳_〇;4〇; γ代表苯基 ❹ 其在4-位置被氟代基取代、在4_位置被氣代基取代、在: 與4-位置被紐絲代或社與4_位置魏代基取代；f ^中，任—者代表〇r7’其中r7係選自氫與c】_c^ 基；及R1代表氟。在上述的化學切)巾，縣_G;n為G; 二=基或溴代基取代—或二次之苯基;r3或納 R代表羥基；及R1代表氟。在上述的化學式(1)中，特佳4〇;n為0; Y代表苯基 50 200932732 其在4-位置被氟代基取代、在4_位置被氯代基取代、在2_ 與4-位置被氟代基取代或在2_與4位置被氯代基取代；R3 或者R3與R4代表羥基；及Ri代表氟。 5 Ο 10 15 ❹ 20 而且’在化學式⑴中，亦較佳者係Ri至R5選自甲基；特-丁基；苯基；甲氧基；乙氧基；苯氧基；胺基；硫氫基；經基’氰基；氟代基；氯代基；溴代基；硝基；Cf3 ; 〇Cf3 ; 吼啶；CONH2或SC^NH2，其中該胺基官能度被選自Cl_C6_ 烷基、C6-C10-芳基或cvCht芳基-q-CV烷基的殘基取代一次或多次；四η坐或三0坐。 R1至R5中之任一者亦較佳為笨基，其進一步被下列各者取代一或多次：CrCV烷氧基、c〇〇H、s〇3h、胺基、硫氫基、羥基、硝基、氰基、氟代基、氯代基、溴代基、碘代基、CF3或ocf3。在化學式⑴中，亦較佳者係Y代表苯基，其在鄰-及/或對-位置被下列各者取代：crc6_烷氧基、C6_CiQ_芳氧基、羥基、硝基、胺基、CONH2、S〇2NH2、氟代基、氯代基或〇CF3。甚至更佳者，Y代表苯基在鄰_、間_及/或對_位置被取代一次、二次或三次，取代基係獨立地選自甲氧基、乙氧基、特-丁氧基、苯氧基、經基、確基、c〇NH2、s〇2NH2、氟代基、氣代基或〇CF3。在化學式(I)中，Y亦較佳代表苯基，其在鄰及/或對_ 位置被下列各者取代：CVC6-烷氧基、c6-Ch)-芳氧基、羥基、硝基、CONH2、S〇2NH2、I代基、氯代基或0CF3。在化學式⑴中，亦非常佳者係R1至R5選自曱基、特-丁 51 200932732 基、苯基、甲氧基、乙氧基、苯氧基、胺基、硫氫基、羥基、氰基、氟代基、氣代基、溴代基、硝基、CF3、〇cf3、吡啶、conh2、so2nh2、四唑、***或苯基’其進一步被下列各者取代一或多次：CrC6-烷氧基、COOH、S03H、胺 5 基、硫氫基、羥基、硝基、氰基、氟代基、氣代基、溴代基、碘代基、CF3或OCF3 ;及Y代表苯基，其在鄰-及/或對-位置被下列各者取代：q-CV烷氧基、c6-c1(r芳氧基、羥基、硝基、conh2、so2nh2、氟代基、氣代基或ocf3。在第一個非常佳的實施例中，本發明係有關於具化學 © 10 式⑴的一化合物：In the above formula (I), 'very good' is that m is 〇; η is 0; Y 49 200932732 represents a stupid group which is substituted at the 4-position by a fluoro group and at the 4 position by a gas group. Substituting at the 2- and 4-positions with a fluoro group or at the 2 and 4 positions with a gas group, and R2 to R4 for 〇R7, wherein R7 is selected from hydrogen and C1-C4, Court base. 5 10 15 20 In the above chemical formula (1), it is also very preferable that 〇 1 is 〇; 11 is 〇; γ represents a fluoro group, a gas group or a bromo group substituted or a secondary phenyl group, and R 3 Or R3 and R4 represent a hydroxyl group. ❹ In the above chemical formula (1), it is also very good that the claw is 〇; 11 is 〇; γ represents phenyl, the forest position is replaced by a fluoro group, and the gas position is substituted at the 4-position, at 2- and 4- The position is substituted by a fluoro group or by a chloro group at the 2_钵 position, and R3 or R3 and R4 represent a hydroxy group. In the above chemical formula, it is particularly preferable; γ represents a phenyl group substituted by a gas group, a gas group or a pure group or a second group; any of r^r4 represents OR7' wherein the r7 system is selected from hydrogen and Ci_C4 Subtract; and ^ represents fluorine. In the above chemical formula (1), particularly preferably 〇〇; 4 〇; γ represents a phenyl hydrazone which is substituted at the 4-position by a fluoro group, at the 4 position by a gas group, at: 4-position with a nucleus Substituted or substituted with 4_ position Weidike; f ^, any - represents 〇r7' wherein r7 is selected from hydrogen and c) _c^; and R1 represents fluorine. In the above chemically cut), the county _G; n is G; the quaternary or bromo substituted or the secondary phenyl; the r3 or the nano R represents a hydroxyl group; and R1 represents fluorine. In the above formula (1), particularly preferred is 4; n is 0; Y represents phenyl 50 200932732 which is substituted at the 4-position by a fluoro group, at the 4 position by a chloro group, at 2_ and 4- The position is substituted by a fluoro group or by a chloro group at positions 2 and 4; R3 or R3 and R4 represent a hydroxyl group; and Ri represents fluorine. 5 Ο 10 15 ❹ 20 and 'in the chemical formula (1), it is also preferred that Ri to R5 are selected from methyl; tert-butyl; phenyl; methoxy; ethoxy; phenoxy; amine; Hydrogen; thiol; fluoro; chloro; bromo; nitro; Cf3; 〇Cf3; acridine; CONH2 or SC^NH2, wherein the amine functionality is selected from the group consisting of Cl_C6_alkyl The residue of the C6-C10-aryl or cvCht aryl-q-CV alkyl group is substituted one or more times; four η sitting or three zero sitting. Any of R1 to R5 is also preferably a stupid group, which is further substituted by one or more of the following: CrCV alkoxy group, c〇〇H, s〇3h, amine group, sulfhydryl group, hydroxyl group, Nitro, cyano, fluoro, chloro, bromo, iodo, CF3 or ocf3. In the chemical formula (1), it is also preferred that Y represents a phenyl group which is substituted at the ortho- and/or p-position by the following: crc6-alkoxy, C6_CiQ_aryloxy, hydroxy, nitro, amine , CONH2, S〇2NH2, fluoro, chloro or hydrazine CF3. Even more preferably, Y represents a phenyl group which is substituted once, twice or three times at the o-, m-, and/or p-positions, and the substituents are independently selected from the group consisting of methoxy, ethoxy, and t-butoxy. , phenoxy, thiol, decyl, c 〇 NH 2 , s 〇 2 NH 2 , fluoro, carbyl or hydrazine CF 3 . In the formula (I), Y also preferably represents a phenyl group which is substituted at the ortho and/or p-position by: CVC6-alkoxy, c6-Ch)-aryloxy, hydroxy, nitro, CONH2, S〇2NH2, I group, chloro group or 0CF3. In the chemical formula (1), it is also preferred that R1 to R5 are selected from the group consisting of fluorenyl, tert-butyl 51 200932732, phenyl, methoxy, ethoxy, phenoxy, amine, sulfhydryl, hydroxy, cyanide Base, fluoro, carbyl, bromo, nitro, CF3, 〇cf3, pyridine, conh2, so2nh2, tetrazole, triazole or phenyl' which are further substituted one or more times by: CrC6 - alkoxy, COOH, S03H, amine 5, sulfhydryl, hydroxy, nitro, cyano, fluoro, carbyl, bromo, iodo, CF3 or OCF3; and Y represents phenyl , which is substituted at the ortho- and/or para-position by the following: q-CV alkoxy, c6-c1 (r aryloxy, hydroxy, nitro, conh2, so2nh2, fluoro, valyl or Ocf3. In a first very preferred embodiment, the invention relates to a compound of formula (1):

0—(C=X)n—(CH2)m—Y (I) 其中R1或R5為氫或氟； R2至R4中之任一者代表羥基，而其他尺殘基為： 15 氫； ❹0—(C=X)n—(CH2)m—Y (I) wherein R1 or R5 is hydrogen or fluorine; any of R2 to R4 represents a hydroxyl group, and the other residue is: 15 hydrogen;

Cl_C6_院基、C3_C8-環燒基、C6-C1(r芳基、c6_Cl0_芳基-CrC8-烧基、Cl_C6_燒氧基、C6_Ci『芳氧基、C6_Ci〇_芳基-q-cv炫氧基、Ci_C6_烧氧基獄基、C6_Ci〇芳氧基羰基、C6-c1(r芳基_Cl_C8_烷氧基羰基、Ci_C6烷基羰基、 20 C6_Cl0·芳基幾基、芳基-crc8-烧基幾基、Cl_c6i 基叛基、c6-c10-芳基叛基、Ci_c6_烧基氣硫基、『芳基虱硫基、cvcv·烷基巯基羰基、C3_C8_環烷基巯基羰 52 200932732 基、C6-C1()-芳基疏基魏基、CkQ-烧基髄基竣基、c6-C1()-芳基Μ基缓基、Ci-CV烧基續醢基、C6-Ci〇-芳基績酿基、 Ci-C6_烧基氧硫基、C6-C1(r芳基氧疏基’其中各者選擇性地被下列各者取代一次或多次：Ci_C6_烧基、Ci-Cg-烧氧 5 基、C6-C10-芳氧基、CO2H、S03H、胺基、CVC6-燒基胺基、二-C〗-C6_烧基胺基、硫氫基、經基、硝基、氣基、氟代基、氣代基、溴代基、碘代基、CF3或OCF3 ; co2H ; so3h ; 10 胺基；經選自下列群中的殘基取代一或多次之胺基：Ci-CV 烧基、C6-C1()-芳基、Q-q。-芳基-CVC6-烧基、CrC6-烧基羰基、C6-C1(r芳基羰基、CnCV烷基磺醯基及C6-C10-芳基磺醯基； 15Cl_C6_院, C3_C8-cycloalkyl, C6-C1 (r aryl, c6_Cl0_aryl-CrC8-alkyl, Cl_C6_alkoxy, C6_Ci "aryloxy, C6_Ci〇_aryl-q-cv Decyloxy, Ci_C6_alkyloxyphenyl, C6_Ci〇aryloxycarbonyl, C6-c1 (raryl_Cl_C8_alkoxycarbonyl, Ci_C6 alkylcarbonyl, 20 C6_Cl0.aryl, aryl- Crc8-alkyl group, Cl_c6i group, c6-c10-aryl group, Ci_c6_alkylthio group, "arylsulfonylthio group, cvcv.alkylmercaptocarbonyl group, C3_C8_cycloalkylcarbonylcarbonyl 52 200932732 】, C6-C1()-aryl sulfhydryl-based, CkQ-alkyl fluorenyl, c6-C1()-aryl fluorenyl, Ci-CV alkyl thiol, C6- Ci〇-aryl aryl, Ci-C6_alkyloxythio, C6-C1 (raryloxycarbyl) each of which is optionally substituted one or more times by: Ci_C6_alkyl ,Ci-Cg-Oxygenated 5-yl, C6-C10-aryloxy, CO2H, S03H, Amine, CVC6-alkylamino, Di-C-C6-alkylamino, sulfhydryl, thiol , nitro, carbyl, fluoro, carbyl, bromo, iodo, CF3 or OCF3; co2H; so3h; 10 amine; residue selected from the group below Substituting one or more amine groups: Ci-CV alkyl, C6-C1()-aryl, Qq.-aryl-CVC6-alkyl, CrC6-alkylcarbonyl, C6-C1 (rarylcarbonyl, CnCV alkylsulfonyl and C6-C10-arylsulfonyl; 15

具下列化學式（II)之一種經二取代的胺基：a disubstituted amino group of the following formula (II):

Ή7] °(11) 其中0代表0或1，而W代表氧、CH2或NR6，R6係選自氫與CrC6-烷基，及其中化學式(II)中的亞曱基可選擇性地被(^-(1;6-烧基、氟代基或氣代基取代一或二次； conh2 ； S02NH2; conh2或so2nh2，其中該胺基官能度被選自crc6-烷基、C6-C1(r芳基或C6-C1(r芳基-crc6-烷基的殘基取代一次 53 20 200932732 或多次’及其中在一種經二-q-c^烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；硫SL基；羥基； 5 硝基；氰基；氟績酿基；選自氟代基、氣代基、溴代基或碘代基之_素； CF3 ; ❹ 10 OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次：烧基、CrCV院氧基、COOH、S〇3H、胺基、硫氫基、經基、硝基、氰基、氟代基、氣代基、溴代基、碘代基、 15 cf3 或 ocf3 ; 及其中R2至R4中之二或多者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統； 0 η與m為0 ;及 y為苯基，其被下列各者取代一或多次：crc6-烷基； 20 苯基；Cl_C6-烷氧基；羥基；氟代基；氣代基；溴代基； CF3 ; OCF3 ;胺基；或選擇性地被(^^^烷基取代一或二次之CONH2 ’其中該等選擇性的Cl_C6_烷基殘基可結合而形成5或6員環；或其一種立體異構物、藥學上可接受的鹽類或酯或前 54 200932732 驅藥物。在第二個非常佳的實施例中，本發明係有關於具化學式(I)的一化合物： R2 R3Ή7] °(11) wherein 0 represents 0 or 1, and W represents oxygen, CH2 or NR6, and R6 is selected from hydrogen and CrC6-alkyl, and wherein the fluorenyl group in the formula (II) is selectively ^-(1;6-alkyl, fluoro or ke group substituted one or two times; conh2; S02NH2; conh2 or so2nh2, wherein the amine functionality is selected from the group consisting of crc6-alkyl, C6-C1 (r The aryl or C6-C1 (raryl-crc6-alkyl residue is substituted once 53 20 200932732 or multiple times and in the case of a bis-qc^alkyl substituted amine functionality, the alkane The base residue may be combined to form a 5 or 6 membered ring; a sulfur SL group; a hydroxyl group; a 5 nitro group; a cyano group; a fluoro group; a fluoro group, a gas group, a bromo group or an iodo group. a CF3; ❹ 10 OCF3; or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, which is optionally substituted one or more times by: calcination, CrCV Base, COOH, S〇3H, amine, sulfhydryl, thiol, nitro, cyano, fluoro, carbyl, bromo, iodo, 15 cf3 or ocf3; and R2 to R4 thereof Two or more of them can be combined to form a thick a saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; 0 η and m are 0; and y is phenyl which is substituted one or more times by the following: crc6-alkyl; 20 phenyl; Cl_C6- Alkoxy; hydroxy; fluoro; ketone; bromo; CF3; OCF3; amine; or optionally substituted by (^^^alkyl, one or two of CONH2' The Cl_C6_alkyl residue may be combined to form a 5 or 6 membered ring; or a stereoisomer thereof, a pharmaceutically acceptable salt or ester thereof or a pro-drug 2009 200932732. In a second very preferred embodiment The invention relates to a compound of formula (I): R2 R3

R4 R5 5 (I) 其中R1或R5為氫或氟；〇 R2至R4中之任一者代表胺基，而其他R殘基為：氫；R4 R5 5 (I) wherein R1 or R5 is hydrogen or fluorine; 〇 any of R2 to R4 represents an amine group, and the other R residues are: hydrogen;

Ci-CV烧基、C3-C8-環烧基、C6-Ci〇-芳基、C6_Ci〇-芳 -10 基-Ci_ C8-院基、Ci_C6_ 院氧基、C6_Ci〇-芳氧基、CVCh)-芳基-Ci-CV烷氧基、crc6-烷氧基羰基、c6-c1()-芳氧基羰基、C6-C1(r芳基-CrCV烷氧基羰基、Q-CV烷基羰基、 C6-C1(r芳基羰基、C6-C1()-芳基-(VCV烷基羰基、crc6-烷基羧基、c6-c10-芳基羧基、crc6-烷基氫硫基、c6-c10-芳 ® 15 基氫硫基、crc6-烷基酼基羰基、c3-c8-環烷基巯基羰基、c6-c1(r芳基酼基羰基、CrC6-烷基巯基羧基、c6-c10-芳基毓基羧基、CVCV烷基磺醯基、c6-c1()-芳基磺醯基、 CVCV烷基氧硫基、c6-c1(r芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次：CrC6-烷基、CVC6-烷氧 20 基、c6-c1(r芳氧基、C02H、S03H、胺基、crc6-烷基胺基、二-Ci_C6_烧基胺基、硫氫基、經基、確基、氰基、氟代基、氯代基、溴代基、碘代基、CF3或OCF3 ; 55 200932732 co2h ； so3H; 胺基； 5 經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、C6-C10-芳基、C6-C1()-芳基-CVCV烷基、Ci-CV烷基羰基、c6-c10-芳基羰基、crc6-烷基磺醯基及c6-c1(r芳基磺醯基；具下列化學式（II)之一種經二取代的胺基：Ci-CV alkyl, C3-C8-cycloalkyl, C6-Ci〇-aryl, C6_Ci〇-aryl-10-Ci_C8-hospital, Ci_C6_ alkoxy, C6_Ci〇-aryloxy, CVCh) -aryl-Ci-CV alkoxy, crc6-alkoxycarbonyl, c6-c1()-aryloxycarbonyl, C6-C1 (raryl-CrCV alkoxycarbonyl, Q-CV alkylcarbonyl, C6-C1 (rarylcarbonyl, C6-C1()-aryl-(VCV alkylcarbonyl, crc6-alkylcarboxy, c6-c10-arylcarboxy, crc6-alkylthiol, c6-c10- Aromatic® 15 thiol, crc6-alkylmercaptocarbonyl, c3-c8-cycloalkylcarbonylcarbonyl, c6-c1 (rarylcarbonylcarbonyl, CrC6-alkylindenylcarboxy, c6-c10-aryl Mercaptocarboxy, CVCV alkylsulfonyl, c6-c1()-arylsulfonyl, CVCV alkylthiothio, c6-c1 (raryloxythio), each of which is selectively Substituted one or more times: CrC6-alkyl, CVC6-alkoxy 20, c6-c1 (r aryloxy, CO 2 H, S03H, amine, crc6-alkylamino, di-Ci_C6-alkylamino , sulfhydryl, thiol, decyl, cyano, fluoro, chloro, bromo, iodo, CF3 or OCF3; 55 200932732 co2h ; so3H; amine; 5 selected from the group below Substituting one or more amine groups for the residue: crc6-alkyl, C6-C10-aryl, C6-C1()-aryl-CVCV alkyl, Ci-CV alkylcarbonyl, c6-c10-aryl a carbonyl group, a crc6-alkylsulfonyl group, and a c6-c1 (rarylsulfonyl group; a disubstituted amino group having the following chemical formula (II):

Γ~\Γ~\

(II) 10 其中0代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Ci-CV烷基，及其中化學式(II)中的亞曱基可選擇性地被crc6-烷基、氟代基或氯代基取代一或二次； conh2 ; so2nh2 ; 15 conh2或so2nh2，其中該胺基官能度被選自Ci-CV烷(II) 10 wherein 0 represents 0 or 1, and W represents oxygen, CH2 or NR6, and R6 is selected from hydrogen and Ci-CV alkyl, and wherein the fluorenyl group in the formula (II) is optionally crc6- Substituting an alkyl, fluoro or chloro group for one or two times; conh2; so2nh2; 15 conh2 or so2nh2, wherein the amine functionality is selected from Ci-CV alkane

基、C6-C1()-芳基或C6-C1()-芳基-Q-C6-烷基的殘基取代一次或多次，及其中在一種經二-CrCV烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；硫氫基； 20 羥基；琐基；氰基；氣石黃酿基， 56 200932732 5 ❹ 10 15 ❹ 20 選自氟代基、氯代基、漠代基或峨代基之鹵素； cf3 ; OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統’其選擇性地被下列各者取代一或多次：Ci_C6_ 院基、CrC6·垸氧基、COOH、S〇3H、胺基、硫氫基、羥基、硝基、氰基、氟代基、氯代基、溴代基、碘代基、 cf3 或〇cf3 ; 及其中R2至R4中之任二或多者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統； η與m為0 ;及 Y為苯基，其被下列各者取代一或多:欠：Ci_C6_烧基；苯基；CrC6-燒氧基；織；氟代基；氯代基；溴代基； cf3 ; ocf3 ;胺基；或選擇性地被Ci々烷基取代一或二次之CONH2其中該等選擇性的Ci_C6_院基殘基可結合而形成5或6員環；或其#立體異構物、藥學上可接受的鹽類或醋或前驅藥物。在第三個非常佳的實施例中，本發明係有關於具化學式(I)的一化合物：Substituting one or more residues of a C6-C1()-aryl or C6-C1()-aryl-Q-C6-alkyl group, and an amine function substituted with a di-CrCV alkyl group In the case of degree, the alkyl residue may be combined to form a 5 or 6 membered ring; sulfhydryl; 20 hydroxy; triazole; cyano; gas yellow wine, 56 200932732 5 ❹ 10 15 ❹ 20 selected from fluorine a halogen of a thiol, chloro, molybdenum or oxime group; cf3; OCF3; or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms' selectively Substituted one or more times: Ci_C6_ yard, CrC6·decyloxy, COOH, S〇3H, amine, sulfhydryl, hydroxy, nitro, cyano, fluoro, chloro, bromo, Iodyl, cf3 or 〇cf3; and any two or more of R2 to R4 thereof may be combined to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; η and m are 0; Is a phenyl group which is substituted by one or more of the following: owed: Ci_C6_alkyl; phenyl; CrC6-alkoxy; woven; fluoro; chloro; bromo; cf3; ocf3; Or alternatively by Ci Substituting one or two of CONH2 wherein the selective Ci_C6_felt residues can be combined to form a 5 or 6 membered ring; or its # stereoisomer, pharmaceutically acceptable salt or vinegar or prodrug . In a third very preferred embodiment, the invention relates to a compound of formula (I):

(I) 57 200932732 其中R1或R5為氫或氟； R3或R4中之一者為Q-CV烷氧基、C6-C10-芳氧基、 C6-C10-芳基-CrC8-统氧基、Ci-Ce-烧基叛基、C6-C10-芳基羧基、Q-CV烷基巯基羧基、CVCW芳基毓基缓基、 5 Ci-CV烧基氧硫基、cvCw芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次：CkCV烷基、Cl_C6_烷氧基、C6-C10-芳氧基、co2h、S03H、胺基、Q-CV炫基胺基、二-CrC；6·院基胺基、硫氫基、經基、硕基、氰基、氟代基、氣代基、溴代基、碘代基、CF3或OCF3 ; © 10 r3或R4中之另一者為胺基’其經選自下列群中的殘基取代一或多次：Q-CV烷基、C6-C10-芳基、c6_Cl〇_芳基 -CVCV烧基、CrC6-烧基幾基、C6-Ch)-芳基幾基、crC6- - 烧基靖酿基及C6-Ci〇-芳基績酿基；及R2為： 15 氫； CVCV烧基、C3-C8-環炫基、C6-C1(r芳基、C6-Cnr芳基 -CVC8-烧基、CrC6-院氧基、C6-C1(r芳氧基、C6-C1(r芳基〇 -CVCs-烷氧基、q-Cr烷氧基羰基、C6-C1(r芳氧基羰基、 C6-C1(r芳基-CVCV烷氧基羰基、CVCV烷基羰基、C6-C10-20 芳基羰基、C6-C1()-芳基-CrC8-烷基羰基、Q-CV烷基羧基、 C6-C1()-芳基羧基、q-Ce-烷基氫硫基、C6-C1(r芳基氫硫基、 CVCV烷基酼基羰基、C3-C8-環烷基毓基羰基、C6-C1()-芳基巯基羰基、CrC6-烷基巯基羧基、c6-C1()-芳基酼基羧基、 C]_C6-烧基績酿基、Cg-Cio-芳基績酿基、（^1-匚6-炫> 基氧硫 58 200932732 基、c6-c1(r芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次：q-CV烷基、CrC6-烷氧基、C6-C10-芳氧基、 C02H、S03H、胺基、CVCV烷基胺基、二-G-cv烧基胺基、硫氫基、羥基、硝基、氰基、氟代基、氣代基、溴代基、 5 碘代基、CF3或〇CF3 ; co2h ； so3H; 胺基；(I) 57 200932732 wherein R1 or R5 is hydrogen or fluorine; one of R3 or R4 is Q-CV alkoxy, C6-C10-aryloxy, C6-C10-aryl-CrC8-oxyl, Ci-Ce-alkyl group, C6-C10-arylcarboxy group, Q-CV alkylmercaptocarboxy group, CVCW arylsulfonyl group, 5 Ci-CV alkyloxythio group, cvCw aryloxythio group, Each of them is optionally substituted one or more times by: CkCV alkyl, Cl_C6-alkoxy, C6-C10-aryloxy, co2h, S03H, amine group, Q-CV sylamino group, two -CrC;6. Institute of amine, sulfhydryl, thiol, phenyl, cyano, fluoro, carbyl, bromo, iodo, CF3 or OCF3; © 10 r3 or R4 The other is an amine group which is substituted one or more times by a residue selected from the group consisting of Q-CV alkyl, C6-C10-aryl, c6_Cl〇-aryl-CVCV alkyl, CrC6-alkyl a few groups, a C6-Ch)-aryl group, a crC6--alkyl group and a C6-Ci〇-aryl base; and R2 is: 15 hydrogen; CVCV alkyl, C3-C8-cyclos , C6-C1 (raryl, C6-Cnr aryl-CVC8-alkyl, CrC6-homoyloxy, C6-C1 (r aryloxy, C6-C1 (r aryl 〇-CVCs-alkoxy, q-Cr alkoxycarbonyl , C6-C1 (r-aryloxycarbonyl, C6-C1 (r-aryl-CVCV alkoxycarbonyl, CVCV alkylcarbonyl, C6-C10-20 arylcarbonyl, C6-C1()-aryl-CrC8- Alkylcarbonyl, Q-CV alkylcarboxy, C6-C1()-arylcarboxy, q-Ce-alkylthiol, C6-C1 (rarylthiothio, CVCV alkylmercaptocarbonyl, C3 -C8-cycloalkylfluorenylcarbonyl, C6-C1()-aryldecylcarbonyl, CrC6-alkylindenylcarboxy, c6-C1()-aryldecylcarboxy, C]_C6-alkyl base, Cg-Cio-aryl base, (^1-匚6-Hyun) oxysulfide 58 200932732 base, c6-c1 (raryloxythio group, each of which is selectively substituted by each of the following Or multiple times: q-CV alkyl, CrC6-alkoxy, C6-C10-aryloxy, C02H, S03H, amine, CVCV alkylamine, bis-G-cv alkylamino, sulfhydryl , hydroxy, nitro, cyano, fluoro, carbyl, bromo, 5 iodo, CF3 or hydrazine CF3; co2h; so3H; amine group;

© 經選自下列群中的殘基取代一或多次之胺基·· CrCV 10 烷基、C6-C10-芳基、c6-c10-芳基-CVC6-烷基、CrQ-烷基系基、C6-Ci〇-芳基叛基、Ci-C6_炫基續酿基及C6_Ci〇-方基、績醯基；具下列化學式(II)之一種經二取代的胺基：- Amino group substituted by one or more residues selected from the following groups · CrCV 10 alkyl group, C6-C10-aryl group, c6-c10-aryl-CVC6-alkyl group, CrQ-alkyl group , C6-Ci〇-aryl base, Ci-C6_Hyun base and C6_Ci〇-square, benzyl; a disubstituted amino group of the following formula (II):

—N /飞^]0 (II) 15 〇其中0代表0或1，而W代表氧、CH2或NR6，R6係選自氫與CVCV烷基，及其中化學式(II)中的亞曱基可選擇性地被crc6-烷基、氟代基或氯代基取代一或二次； conh2 ; so2nh2 ; 20 CONH2或S02NH2，其中該胺基官能度被選自crc6-烷基、C6-C1(r芳基或C6-C1(r芳基-CkCV烷基的殘基取代一次或多次，及其中在一種經二-CrCV烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環； 59 200932732 硫氫基；羥基；硝基；氰基； 5 氟磺醯基；選自氟代基、氯代基、溴代基或碘代基之鹵素； cf3 ; OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜環 ίο 式環系統，其選擇性地被下列各者取代一或多次：cvc 烷基、cvc6-烷氧基、COOH、S03H '胺基、硫氫基、麵基、硝基、氰基、氟代基、氣代基、溴代基、碘代基、 cf3 或 ocf3 ; η與m為0 ;及 !5 Y為苯基，其被下列各者取代一或多次：CrC6-烷基；本基；CVC6-烧氧基；經基；氟代基；氣代基；漠代基； CF3 ; 〇CF3 ;胺基；或選擇性地被crc6-烷基取代一或二 0 次之CONH2，其中該等選擇性的crc6-烷基殘基可結合而形成5或6員環； 20 或其一種立體異構物、藥學上可接受的鹽類或酯或前驅藥物。在該三個較佳實施例中，Y更佳為苯基，其被下列各者取代一或多次：CVC6-烷基；苯基；crC6-烷氧基；羥基；氟代基；氣代基：溴代基；CF3 ; 〇CF3 ;胺基；或選 60 200932732 擇性地被CrCV院基取代一或二次之c〇nh2，其中該等選擇性的CrCV烧基殘基可結合而形成5或6員環。在該三個較佳實施例中，γ又更佳為苯基，其被羥基、氣代基、氣代基或漬代基取代一或二次。 5 ❹ 10 15 ❹ 20 在該三個較佳實施例中，γ又更佳為苯基，其在4_位置被氟代基或被氣代基取代、在2_與4_位置被氟代基取代、在2-與4-位置被氣代基取代或在4-位置被苯基取代。在關於化合物本身之本發明的所有部份中，下列均適用：在關於化合物本身之本發明的實施例中，排除下列具化學式(I)的化合物： ’、 ^ 5-十二烧基氧-3-(4-三氟甲氧基-苯基)3 4)呋一唑-2-酮； ’ 5-十六烷基氧-3-(4-三氟甲氧基-苯基)_3H、(l，3釣呋二唑-2-酮； 5-辛基氧-3·(4-三氟甲氧基.苯基)_3H_(1，3,4)、^m 5-十六烷基氧-3-(3-三氟甲氧基-苯基)_3H、(1，3 呋二唾-2-酮； 5_十六烷基氧_3_(4-(4-氣笨氧基)·苯基)^ (以斗)咬 .唑-2-嗣； ’ ’ 辛基軋-3-本基-3H-(l，3,4)-〇夫二〇坐_2-_ ; 5 辛基氧-3-(3-氟-本基)_3Η-(1，3,4)-〇夫二。皇_2、酮. 酮 5-十六烧基氧-3.(3-氣-苯基)_3Η_(1,34κ二嗓韻； 5-十六烷基氧-3-(3-苄氧基_苯基)_3H(1，3,4)、呋二唑 61 200932732 5 -十六烧基氧-3 -苯基-3Η-(1，3,4)-π夫二。坐-2-鋼， 5-十六烷基氧-3-(4-硝基-笨基)-3Η-(1，3,4)-呋二唑-2-酮； 5-十六烷基氧-3-(4-甲氧基-苯基)-3Η-(1,3,4)-呋二唑-2-酮； 5-十六烷基氧-3-(4-f氧基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 5 5-癸基氧-3-(4-三氟曱氧基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 5-十一烷基氧-3-(4-三氟曱氧基-苯基)-3Η-(1,3,4)-呋二唑-2-酮； 5-十四烷基氧-3-(4-三氟曱氧基·苯基)-3Η-(1,3,4)-呋二唑-2-酮； © 1〇 5-十三烷基氧-3-(4-三氟甲氧基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 5-(2-(2-己基氧-乙氧基)-乙氧基)-3-(4-三氟甲氧基-苯 - 基)-3Η-(1，3,4)-呋二唑-2-酮； 5-((Ζ)-十八碳-9-烯基氧)-3-(4-三氟甲氧基-苯基)-3Η-15 (1，3,4)-π夫二0坐-2-酮；5-(十二烧基氧-乙氧基)_3-(4-二氟甲乳基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 5-(2-(4-氟苯基）-乙氧基）-3-(4-三氟曱氧基-苯 ® 基)-3Η-(1，3,4)-呋二唑-2-酮； 5-((3ss-膽甾烷-3-基）-氧）-3-(4-三氟甲氧基-苯 20 基)-3Η-(1，3,4)-呋二唑-2-酮； 5-(2- 丁氧基-乙氧基）-3-(4-三氟甲氧基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 5-(7-苯基-庚基氧）-3-(4-三氟曱氧基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 62 200932732 ^(―十二烷基氧-乙氧基）-3-(4-三氟甲氧基_苯基)-如(1，3,4)-吱二唾_2_嗣； (2 (1-萘氧基）_乙氧基）3 (4三氟甲氧基-本基）3Η-(ΐ，3,4)_β夫二唾_2__ ; 5 5~(4-辛基苯氧基）-3-(4-三氟甲氧基-苯基）3Η-(1，3,4)·吱二唾_2_酮； 5-(3_苯氧基_笨氧基）3_(4三氟甲氧基-苯基）犯-(1，3,4)-吱二唾_2_酮； 5-(十二烧基氧)_3♦三氟甲氧基苯基)務(1，3,4)_，夫 10 — °坐-2 -酮； 5 (十—烷基氧)_3'(3，4-二氣-苯基)_3Η-(1,3,4)，夫二唑 -2-酮； 5_(十二烷基氧)-3-(3，5-二氣_苯基)_3Η_(ι，3,4)-吹二唑 -2-酮； 15 十二烷基氧)-3-(3-甲氧基_苯基)_3Η_(1，3,4)-吱二唑 -2-酮； 5-(十二烷基氧)_3_(4_甲氧基·苯基) 3η (ι，3 4)，夫二唑 2-酿I 〇在有關於化合物本身之本發明的實施例中，當„!為0及η 20 為0時，Υ並非代表CrC4-烷基。而且，當m為0、η為〇及γ為一個選擇性地經取代的苯基環時，R2或R4並非代表取代基C(=a)-N(B)-S02-NR6R7，其中A代表氧或硫，B代表氫、氰基、Cl_C6_烷基、CrCV 烧氧基-炫基、CVC7-環烧基、C3-C6-烯烴基、C3-C6-炔基或 63 200932732 5 選擇性地被取代的苄基衍生物，及R6與R7係彼此獨立地代表氬或一有機殘基或一起代表一個有機環狀結構；當Y代表未經取代的苯基時，R1至R5彼此獨立地並非代表氫、氟代基、溴代基、氣代基、碘代基或一烷基游離基；R2或R4並非代表一種吡唑-3-基-衍生物；及經R1至R5取代的苯基環及 Y並非代表下列組合：經R1至R3取代的苯基環 Y 2-氣笨基 4-氣苯基 2,3-二甲基苯基 4-氣苯基 2,4-二氣苯基 4-氣苯基 2-氣-3-曱基苯基 4-氣苯基 2,5-二氟苯基 4-甲基苯基 2-曱氧基-4-氯苯基 4-氣苯基 2-氣苯基 _ 4-甲基苯基 2,6-二氣苯基 __ 4-乳苯基 2-(二氟甲基氫硫基）苯基苯基 2,3,4-二曱基苯基 4-氣苯基 2,5-二氟苯基 '~ 4-溴苯基 2,4-二甲基苯基 ~~' 4-氣苯基 4-氣苯基 4-氣苯基 3-氣苯基 '~~ 4-氣苯基 4->臭笨基 2-氣 ——'-- 4-氣苯基 4-溴苯基 2,5-一氣本基氣苯基 4-氣本基 4-溴苯基 3,5-—子基未基 4-氣苯基 4-二氟曱氧基苯基—N /飞^]0 (II) 15 〇 where 0 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and CVCV alkyl, and the fluorenyl group in the formula (II) Optionally substituted by a crc6-alkyl, fluoro or chloro group for one or two times; conh2; so2nh2; 20 CONH2 or S02NH2, wherein the amine functionality is selected from the group consisting of crc6-alkyl, C6-C1 (r The aryl or C6-C1 (raryl-CkCV alkyl residue may be substituted one or more times, and in the case of a di-CrCV alkyl substituted amine functionality, the alkyl residue may be combined And forming a 5 or 6 membered ring; 59 200932732 sulfhydryl; hydroxy; nitro; cyano; 5 fluorosulfonyl; halogen selected from fluoro, chloro, bromo or iodo; cf3; OCF3; or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, which is optionally substituted one or more times by: cvc alkyl, cvc6-alkoxy, COOH , S03H 'amino group, sulfhydryl group, surface group, nitro group, cyano group, fluoro group, gas group, bromo group, iodo group, cf3 or ocf3; η and m are 0; and !5 Y is Phenyl group, which is used by Substituted one or more times: CrC6-alkyl; this group; CVC6-alkoxy; transradical; fluoro group; gas group; molybdenum; CF3; 〇CF3; amine group; or alternatively by crc6- Alkyl substituted one or two times of CONH2, wherein the selective crc6-alkyl residues may combine to form a 5 or 6 membered ring; 20 or a stereoisomer thereof, a pharmaceutically acceptable salt or Ester or prodrug. In the three preferred embodiments, Y is more preferably a phenyl group which is substituted one or more times by: CVC6-alkyl; phenyl; crC6-alkoxy; hydroxy; fluoro Substituent; gas group: bromo group; CF3; 〇CF3; amine group; or 60 selected 200932732 alternatively substituted by CrCV, the first or second c〇nh2, wherein the selective CrCV burnt residue The groups may be combined to form a 5 or 6 membered ring. In the three preferred embodiments, gamma is more preferably a phenyl group which is substituted one or two times by a hydroxyl group, an oxyl group, a gas group or a germinating group. 5 ❹ 10 15 ❹ 20 In the three preferred embodiments, γ is more preferably a phenyl group which is substituted by a fluoro group or a gas group at the 4 position and is fluorinated at the 2 and 4 positions. Substituted, in 2-and The 4-position is substituted by a gas group or by a phenyl group at the 4-position. In all parts of the invention relating to the compound itself, the following applies: In the examples of the invention relating to the compound itself, the following are excluded Compound of formula (I): ', ^ 5-dodecyloxy-3-(4-trifluoromethoxy-phenyl)3 4)furazol-2-one; ' 5-hexadecyl Oxy-3-(4-trifluoromethoxy-phenyl)_3H, (l,3 furazolid-2-one; 5-octyloxy-3.(4-trifluoromethoxy.phenyl) )_3H_(1,3,4), ^m 5-hexadecyloxy-3-(3-trifluoromethoxy-phenyl)_3H, (1,3 furadipyre-2-one; 5_ Hexadecyloxy_3_(4-(4-gasooxy)·phenyl)^ (to the bucket) bite. Zyridin-2-indole; ' ' octyl-rolled 3-bens-3H-(l , 3, 4) - cowardly sitting 2 - 2; 5 octyloxy-3-(3-fluoro-benyl)_3Η-(1,3,4)-coward II.皇-2, ketone. Ketone 5-hexadecyloxy-3.(3-Gas-phenyl)_3Η_(1,34κ二嗓韵; 5-hexadecyloxy-3-(3-benzyloxy) _phenyl)_3H(1,3,4), furadiazole 61 200932732 5 -hexadecyloxy-3 -phenyl-3 fluorene-(1,3,4)-π-f. , 5-hexadecyloxy-3-(4-nitro-phenyl)-3Η-(1,3,4)-furadiazol-2-one; 5-hexadecyloxy-3-( 4-methoxy-phenyl)-3Η-(1,3,4)-furadiazol-2-one; 5-hexadecyloxy-3-(4-foxy-phenyl)-3Η -(1,3,4)-furadiazol-2-one; 5 5-mercaptooxy-3-(4-trifluoromethoxy-phenyl)-3Η-(1,3,4)-fur Dioxazol-2-one; 5-undecyloxy-3-(4-trifluorodecyloxy-phenyl)-3Η-(1,3,4)-furadiazole-2-one; 5- Tetradecyloxy-3-(4-trifluorodecyloxyphenyl)-3indole-(1,3,4)-furadiazol-2-one; © 1〇5-tridecyloxy- 3-(4-Trifluoromethoxy-phenyl)-3Η-(1,3,4)-furadiazol-2-one; 5-(2-(2-hexyloxy-ethoxy)-B Oxy)-3-(4-trifluoromethoxy-phenyl-yl)-3Η-(1,3,4)-furadiazol-2-one; 5-((Ζ)-octadeca-9 -alkenyloxy)-3-(4-trifluoromethoxy-phenyl)-3Η-15 (1,3,4)-π-fuxo-2-one; 5-(12-alkyloxy) -ethoxy)_3-(4- Fluoromethyl-phenyl)-3Η-(1,3,4)-furadiazol-2-one; 5-(2-(4-fluorophenyl)-ethoxy)-3-(4- Trifluoromethoxy-phenyl®)-3Η-(1,3,4)-furadiazol-2-one; 5-((3ss-cholest-3-yl)-oxy)-3-( 4-trifluoromethoxy-phenyl 20 yl)-3 Η-(1,3,4)-furadiazol-2-one; 5-(2-butoxy-ethoxy)-3-(4- Trifluoromethoxy-phenyl)-3Η-(1,3,4)-furadiazol-2-one; 5-(7-phenyl-heptyloxy)-3-(4-trifluoroantimony) -phenyl)-3Η-(1,3,4)-furadiazol-2-one; 62 200932732 ^(-dodecyloxy-ethoxy)-3-(4-trifluoromethoxy _Phenyl)--(1,3,4)-oxime-disc_2_嗣; (2 (1-naphthyloxy)-ethoxy)3 (4trifluoromethoxy-benyl) 3Η- (ΐ,3,4)_β夫二唾_2__ ; 5 5~(4-octylphenoxy)-3-(4-trifluoromethoxy-phenyl)3Η-(1,3,4) ·吱二唾_2_ ketone; 5-(3-phenoxy-phenyloxy)3_(4trifluoromethoxy-phenyl)--(1,3,4)-吱二唾_2_ Ketone; 5-(dodecyloxy)_3♦trifluoromethoxyphenyl)(1,3,4)_,f 10 — ° sit-2-ketone; 5 (deca-alkyloxy)_3 '(3,4-di-phenyl-phenyl)_3Η-(1,3,4), oxadiazol-2-one; 5_(dodecane Oxy)-3-(3,5-diqi_phenyl)_3Η_(ι,3,4)-thiadiazol-2-one; 15 dodecyloxy)-3-(3-methoxy- Phenyl)_3Η_(1,3,4)-oxadiazol-2-one; 5-(dodecyloxy)_3_(4-methoxyphenyl) 3η (ι,3 4), Fuji Iridium 2- Brewing I In the examples of the invention relating to the compound itself, when „! is 0 and η 20 is 0, Υ does not represent CrC4-alkyl. Moreover, when m is 0, η is 〇, and γ is a selectively substituted phenyl ring, R2 or R4 does not represent a substituent C(=a)-N(B)-S02-NR6R7, wherein A represents Oxygen or sulfur, B represents hydrogen, cyano, Cl_C6_alkyl, CrCV alkoxy-andyl, CVC7-cycloalkyl, C3-C6-alkenyl, C3-C6-alkynyl or 63 200932732 5 optionally a substituted benzyl derivative, and R6 and R7 independently of each other represent argon or an organic residue or together represent an organic cyclic structure; when Y represents an unsubstituted phenyl group, R1 to R5 are independently of each other Represents hydrogen, fluoro, bromo, carbyl, iodo or monoalkyl radical; R2 or R4 does not represent a pyrazol-3-yl-derivative; and phenyl substituted with R1 to R5 Ring and Y are not representative of the following combinations: Phenyl ring Y 2-cyclophenyl 4-phenylphenyl 2,3-dimethylphenyl 4-phenylphenyl 2,4-diphenyl substituted by R1 to R3 4-oxophenyl 2-ox-3-mercaptophenyl 4-phenylphenyl 2,5-difluorophenyl 4-methylphenyl 2-decyloxy-4-chlorophenyl 4-phenylphenyl 2-Phenylphenyl-4-methylphenyl 2,6-diphenylphenyl__ 4-lactylphenyl 2-(difluoromethylhydrogen sulfide Phenylphenyl 2,3,4-didecylphenyl 4-phenylphenyl 2,5-difluorophenyl '~ 4-bromophenyl 2,4-dimethylphenyl~~' 4- Phenylphenyl 4-phenylphenyl 4-phenylphenyl 3-phenylphenyl '~~ 4-phenylphenyl 4-> stinky 2- 2 - 4-phenylphenyl 4-bromobenzene Base 2,5-one gas, base gas, phenyl 4-carboyl, 4-bromophenyl 3,5--ylidyl, 4-phenylphenyl 4-difluorodecyloxyphenyl

而且田m為1、ι^(^γ為一個選擇性地經取代的笨基環時，γ並非代表未經取代的苯基，若r1、RW代表氣， 64 200932732 5 10 15 ❹ 20 R4代表氫、三氟甲氧基、三氟丁氧基、3,3,5,5-四甲基環己氧基、节氧基、苯氧基、苯基、2_二甲基胺基乙氧基或3_ 甲基苯氧基-曱基，及R3代表氫、三氟甲氧基、三氟丁氧基、 3,3,5,5-四甲基環己氧基、苯氧基、4氯苯氧基、環己基、苯基、嗎啉磺醯基、3,3 5_三甲基環己基胺基磺醯基、2,2,6,6_ 四甲基哌啶-4-基胺基磺醯基、2_(二異丙基胺基乙基)胺基磺醯基、4-曱基哌嗪―:^基—磺醯基、3,3_二甲基哌啶羰基或3,5_ 二氯苯氧基、2-二甲基胺基乙氧基或3_甲基苯氧基_曱基。而且’當m為1、n為〇及R3為三氟甲氧基，γ並非代表未經取代的苯基。在有關於化合物本身之本發明的一些任擇實施例中， R2至R5並非代表2-氧代-吡咯烷_；[_基、2,5_二曱基吡咯_丨_基或藉由一個非芳族氮與苯基環連接之一取代基，當n為〇與111 為0及當Υ代表q-C6-烷基、C3_C9_環烷基時，其中該二基選擇性地被苯基、CVCV烷基氧、硫-Q-CV烷基、氮(crC4-烷基h取代一或多次，及其中苯基選擇性地被鹵素、Ci_C4_ 烷基、CrCV烷基氧、硝基或Cf3取代一或多次。在有關於化合物本身之本發明的一些任擇實施例中，在η代表0及m代表〇之情況下，“或“並非代表一個選自鹵素的取代基，特別是氟、氣、N02、CH3、〇CH3或CF3或CN，當取代基R1至R5之其他者中的至少一者代表一個選自鹵素的取代基，特別是氟、氣、溴、CH3、〇CH3、N02、CN，及當Y所代表的本基被氟、氯、溴、CH3、0CH3、N〇2或CN 取代時。 65 200932732 在有關於化合物本身之本發明的一些任擇實施例中，在η代表0及m代表〇之情況下，γ並非代表被苯氧基或 C6-Cir烧基取代之苯基。在有關於化合物本身之本發明的一些任擇實施例中， 5在n代表0及"1代表1之情況下，Y並非代表未經取代的苯基。在有關於化合物本身之本發明的再任擇實施例中，在瓜為0及n為0之情況下，當R1至尺5代表_個氫或鹵素#H 個甲基游離基時，Y並非代表苯基或低級院基游離基。在有關於化合物本身之本發明的一些任擇實施例中， 10 r2至r5並非代表氫、鹵素、硝基、CrC4烷基、CrC9烷基氧、二氟甲基、三氟甲氧基4C6_Cl0_芳基基氧、c6_Ci〇芳基氧、CVCh)芳基、C3-C8環烷基或〇-C3-C8-環烷基，當η 為0與m為0 ’及當Υ代表被C4_C2〇烷氧基、C6_Ci〇芳基、C6_Ci〇芳基氧或CVCu-烷氧基-C2-C4-烷氧基取代之c7-C22烷基、 15 C2_C4烷基及代表Q-C2◦烯烴基、3β-膽留烷-3-基或代表經苯氧基或eve!2-烧基取代之苯基。在有關於化合物本身之本發明的又任擇實施例中，所有該等化合物可被(^-(:9烷基、 C1-C9烷基氧、齒素取代一或多次；及在芳基的情況下，被三氟甲基取代；及在環烷基的情況下，被crc4烷基或c6-c1() 20 芳基取代；及在烷基的情況下，被羥基、二-Ci-C*烷基胺基及氟代基取代。在有關於化合物本身之本發明的再任擇實施例中，在m 為0及η為0之情況下，Y並非代表被下列各者取代之笨基：具有1至4個碳原子的烷基；具有1至4個碳原子的烷氧基； 200932732 5 ❹ 10 15 20 具有1至4個碳原子的烷基硫代基；具有1至4個碳原子與具有1至5個鹵素原子的鹵代烷基，其中該等鹵素原子可相同或不同；具有1至4個碳原子與具有1至5個鹵素原子的南代烧氧基，其中該等鹵素原子可相同或不同；或具有〗至4個碳原子與具有1至5個画素原子的鹵代烷基硫代基，其中該等鹵素原子可相同或不同；具有1或2個破原子的亞烧二氧基，具有1或2個碳原子與1至4個鹵素原子之經鹵素取代的亞烷二氧基，其中該等齒素原子可相同或不同；氰基；硝基；具有2至4個碳原子的烷基羰基；具有2至4個碳原子的淀氧羰基；具有1至4個碳原子的烷基磺醯基；具有6或1〇個芳基碳原子的芳基磺醯基；苯基、萘基、苯氧基、萘氧基、苯硫基或萘硫基，當R1或R5代表鹵素時；具有1至4個礙原子的烷基；具有1至4個碳原子的烷氧基；具有1至4個碳原子的烷基硫代基；具有1至4個碳原子與具有1至5個幽素原子的鹵代烧基，其中該等鹵素原子可相同或不同；具有1至 4個碳原子與具有1至5個鹵素原子的鹵代烷氧基，其中該等卣素原子可相同或不同；或具有1至4個碳原子與具有1至5 個鹵素原子的鹵代烷基硫代基，其中該等鹵素原子可相同或不同；及當R1至R5之其他者中的一或多者代表氫時：具有1至4個碳原子的烧基；具有1至4個碳原子的统氧基；具有1至4個破原子的垸基硫代基；具有1至4個碳原子與具有1 至5個鹵素原子的鹵代烷基，其中該等鹵素原子可相同或不同；具有1至4個碳原子與具有1至5個鹵素原子的鹵代烷氧基，其中該等鹵素原子可相同或不同；或具有1至4個碳原 67 200932732 子與具有1至5個鹵素原子的鹵代烷基硫代基，其中該等鹵素原子可相同或不同；具有1或2個碳原子的亞烷二氧基；具有1或2個碳原子與1至4個鹵素原子之經鹵素取代的亞烷二氧基，其中該等鹵素原子可相同或不同；鹵素；氰基； 5 硝基；胺基；每個烷基基團具有1至4個碳原子之單烷基與二烧基胺基；具有2至4個碳原子的烷基羰基；具有2至4個碳原子的烷氧羰基；具有1至4個碳原子的烷基磺醯基；具有6或10個芳基碳原子的芳基磺醯基；苯基、萘基、笨氧基、萘氧i基、苯硫基或萘疏基。 10 在有關於化合物本身之本發明的再任擇實施例中，在n 代表0及m代表0之情況下，Ri或r5並非代表一個選自鹵素的取代基，特別是氟、氣、N〇2、CH3、〇CH3或CF3或CN ,當取代基R1至R5之其他者中的至少一者代表一個選自鹵素的取代基，特別是氟、氣、漠,、CH3、〇CH3、N〇2、CN，及 15當Y代表被氟、氣、溴、CHS、OCH3、N02*CN取代之苯基時。在有關於化合物本身之本發明的—些任擇實施例中，當Rl、R2及R5代表氫或當R1、R4及R5代表氫，及當m為1及n 為0時，Y並非代表選擇性地被苯基取代一或多次之crc6- 20烷基或C3_C9-環烧基，該苯基進而可被齒素、Ci_C4_烧基、 CVCV烧基氧、硝*基、Ci?3取代—或多次；或被〇 Ci_c4貌基、S-CrCV烷基、N(CrC4_烷基)2取代一或多次。在有關於化合物本身之本發明的—些任擇實施例中，當R1或R5代表氫與及當為辦，γ並非代表選擇性 200932732 地被苯基取代一或多次之crc6-烷基或c3-c9-環烷基，該苯基進而可被鹵素、Q-C4-烷基、crc4-烷基氧、硝基、cf3 取代一或多次；或被0-Q-C4-烷基、S-CVC4-烷基，I^Ci-Cr 烷基)2取代一或多次。 5 在另一方面，本發明亦係有關於使用具下列結構式(III) 之一藥效基團：Moreover, when m is 1, ι^ (^γ is a selectively substituted stupid ring, γ does not represent an unsubstituted phenyl group, if r1, RW represents gas, 64 200932732 5 10 15 ❹ 20 R4 represents Hydrogen, trifluoromethoxy, trifluorobutoxy, 3,3,5,5-tetramethylcyclohexyloxy, oxy, phenoxy, phenyl, 2-dimethylamino ethoxy Or 3-methylphenoxy-indenyl, and R3 represents hydrogen, trifluoromethoxy, trifluorobutoxy, 3,3,5,5-tetramethylcyclohexyloxy, phenoxy, 4 Chlorophenoxy, cyclohexyl, phenyl, morpholinsulfonyl, 3,3 5 -trimethylcyclohexylaminosulfonyl, 2,2,6,6-tetramethylpiperidin-4-ylamine Sulfosyl, 2-(diisopropylaminoethyl)aminosulfonyl, 4-mercaptopiperazine-:yl-sulfonyl, 3,3-dimethylpiperidinylcarbonyl or 3, 5-dichlorophenoxy, 2-dimethylaminoethoxy or 3-methylphenoxy-fluorenyl. And 'when m is 1, n is fluorene and R3 is trifluoromethoxy, γ is not Representative of unsubstituted phenyl. In some optional embodiments of the invention relating to the compound itself, R2 to R5 are not representative of 2-oxo-pyrrolidine _; [-based, 2,5-dimercaptopyridinium a substituent attached to the phenyl ring by a non-aromatic nitrogen, wherein n is 〇 and 111 is 0 and when Υ represents q-C6-alkyl, C3_C9_cycloalkyl, The diyl group is optionally substituted one or more times with phenyl, CVCV alkyl oxygen, sulfur-Q-CV alkyl, nitrogen (crC4-alkyl h, and wherein the phenyl group is selectively halogen, Ci_C4_alkyl, CrCV Alkyloxy, nitro or Cf3 is substituted one or more times. In some optional embodiments of the invention relating to the compound itself, where η represents 0 and m represents oxime, "or" does not represent a a substituent of a halogen, particularly fluorine, gas, N02, CH3, 〇CH3 or CF3 or CN, when at least one of the other substituents R1 to R5 represents a substituent selected from a halogen, particularly fluorine or gas , bromine, CH3, hydrazine CH3, N02, CN, and when the group represented by Y is substituted by fluorine, chlorine, bromine, CH3, 0CH3, N〇2 or CN. 65 200932732 In the present invention relating to the compound itself In some optional embodiments, where η represents 0 and m represents 〇, γ does not represent a phenyl group substituted with a phenoxy group or a C6-Cir alkyl group. In some optional embodiments of the invention of the invention, 5 wherein n represents 0 and "1 represents 1, Y does not represent an unsubstituted phenyl group. Further embodiments of the invention relating to the compound itself In the case where the melon is 0 and n is 0, when R1 to 5 represent _ hydrogen or halogen #H methyl radical, Y does not represent a phenyl or a lower-grade free radical. In some optional embodiments of the invention of the invention, 10 r2 to r5 do not represent hydrogen, halogen, nitro, CrC4 alkyl, CrC9 alkyloxy, difluoromethyl, trifluoromethoxy 4C6_Cl0_aryl Oxygen, c6_Ci aryloxy, CVCh) aryl, C3-C8 cycloalkyl or 〇-C3-C8-cycloalkyl, when η is 0 and m is 0' and when Υ represents C4_C2 decyloxy, C6_Ci aryl, C6_Ci aryloxy or CVCu-alkoxy-C2-C4-alkoxy substituted c7-C22 alkyl, 15 C2_C4 alkyl and represents Q-C2 decyl, 3β-cholane The -3-yl group represents a phenyl group substituted with a phenoxy group or an eve!2-alkyl group. In still another optional embodiment of the invention relating to the compound itself, all such compounds may be substituted one or more times by (^-alkyl, C1-C9 alkyloxy, dentate; and in aryl In the case of a trifluoromethyl group; and in the case of a cycloalkyl group, substituted by a crc4 alkyl group or a c6-c1() 20 aryl group; and in the case of an alkyl group, a hydroxy group, a di-Ci- C*alkylamino group and fluoro group substitution. In a further optional embodiment of the invention relating to the compound itself, in the case where m is 0 and η is 0, Y does not represent a stupid base which is replaced by An alkyl group having 1 to 4 carbon atoms; an alkoxy group having 1 to 4 carbon atoms; 200932732 5 ❹ 10 15 20 an alkylthio group having 1 to 4 carbon atoms; having 1 to 4 carbons An atom and a haloalkyl group having 1 to 5 halogen atoms, wherein the halogen atoms may be the same or different; a halogenated alkoxy group having 1 to 4 carbon atoms and having 1 to 5 halogen atoms, wherein the halogen atoms Or the same or different; or a halogenated alkylthio group having from 4 to 4 carbon atoms and from 1 to 5 pixel atoms, wherein the halogen atoms may be The same or different; a calcined dioxy group having 1 or 2 broken atoms, a halogen-substituted alkylenedioxy group having 1 or 2 carbon atoms and 1 to 4 halogen atoms, wherein the dentate atoms may be Identical or different; cyano; nitro; alkylcarbonyl having 2 to 4 carbon atoms; oxycarbonyl having 2 to 4 carbon atoms; alkylsulfonyl having 1 to 4 carbon atoms; Or an arylsulfonyl group of 1 aryl carbon atom; phenyl, naphthyl, phenoxy, naphthyloxy, phenylthio or naphthylthio, when R1 or R5 represents a halogen; having 1 to 4 An alkyl group which has an atom; an alkoxy group having 1 to 4 carbon atoms; an alkylthio group having 1 to 4 carbon atoms; a halogen having 1 to 4 carbon atoms and having 1 to 5 crypto atoms a calcining group, wherein the halogen atoms may be the same or different; having 1 to 4 carbon atoms and a haloalkoxy group having 1 to 5 halogen atoms, wherein the halogen atoms may be the same or different; or having 1 to 4 a carbon atom and a haloalkylthio group having 1 to 5 halogen atoms, wherein the halogen atoms may be the same or different; and when the other of R1 to R5 One or more of them represent hydrogen: a burnt group having 1 to 4 carbon atoms; a base having 1 to 4 carbon atoms; a mercaptothio group having 1 to 4 broken atoms; having 1 to 4 a carbon atom and a halogenated alkyl group having 1 to 5 halogen atoms, wherein the halogen atoms may be the same or different; a halogenated alkoxy group having 1 to 4 carbon atoms and having 1 to 5 halogen atoms, wherein the halogen atoms Or the same or different; or having 1 to 4 carbon atoms 67 200932732 and a haloalkylthio group having 1 to 5 halogen atoms, wherein the halogen atoms may be the same or different; a subunit having 1 or 2 carbon atoms Alkanedioxy; a halogen-substituted alkylenedioxy group having 1 or 2 carbon atoms and 1 to 4 halogen atoms, wherein the halogen atoms may be the same or different; halogen; cyano; 5 nitro; amine a monoalkyl group and a dialkylamino group having 1 to 4 carbon atoms per alkyl group; an alkylcarbonyl group having 2 to 4 carbon atoms; an alkoxycarbonyl group having 2 to 4 carbon atoms; An alkylsulfonyl group having 1 to 4 carbon atoms; an arylsulfonyl group having 6 or 10 aryl carbon atoms; benzene , Naphthyl, stupid group, a naphthyl group i oxo, mercapto phenylthio or naphthylthio. In a further optional embodiment of the invention relating to the compound itself, in the case where n represents 0 and m represents 0, Ri or r5 does not represent a substituent selected from halogen, in particular fluorine, gas, N〇2 , CH3, 〇CH3 or CF3 or CN, when at least one of the other substituents R1 to R5 represents a substituent selected from halogen, particularly fluorine, gas, desert, CH3, 〇CH3, N〇2 , CN, and 15 when Y represents a phenyl group substituted by fluorine, gas, bromine, CHS, OCH3, N02*CN. In some optional embodiments of the invention relating to the compound itself, when R1, R2 and R5 represent hydrogen or when R1, R4 and R5 represent hydrogen, and when m is 1 and n is 0, Y is not representative of choice Substituted one or more crc6-20 alkyl or C3_C9-cycloalkyl groups by a phenyl group, which may in turn be substituted by dentate, Ci_C4_alkyl, CVCV alkyloxy, nitro-based, Ci?3 One or more times; or one or more times substituted by Ci_c4, S-CrCV alkyl, N(CrC4_alkyl)2. In some optional embodiments of the invention relating to the compound itself, when R1 or R5 represents hydrogen and when, γ does not represent a selective 200932732 substituted by a phenyl group one or more crc6-alkyl groups or a c3-c9-cycloalkyl group which may in turn be substituted one or more times by halogen, Q-C4-alkyl, crc4-alkyloxy, nitro, cf3; or by 0-Q-C4-alkyl, S-CVC4-alkyl, I^Ci-Cr alkyl)2 is substituted one or more times. 5 In another aspect, the invention is also directed to the use of a pharmacophore having the following structural formula (III):

〇 (III) 以製備用於抑制FAAH的一化合物，及治療因脂肪酸 10 醯胺水解酶（FAAH)抑制作用而受到正面影響之一病症，特別是用於治療所提及的醫學適應症。在另一方面，本發明亦係有關於包含具下列結構式 (III)的一藥效基團之化合物：〇 (III) To prepare a compound for inhibiting FAAH, and to treat a condition which is positively affected by the inhibition of fatty acid 10 guanamine hydrolase (FAAH), particularly for the treatment of the mentioned medical indications. In another aspect, the invention is also directed to a compound comprising a pharmacophore having the formula (III):

〇 15 (III) 以用於抑制FAAH，及治療因脂肪酸醯胺水解酶 (FAAH)抑制作用而受到正面影響之一病症，特別是用於治療所提及的醫學適應症。在本申請案的内涵中，應瞭解“藥效基團”一詞，係指與 20 FAAH酵素的交互作用所必需之分子的分子子單元或子結構 69 200932732 或部份。應瞭解具化學式(in)的藥效基團 < 進’步被取代在另-方面，本發明亦係有關於用於製備如申5月專利範圍第1至17項及第24至79項中任一項的/化合物之一種方法’其中具化學式(Ι\Γ)的一化合物： 5〇 15 (III) is used to inhibit FAAH, and to treat a condition that is positively affected by the inhibition of fatty acid indoleamine hydrolase (FAAH), particularly for the treatment of the mentioned medical indications. In the context of this application, it is to be understood that the term "pharmacophore group" refers to a molecular subunit or substructure of a molecule necessary for interaction with 20 FAAH enzymes 69 200932732 or part. It should be understood that the pharmacophores of formula (in) are replaced by the other steps, and the invention is also related to the preparation of items 1 to 17 and 24 to 79 of the patent scope of May. A method of any of the compounds/compounds wherein a compound of the formula (Ι\Γ): 5

R1至R5係彼此獨立地代表：氮； 15R1 to R5 are independently of each other: nitrogen; 15

CVCV院基、c3-c8-環烷基、C6-C10-芳基、C6-C10-芳基 ~Ci-C8-烧基、Ci-C6_烧氧基、C6-Ci〇-芳氧基、C6-C1〇-芳基 <VC8_烷氧基、Crc6-烷氧基羰基、c6-c1()-芳氧基羰基、 C6-C1Q-芳基-CVCV烷氧基羰基、CVCV烷基羰基、C6-C1(r 芳基羰基、C6-C1(r芳基-CrC8-烷基羰基、CVC6-烷基竣基、 C6-Ci〇-芳基竣基、Ci-C6-烧基氮硫基、C6-Ci〇-芳基氫硫基、 CVCV烷基巯基羰基、Cs-CV環烷基髄基羰基、CVc1()-芳基頸基幾基、CVC6·烧基疏基缓基、CVCio-芳基疏基缓基^、 Ci_C6_烧基績酿基、C6-Ciq-芳基績酿基、Ci-C6_境基氧碎基、C6-ClQ-芳基氧硫基’其中各者選擇性地被下列各者| 代一次或多次：CVCV烷基、CrC6-烷氧基、基、 C〇2H、SO3H、胺基、Ci-C6_炫·基胺基、二-Ci-C6-燒基胺義硫氫基、羥基、靖基、氰基、氟代基、氣代基、填代基^、 70 20 200932732 碘代基、CF3或OCF3 ; co2h ; so3h ；胺基； 5 Ο 經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、C6-C1(r芳基、C6-C10-芳基-Q-CV烷基、crc6-烷基羰基、C6-C1Q-芳基羰基、CVC6-烷基磺醯基及c6-c1()-芳基磺醯基；具下列化學式(II)之一種經二取代的胺基：CVCV, C3-C8-cycloalkyl, C6-C10-aryl, C6-C10-aryl~Ci-C8-alkyl, Ci-C6_alkoxy, C6-Ci〇-aryloxy, C6-C1〇-aryl<VC8_alkoxy, Crc6-alkoxycarbonyl, c6-c1()-aryloxycarbonyl, C6-C1Q-aryl-CVCV alkoxycarbonyl, CVCV alkylcarbonyl , C6-C1 (r arylcarbonyl, C6-C1 (raryl-CrC8-alkylcarbonyl, CVC6-alkylindenyl, C6-Ci〇-arylindenyl, Ci-C6-alkylthio) , C6-Ci 〇-aryl thiol group, CVCV alkyl fluorenylcarbonyl, Cs-CV cycloalkyl fluorenylcarbonyl, CVc1 ()-aryl aryl aryl, CVC6 thiol thiol, CVCio- Aryl sulfhydryl slow base ^, Ci_C6_ sinter base, C6-Ciq-aryl base, Ci-C6_ basal oxygen base, C6-ClQ-aryl oxythio group One or more times: CVCV alkyl, CrC6-alkoxy, yl, C〇2H, SO3H, amine, Ci-C6_Hyun-ylamino, di-Ci-C6- Anthracenyl sulfhydryl, hydroxy, jing, cyano, fluoro, hydroxy, substituted, ^ 70 20 200932732 iodo, CF3 or OCF3; co2h; so3h; amine; 5 Ο selected Residues from the following groups One or more amino groups: crc6-alkyl, C6-C1 (r aryl, C6-C10-aryl-Q-CV alkyl, crc6-alkylcarbonyl, C6-C1Q-arylcarbonyl, CVC6 -alkylsulfonyl and c6-c1()-arylsulfonyl; a disubstituted amino group of the following formula (II):

10 其中0代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-C6-烷基，及其中化學式(II)中的亞甲基可選擇性地被(^-(:6-烷基、氟代基或氯代基取代一或二次； CONH2 ; 15 Ο so2NH2; CONH2或S02NH2，其中該胺基官能度被選自crc6-烷基、C6-C1()-芳基或C6-C1(r芳基-CVC6-烷基的殘基取代一或二次，及其中在一種經二-CrC6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；硫氫基；羥基；梢基；氰基； 71 200932732 氣績酿基，選自氟代基、氣代基、溴代基或碘代基之i素； cf3 ; OCF3 ;或 5 一種由至多10個原子組成之飽和、不飽和或芳族雜環10 wherein 0 represents 0 or 1, and W represents oxygen, CH2 or NR6, and R6 is selected from hydrogen and Q-C6-alkyl, and wherein the methylene group in the formula (II) is selectively (^-( : 6-alkyl, fluoro or chloro group substituted one or two times; CONH2; 15 Ο so2NH2; CONH2 or S02NH2, wherein the amine functionality is selected from the group consisting of crc6-alkyl, C6-C1()-aryl Or a C6-C1 (raryl-CVC6-alkyl residue substituted one or two times, and wherein in the case of a di-CrC6-alkyl substituted amine functionality, the alkyl residue may be Combines to form a 5- or 6-membered ring; sulfhydryl; hydroxy; aryl; cyano; 71 200932732 gas-based, selected from fluoro, a gas, bromo or iodo; cf3 ; OCF3 ; or 5 a saturated, unsaturated or aromatic heterocyclic ring consisting of up to 10 atoms

式環系統，其選擇性地被下列各者取代一或多次：crc6-烷基、CrCV烷氧基、COOH、S03H、胺基、硫氫基、羥基、罐基、氰基、氟代基、氣代基、>臭代基、峨代基、 CF3 或 OCF3 ; 10 及其中R1至R5中之任二或多者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統； m代表0、1、2、3、4、5或6; Y代表： a)氫； 15 b)Ci_Ci8_烧基、早元不飽和或多元不飽和C2_Ci8_亞烧a ring system which is optionally substituted one or more times by: crc6-alkyl, CrCV alkoxy, COOH, S03H, amine, sulfhydryl, hydroxy, canister, cyano, fluoro , a gas radical, > odoro, oxime, CF3 or OCF3; 10 and any two or more of R1 to R5 thereof may combine to form a fused saturated, unsaturated or aromatic homocyclic or hetero Ring system; m stands for 0, 1, 2, 3, 4, 5 or 6; Y stands for: a) hydrogen; 15 b) Ci_Ci8_alkyl, early unsaturated or polyunsaturated C2_Ci8_

基、C3-C8-環烧基、C6_Ci〇-芳基、C6-Ci〇-芳基-Ci_C8-烧基、Ci_ C6_烧氧基、C6-Ci〇-芳氧基、C6-Ci〇-芳基-Ci_C8-烧氧基、Q-CV烷氧基羰基、c6-c1()-芳氧基羰基、c6-c10-芳基-Cr C8-烷氧基羰基、Ci-Ce-烷基羰基、C6-C1(r芳基羰 20 基、C6-C1(r芳基-CrC8-烷基羰基、CrC6-烷基羧基、芳基叛基、Ci_C6_烧基氮硫基、C6-Ci〇_方基風硫基、Ci-CV烷基巯基羰基、c3-c8-環烷基毓基羰基、 C6-C1(r芳基酼基羰基、CVC6-烷基毓基羧基、c6-c1()-芳基酼基羧基、c!- c6-烷基磺醯基、c6-c1()-芳基磺醯基、 72 200932732 crc6-烷基氧硫基、C6-C10-芳基氧硫基或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其中各者選擇性地被下列各者取代一次或多次： bl)Ci-C6-烧基、C3-C8-壤烧基、C6-Ci〇-芳基、 5 C6-C10-芳基-CVCV烷基、CVQ-烷氧基、C6-C10-芳氧基、c6-c1()-芳基-CrQ-烷氧基、Ci-CV烷氧基羰基、 c6-c1()-芳氧基羰基、c6-c1()-芳基-Q-CV烷氧基羰基、 CVC6-烷基羰基、c6-c1(r芳基羰基、c6-c10-芳基-crc8-〇烷基羰基、CkCV烷基羧基、c6-c1()-芳基羧基、crc6-烷 10 基鼠硫基、C6-Ci〇-方基鼠硫基、Ci-Cg-烧基魏基叛基、 ' c3-c8-環烷基酼基羰基、c6-c1(r芳基酼基羰基、crc6-烷 - 基酼基羧基、C6-C1G-芳基巯基羧基、CkCV烷基磺醯基、C6-C1(r芳基磺醯基、Q-CV烷基氧硫基、c6-c10-芳基氧硫基，其中各者選擇性地被下列各者取代一次或多 15 次：CVC6-烷基；CVC6-烷氧基；CONH2 ; S02NH2 ;其中該胺基官能度被CVCV烷基取代一次或二次之conh2 ❿ 或S02NH2 ; S03H ; C02H ;胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、c6-c10-芳基、 c6-c1()-芳基-CrC6-烷基、CVCV烷基羰基、c6-c1(r芳基 20 幾基、Ci-Cg-烧基績酿基及C6-Ci〇-方基續酿基，硫氣基；羥基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；CF3 ;或OCF3 ; 其中bl)中的數個取代基可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統； 73 200932732 或被： b2)羥基；硫氫基；硝基；氰基；氟代基；氣代基； 10 溴代基；碘代基；cf3 ; co2h ; so3h ; 〇cf3 ; conh2 ; so2nh2 ; conh2*so2nh2，其中該胺基官能度被選自Ci-C6-烧基、C6-Ci〇-芳基或C6-C10-芳基-CrC6-烧基的殘基取代一或二次，及其中在一種經二-Ci-Ce-烧基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：Ci_C6_烧基、C6-Ci〇-芳基、C6-Ci〇-芳基 -Ci-Cg-烧基、Ci-C6-院基幾基、C6_Ci〇-芳基幾基、或具下列化學〇 crc6-烷基磺醯基及c6-c1(r芳基磺醯基式(II)之一種經二取代的胺基：, C3-C8-cycloalkyl, C6_Ci〇-aryl, C6-Ci〇-aryl-Ci_C8-alkyl, Ci_C6_alkoxy, C6-Ci〇-aryloxy, C6-Ci〇- aryl-Ci_C8-alkoxy, Q-CV alkoxycarbonyl, c6-c1()-aryloxycarbonyl, c6-c10-aryl-Cr C8-alkoxycarbonyl, Ci-Ce-alkylcarbonyl , C6-C1 (r-arylcarbonyl 20-base, C6-C1 (r-aryl-CrC8-alkylcarbonyl, CrC6-alkylcarboxy, aryl-rebase, Ci_C6-alkylthio group, C6-Ci〇_ Square thiol group, Ci-CV alkyl fluorenylcarbonyl, c3-c8-cycloalkylcarbonylcarbonyl, C6-C1 (r aryl fluorenylcarbonyl, CVC6-alkylmercaptocarboxyl, c6-c1()- Aryl fluorenylcarboxy, c!- c6-alkylsulfonyl, c6-c1()-arylsulfonyl, 72 200932732 crc6-alkyl oxythio, C6-C10-aryl oxythio or one A saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, each of which is optionally substituted one or more times by: bl) Ci-C6-alkyl, C3-C8- Alkyl, C6-Ci〇-aryl, 5 C6-C10-aryl-CVCV alkyl, CVQ-alkoxy, C6-C10-aryloxy, c6-c1()-aryl-CrQ-alkoxy Base, Ci-CV alkoxycarbonyl, c6-c1()-aryloxy Carbonyl, c6-c1()-aryl-Q-CV alkoxycarbonyl, CVC6-alkylcarbonyl, c6-c1 (rarylcarbonyl, c6-c10-aryl-crc8-decylcarbonyl, CkCV alkane Carboxyl group, c6-c1()-arylcarboxy group, crc6-alk 10 group murine thio group, C6-Ci〇-square thiol group, Ci-Cg-alkyl-based thiol group, 'c3-c8-ring Alkyl fluorenylcarbonyl, c6-c1 (r aryl fluorenylcarbonyl, crc6-alkyl- fluorenylcarboxy, C6-C1G-aryldecylcarboxy, CkCV alkylsulfonyl, C6-C1 (rarylsulfonate) Anthracenyl, Q-CV alkyl oxythio, c6-c10-aryl oxythio, each of which is optionally substituted one or more times by: CVC6-alkyl; CVC6-alkoxy; CONH2; S02NH2; wherein the amine functionality is replaced by a CVCV alkyl group once or twice conh2 ❿ or S02NH2; S03H; C02H; an amine group; one or more amine groups substituted with a residue selected from the group consisting of: Crc6-alkyl, c6-c10-aryl, c6-c1()-aryl-CrC6-alkyl, CVCV alkylcarbonyl, c6-c1 (raryl 20 decyl, Ci-Cg-alkyl base) And C6-Ci〇-square base, sulfur gas group; hydroxyl group; nitro group; cyano group; fluoro group; gas group; bromo group; iodo group; CF3; F3; wherein several substituents in bl) may combine to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; 73 200932732 or by: b2) hydroxy; sulfhydryl; nitro; cyano Fluoro group; gas group; 10 bromo group; iodo group; cf3; co2h; so3h; 〇cf3; conh2; so2nh2; conh2*so2nh2, wherein the amine functionality is selected from Ci-C6-alkyl Substituting one or two residues of a C6-Ci-aryl- or aryl-C6-C10-aryl-CrC6-alkyl group, and the amino group functionality substituted with a di-Ci-Ce-alkyl group The alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of Ci_C6_alkyl, C6-Ci〇-aryl , C6-Ci〇-aryl-Ci-Cg-alkyl, Ci-C6-homo-based, C6_Ci〇-aryl, or the following chemical 〇crc6-alkylsulfonyl and c6-c1 ( a disubstituted amide group of the formula (II):

〇 (II) 15〇 (II) 15

其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與CrCV烷基，及其中化學式(II)中的亞甲基可選擇性地被Q-C6-烷基、氟代基或氣代基取代一或二次；或被： b3)—種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次： CrC6-烷基；CrCV 烷氧基；COOH ; CONH2 ; S02NH2 ;其中該胺基官能度被crc6-烷基取代一次或二次之conh2或so2nh2 ; so3h ;胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、c6-c10-芳 74 20 200932732 基、c6- C10-芳基-CnCV烧基、Ci-CV院基羰基、c6-c1(r 芳基幾基、CrCV烧基績醯基及C6-C1(r芳基績醯基；硫氳基；經基；确基；氰基；氟代基；氯代基；溴代基；碘代基；CF3 ;或OCF3 ; 5 c)S〇3H ;胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6-烧基、C6-C1()-芳基、C6-C1(r芳基-CrC8-烧基、Ci-CV烧基幾基、C6-C1()-芳基幾基、crcv院基續醯基及 C6-C10-芳基確酿基；CONH2 ; so2nh2 ; conh2 戋 S〇2NH2 ’其中該胺基官能度被選自Cl_Ce_烷基、c6_Ci〇_$ 10 基或C6-Ci〇-^r基-C1-C4-烧基的殘基取代一次或二次，及其中在一種經二-CrC6_烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；硫氫基；羥基；硝基；氰基；氟磺醯基；選自氟代基、氣代基、溴代基或碘代基之鹵素；cf3 ;或〇cf3 ; 15 環化形成一種呋二唑酮環系統。形成呋二唑酮環系統的環化步驟，較佳藉由碳醯氯、羰基二咪唑或一種碳酸酯而達成。適宜的碳酸目旨特別SCVCV烧基碳酸酯。碳醯氯與羰基二咪唑係達成環化作用的最佳試劑。 20 在上述化學式(IV)中，較佳R1至R5彼此獨立地代表氯；經基；Q-CV院基、c6-C10-芳基、CVC6-烧氧基、c6_Ci〇芳氧基、C6-C10-芳基-CVCV烷氧基、Ci-CV烷基羧基、 c0-c1Q·芳基鲮基、Ci_C0_烷基磺醯基、C6_Ci〇芳基磺酿基，其中各者選擇性地被下列各者取代一或多次：C_C_ 75 200932732 烧基、Ci-CV烧氧基、選擇性地被crC6-烧基或c6-C10-芳基取代一或二次之conh2或so2nh2 ;胺基、crc4-烷基胺基、二-Ci_C4_烧基胺基、經基、氟代基、氣代基、溴代基、CF3或OCF3 ;胺基；經選自Cl-C6-烷基、C6-C〗0-芳基 5 的殘基取代一或多次之胺基；具下列化學式（II)之一種經二取代的胺基： —(/ ~"w ° (II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自 © 氫與G-C4-烧基’及其中化學式(II)中的亞甲基可選擇性地 10 被C1-C4-烧基、氟代基或氣代基取代一或二次；c〇nh2 ; S〇2NH2;其中該胺基官能度選擇性地被選自crc6-烧基或 C6_C10-芳基的殘基取代一次或多次之c〇NH2或so2nh2 ; 氟代基；氣代基；溴代基；cf3 ;或ocf3。在上述化學式(IV)中’更佳R1至R5中之一或多者代表氟 15 或氣。最佳R1或R5代表氟。更佳，在上述化學式(IV)中，R1至R5中之一或多者代表 ❹ 經基；C!-C6-烧氧基、c6-c10-芳氧基、c6-C10-芳基-CrC6-院氧基、CrC6-烧基it基、C6-C1()-芳基叛基、crC6-燒基橫醯基、C6-C1(r芳基績醯基，其中各者選擇性地被下列各 20 者取代一或多次：C1_C6_烷基、CrCV烷氧基、選擇性地被Wherein 〇 represents 0 or 1, and W represents oxygen, CH2 or NR6, R6 is selected from hydrogen and CrCV alkyl, and the methylene group in the formula (II) is optionally Q-C6-alkyl, fluorine Substituting a substituent or a gas radical for one or two times; or by: b3) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, optionally substituted by one or the following Multiple times: CrC6-alkyl; CrCV alkoxy; COOH; CONH2; S02NH2; wherein the amine functionality is replaced by crc6-alkyl one or two times conh2 or so2nh2; so3h; amine group; The residue in the group is substituted with one or more amine groups: crc6-alkyl, c6-c10-aryl 74 20 200932732, c6-C10-aryl-CnCV alkyl, Ci-CV, carbonyl, c6-c1 ( r aryl yl, CrCV, fluorenyl and C6-C1 (r aryl fluorenyl; thiol; thiol; decyl; cyano; fluoro; chloro; bromo; Alkyl; CF3; or OCF3; 5 c) S〇3H; an amine group; one or more amine groups substituted with a residue selected from the group consisting of CrC6-alkyl, C6-C1()-aryl, C6-C1 (r-aryl-CrC8-alkyl, Ci-CV alkyl, C6-C1()-aryl a cyclyl group, a Crc-C10-aryl group, and a C6-C10-aryl group; CONH2; so2nh2; conh2 戋S〇2NH2 ' wherein the amine functionality is selected from the group consisting of Cl_Ce_alkyl, c6_Ci〇_$ 10 or The C6-Ci〇-^r-C1-C4-alkyl residue is substituted once or twice, and in the case of a di-CrC6-alkyl substituted amine functionality, the alkyl residue May form a 5 or 6 membered ring; sulfhydryl; hydroxy; nitro; cyano; fluorosulfonyl; halogen selected from fluoro, carbyl, bromo or iodo; cf3; 〇cf3; 15 cyclization to form a furadiazolone ring system. The cyclization step to form the furadiazolone ring system is preferably achieved by carbonium chloride, carbonyldiimidazole or a carbonate. Particularly SCVCV alkyl carbonate. The best reagent for the cyclization of carbon ruthenium chloride and carbonyl diimidazole. 20 In the above formula (IV), preferably R1 to R5 represent chlorine independently of each other; via; Q-CV Affiliation, c6-C10-aryl, CVC6-alkoxy, c6_Ci aryloxy, C6-C10-aryl-CVCV alkoxy, Ci-CV alkylcarboxy, c0-c1Q.aryl fluorenyl, Ci_C0_alkyl Anthracenyl, C6_Ci arylsulfonyl, each of which is optionally substituted one or more times by: C_C_ 75 200932732 alkyl, Ci-CV alkoxy, optionally by crC6-alkyl or c6 -C10-aryl substituted one or two conh2 or so2nh2; amine group, crc4-alkylamino group, di-Ci_C4_alkylamino group, thiol group, fluoro group, carbyl group, bromo group, CF3 Or OCF3; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of Cl-C6-alkyl, C6-C 0-aryl 5; a disubstituted amine of the following formula (II) Base: —(/ ~"w ° (II) where 〇 represents 0 or 1, and W represents oxygen, CH2 or NR6, and R6 is selected from © hydrogen and G-C4-alkyl and its chemical formula (II) The methylene group may be optionally 10 replaced by a C1-C4-alkyl group, a fluoro group or a gas group for one or two times; c〇nh2; S〇2NH2; wherein the amine group functionality is selectively selected from The residue of crc6-alkyl or C6_C10-aryl is substituted one or more times by c〇NH2 or so2nh2; fluoro group; carbyl group; bromo group; cf3; or ocf3. More preferably, one or more of R1 to R5 in the above formula (IV) represents fluorine 15 or gas. The most preferred R1 or R5 represents fluorine. More preferably, in the above formula (IV), one or more of R1 to R5 represents a fluorenyl group; C!-C6-alkoxy, c6-c10-aryloxy, c6-C10-aryl-CrC6 - an alkoxy group, a CrC6-alkyl group, a C6-C1()-aryl group, a crC6-alkyl group, a C6-C1 group, each of which is selectively Each of 20 replaced one or more times: C1_C6_alkyl, CrCV alkoxy, selectively

Ci-CV烧基或Ce-Cur芳基取代一或二次之c〇NH2或 S02NH2、胺基、crc4-烷基胺基、二_Ci_c4j基胺基、羥基、氟代基、氣代基、溴代基、CF3或〇CF3。 76 200932732 更佳R2、R3或R4中之一者代表羥基；CrC6_烷氧基、 CVCw芳氧基、C6-C10-芳基-CrC6-烧氧基，其中各者選擇性地被下列各者取代一或多次：Crc4_烷基、Ci_c4_烷氧基、選擇性地被Q-CV烷基或c6_ClQ_芳基取代一或二次之 5 C0NH2或s〇2NH2、胺基、Q-C4-烷基胺基、二-CrC4-烷基胺基、羧基、氟代基、氣代基或溴代基。在上述化學式(IV)中，更佳R1至R5中之一或多者代表胺基；經選自CkC6-烷基、C6-C1(r芳基的殘基取代一或多次之 ® 胺基；或具下列化學式（II)之一種經二取代的胺基：Ci-CV alkyl or Ce-Cur aryl substituted one or two times c〇NH2 or S02NH2, amine group, crc4-alkylamino group, di-Ci_c4j-based amine group, hydroxyl group, fluoro group, gas group, Bromo, CF3 or 〇CF3. 76 200932732 More preferably one of R2, R3 or R4 represents a hydroxyl group; CrC6_alkoxy, CVCw aryloxy, C6-C10-aryl-CrC6-alkoxy, each of which is selectively selected by the following Substituted one or more times: Crc4_alkyl, Ci_c4_alkoxy, 5 C0NH2 or s〇2NH2, amine group, Q-C4, optionally substituted by Q-CV alkyl or c6_ClQ_aryl An alkylamino group, a di-CrC4-alkylamino group, a carboxyl group, a fluoro group, a carbyl group or a bromo group. In the above formula (IV), more preferably one or more of R1 to R5 represents an amine group; an amine group substituted one or more times by a residue selected from a CkC6-alkyl group and a C6-C1 (raryl group) Or a disubstituted amine group of the following formula (II):

其中0代表0或1，而W代表氧、CH2或NR6，R6係選自氫與CrC4_烷基’及其中化學式(π)中的亞甲基可選擇性地被C1-C4-烧基、氟代基或氣代基取代一或二次。更佳R2、R3或R4中之一者代表胺基；被選自Q-CV炫 15 基、C6-C1()-芳基的殘基取代一或二次之胺基；或具下列化學式(II)之一種經二取代的胺基：Wherein 0 represents 0 or 1, and W represents oxygen, CH2 or NR6, and R6 is selected from hydrogen and CrC4-alkyl and the methylene group in the formula (π) is optionally C1-C4-alkyl, The fluoro group or the gas group is substituted one or two times. More preferably, one of R 2 , R 3 or R 4 represents an amine group; an amine group substituted with one or two substituents selected from the group consisting of Q-CV H- 15 or C 6-C 1 ()-aryl; or the following chemical formula ( II) A disubstituted amine group:

—N W—N W

° (Π) 其中〇代表〇或1，而w代表氧、CH2或NR6，R6係選自氫與Q-Cr烷基，及其中化學式(II)中的亞甲基可選擇性地 20 被C1-C4-烧基、敗代基或氯代基取代一或二次。在上述化學式(IV)中，更佳η代表〇 ; m代表〇、1、2、 3、4、5或6 ;及Y代表C3-C6-環烷基或c6-C10-芳基，其中 77 200932732 各者選擇性地被下列各者取代一或多次： ajCrCV烷基、C6-C1()-芳基、C6-C1(r 芳基-CrC4-烷基、Ci_C6_烧氧基、C6-Ci〇-芳氧基、C6-Ci〇-芳基-C1-C4-烧氧基； 5 其中各者選擇性地被下列各者取代一或多次：CrC6-° (Π) where 〇 represents 〇 or 1, and w represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and Q-Cr alkyl, and the methylene group in the formula (II) is optionally 20 by C1 The -C4-alkyl, hydroxy or chloro group is substituted one or two times. In the above formula (IV), more preferably η represents 〇; m represents 〇, 1, 2, 3, 4, 5 or 6; and Y represents C3-C6-cycloalkyl or c6-C10-aryl, wherein 77 200932732 Each is optionally replaced by one or more of the following: ajCrCV alkyl, C6-C1()-aryl, C6-C1 (r aryl-CrC4-alkyl, Ci_C6_alkoxy, C6- Ci〇-aryloxy, C6-Ci〇-aryl-C1-C4-alkoxy; 5 each of which is optionally substituted one or more times by: CrC6-

烷基；CrCV烷氧基；選擇性地被CVCV烷基取代一或二次之CONH2或S02NH2 ; S03H ; C02H ;胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、 C6-Ci〇-芳基、C6-Ci〇-芳基-C1-C4-烧基、Ci_C6-烧基幾 10 基、C6-C1()-芳基羰基、C丨-c6-烷基磺醯基及c6-c1()-芳基磺醯基；硫氩基；羥基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；cf3 ;或OCF3 ; 或被：An alkyl group; a CrCV alkoxy group; a CONH2 or S02NH2 which is optionally substituted one or two times with a CVCV alkyl group; S03H; C02H; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of: Crc6-alkyl, C6-Ci〇-aryl, C6-Ci〇-aryl-C1-C4-alkyl, Ci_C6-alkyl10, C6-C1()-arylcarbonyl, C丨-c6 -alkylsulfonyl and c6-c1()-arylsulfonyl; thioaryl; hydroxy; nitro; cyano; fluoro; chloro; bromo; iodo; cf3; OCF3 ; or by:

b)經基；硫氫基；梢基；氰基；氟代基；氯代基；'/臭 15 代基；碘代基；cf3 ; ocf3 ; co2h ; so3h ;選擇性地被 CkCV烷基取代一或二次之conh2或so2nh2，其中該等選擇性的CVC6-烷基殘基可結合而形成5或6員環；胺基；被 CVCV烷基或苯基取代一或多次之胺基；具下列化學式(II) 之一種經二取代的胺基：b) thiol; sulfhydryl; aryl; cyano; fluoro; chloro; '/ odor 15 base; iodo; cf3; ocf3; co2h; so3h; selectively substituted by CkCV alkyl One or two times of conh2 or so2nh2, wherein the selective CVC6-alkyl residues may be combined to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times by a CVCV alkyl group or a phenyl group; A disubstituted amino group of the following formula (II):

其中〇代表0或1，而w代表氧、CH2或NR6，R6係選自氫與Q-CV烷基，及其中化學式(II)中的亞曱基可選擇性地被心-匸^烷基、氟代基或氯代基取代一或二次； 78 200932732 或被： 5 ❹ 10 15 ❹ 20 c)一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次：Cl_c6_ 垸基；CVC6-烷氧基；COOH ;選擇性地被CVCV烷基取代一或二次之C0NH24S02NH2，其中該等選擇性的cvc6-烷基殘基可結合而形成5或6員環；S03H ;胺基；經選自下列群中的殘基取代一或多次之胺基：Crc6-烷基、c6-c1(r 芳基、c6-c10-芳基-crc4-烧基、CVCV烧基幾基、c6-c1(r 方基Ik基、C〗-C6-烧基績醯基及C6-C1(r芳基項醢基；硫氫基；經基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；CF3 ;或〇CF3。更佳η代表〇 ; m代表0或1 ;及γ代表一苯基、萘基或吼啶基環系統。甚至更佳者係Y被下列各者取代一或多次：Cl_C4_烷基；苯基；Q-C4-烷氧基；羥基；氟代基；氯代基；溴代基；CF3 ; OCF3 ;選擇性地被q-Cr烷基取代一或二次之 conh24so2nh2 ’其中該等選擇性的Cl_C4_烧基殘基可結合而形成5或6員環；或胺基。又更佳者係m代表0，及γ代表被羥基、氟代基、氯代基或溴代基取代一或二次之苯基。最佳m代表〇 ;及γ代表苯基，其在4_位置被氟代基取代、在4-位置被氣代基取代、在2_與4_位置被氟代基取代、在2-與4-位置被風代基取代或在4_位置被苯基取代。在上述化學式(IV)中，特佳„!為〇 ; η為〇 ; γ代表被氟代 79 200932732 基、乳代基或漠代基取代一或二次之笨基·，及R2至R4中之任一者代表OR7，其中R7係選自氫與Ci_C4_烷基。在上述化學式(IV)中，亦非常佳者係爪為〇 ; 11為0 ; γ 代表苯基’其在4-位置被氟代基取代、在4_位置被氣代基取 5代、在2-與4-位置被氟代基取代或在2-與4-位置被氣代基取代，及R2至R4中之任一者代表OR7，其中R7係選自氫與 C1-C4-烧基。在上述化學式(IV)中，亦非常佳者係111為〇 ; n為〇 ; γ 代表被氟代基、氣代基或溴代基取代一或二次之苯基，及 ❹ 10 R3或者R3與R4代表羥基。在上述化學式(IV)中，亦非常佳者係m為〇 ; 11為〇 ; γ 代表苯基’其在4-位置被氟代基取代、在4位置被氣代基取代、在2-與4_位置被氟代基取代或在2與4位置被氣代基取代，及R3或者R3與R4代表羥基。 15 在上述化學式(IV)中’特佳11^0 ; η為0 ; Y代表被氟代基、氣代基或溴代基取代一或二次之苯基；以至尺4中之任一者代表OR7，其中R7係選自氫與CrC4_烧基；及表氣。 ❹ 在上述化學式(IV)中，特佳m_; n為G; γ代表苯基，其在4-位置被氟代基取代、在4_位置被氣代基取代在2-20與4-位置被氟代基取代或在2與4位置被氣代基取代；尺2 至R4中之任-者代表〇r7，其中r7係選自氫與烷基；及R1代表氟。在上述化學式(IV)中，特佳岭心為口代表被氣代基、氣代基或溴代基取代n之苯基；r3或者¥與γ 80 200932732 代表經基；及Ri代表氟。在上述化學式(IV)中’特佳m為0; η為G; Y代表苯基，其在4-位置被氟代基取代、在4位置被氣代基取代、在與4-位置被氟代基取代或在2與*位置被氣代基取代；r3 5或者r3與r4代表羥基；及r1代表氟。如下，藉由下列的代表性實例說明本發明：第1例：这氧基-3-(4^^3-基）策某]3 二吨_2(3Η、酮 — a) 在氬氣下，在位於νμρ(20毫升）與《比啶(6.87克，87 10 毫莫耳）的一混合物中之(4-溴苯基)肼(3.13克，14毫莫耳)之經授拌的一冰***液中，逐滴添加氣碳酸苯基酯（2412克， • 15.41毫莫耳）。在〇°C攪拌該反應30分鐘，然後讓其回溫至室溫及攪拌1小時。以水稀釋該反應混合物，及以乙酸乙酯萃取。分別以水與鹽水清洗有機相。以硫酸鎂乾燥之後， 15 加以過濾與蒸發，而得5.5克之黃色油形式的苯基-2-(4-溴苯基)肼羧酸酯’其在靜置後結晶。 b) 在上述中間產物(5.5克)與吼啶(7.37克，83毫莫耳)之冰冷的一混合物中，逐滴添加碳醯氣位於甲苯中的20%溶液(22.6毫升’ 43毫莫耳）。在冷的狀態攪拌該反應混合物3〇 20 分鐘’然後在室溫中攪拌1小時。在反應混合物中通入氬氣，及以0°C的水稀釋。將二相分離，及分別以2N鹽酸、水及鹽水溶液清洗有機相。將有機相與炭一起攪拌30分鐘。然後過濾通過一個氧化矽短墊。在蒸發除去溶劑之後，粗製產物自DCM/IPA混合物中再結晶，而得1.938克之白色固 81 200932732 體形式的3-(4-溴苯基)-5-苯氧基-1，3,4-呋二唑-2(3好)-酮。 (二個步驟的產率為32.5%) c)在3-(4-溴苯基)-5-苯氧基-1，3,4-呋二唑-2(3H)-酮(0.6 克，1.8毫莫耳)於二曱氧基乙烷(20毫升)與水(3毫升）中之經 5 攪拌的一溶液中，添加吡啶-3-基硼酸(0.31克，2.52毫莫耳) 與碳酸鉀(0.647克，4.68毫莫耳）。一旦製得一溶液後，添加 Pd(PPh3)4(0.104克’ 0.09毫莫耳），及該混合物於85°C加熱3 小時，然後讓其冷卻至室溫。在減壓下將溶劑除去，及將殘餘物分溶於2〇%iPrOH-DCM與水之間。過濾該混合物， 10 以協助分層，然後以水與鹽水清洗有機相，接著以硫酸鎂乾燥及過濾至活性碳上。在攪拌10分鐘之後，讓混合物過濾通過一個矽膠/矽藻土短塞，將濾液蒸發而得綠色油，其在靜置後固化。自乙醇中再結晶，而得灰色粉末形式的5- 本乳基-3-(4-批°定-3-基）苯基-1，3，4-β夫二哇-2(3^0-網（〇. 165 15 克，27.7%)，熔點(m.p.)為 146-147°C。第2例： U荒氧基)-3-(3-渙笨基Vl.3,4-咭二吨-2(37/)-酮 a)在氬氣下’在(3-溴苯基)肼鹽酸鹽(5.00克，22.37毫莫耳)與吡啶(8.85克，112毫莫耳)於40毫升NMP中之經攪拌的 20 —冰***液中，逐滴添加氣甲酸苄基酯（8.40克，24.61毫莫耳)於曱苯中的50%溶液。在(Tc攪拌該反應30分鐘，然後讓其回溫至室溫及攪拌1小時。將反應混合物倒入冰水中；將沈澱物濾出，以水清洗，及於乙酸乙酯中以硫酸鎂乾燥。蒸發除去溶劑，而得6.77克之黃色固體形式的苄基_2_(3溴 200932732 苯基)肼羧酸酯（產率為94%)。 5 ❹ 10 15 20 b)在苄基-2-(3-溴苯基）肼羧酸酯（6·77克）與吼啶(8 57 克，110毫莫耳）之冰冷的一混合物中，逐滴添加碳醯氣於甲苯中的20%溶液(26.6毫升，5〇.6毫莫耳）。在冷的狀態攪拌該反應混合物30分鐘，然後在室溫中攪拌丨小時。在反應混合物中通入氬氣，及以〇它的水稀釋。將二相分離，及分別以2N鹽酸溶液、水及鹽水清洗有機相。將有機相與炭一起搜拌30分鐘。然後過滤通過一個氧化石夕短塾。在蒸發除去溶劑之後，粗製產物自乙醇中再結晶，而得476克之米黃色固體形式的5-苄氧基-3-(3-溴苯基）-1,3,4_呋二唑 -2(3好)-酮’溶點(m.p.)為89_9(rc。（產率為65%) 第3例：比咬-3-棊氧)-3-(4-甲氳基笨基)_1.3.4_咭二碎_2Π价躺 a) 在氮氣下，在碳醯氣(52.6毫升，1〇〇毫莫耳)(於甲苯中的20%溶液）位於DCM(25毫升）中之一冰***液中，在i 小時期間分次添加2-溴吡啶-3-酚(3.48克，20毫莫耳)與吡啶 (2.108克’ 26.7毫莫耳)於DCM(50毫升）中之一混合物。讓反應回溫至室溫’再攪拌2小時，然後在反應混合物中通入氮氣30分鐘。在真空中蒸發至乾，與1〇〇毫升甲苯共沸，及在真空中乾燥。製得灰色吸濕性粉末形式的2_溴吡啶_3-基氣碳酸酯（6.59克，93%)。 b) 在氮氣下，在(4-甲氧基苯基)肼鹽酸鹽（1.746克，10.0 毫莫耳）與°比啶(3.95克，50毫莫耳)於15毫升NMP中之經攪拌的一冰***液中，分次添加2_溴吡啶_3_基氣碳酸酯（423 83 200932732 克，12.0毫莫耳）。在0°C攪拌該反應30分鐘，然後讓其回溫至室溫及挽拌1小時。將反應混合物倒入冰水中；以乙酸乙 s旨萃取該混合物’及以硫酸鎮乾燥。在蒸發除去溶劑之後，獲得黃色油，其藉由位於2 : 1的石油醚：乙酸乙醋混合物 5 中之管枉色層分析進行純化，而得1.09克之白色固體形式的2-溴《比啶-3-基2-(4-曱氧基苯基)肼羧酸酯（產率為32 2%)。Wherein 〇 represents 0 or 1, and w represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and Q-CV alkyl, and the fluorenyl group in the formula (II) is optionally selected from a heart-? , fluoro or chloro substituted for one or two; 78 200932732 or by: 5 ❹ 10 15 ❹ 20 c) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, the choice Substituted one or more times by: Cl_c6_ fluorenyl; CVC6-alkoxy; COOH; C0NH24S02NH2 selectively substituted by CVCV alkyl one or two times, wherein the selective cvc6-alkyl residue The group may be bonded to form a 5 or 6 membered ring; S03H; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of Crc6-alkyl, c6-c1 (r aryl, c6-c10 -aryl-crc4-alkyl, CVCV alkyl, c6-c1 (r-square Ik, C-C6-alkyl) and C6-C1 (r-aryl) thiol ; thiol; cyano; fluoro; thiol; bromo; iodo; CF3; or 〇CF3. Better η stands for 〇; m stands for 0 or 1; , naphthyl or acridinyl ring system. Even better is Y Each of the columns is substituted one or more times: Cl_C4_alkyl; phenyl; Q-C4-alkoxy; hydroxy; fluoro; chloro; bromo; CF3; OCF3; The alkyl group is substituted one or two times of conh24so2nh2 'wherein the selective Cl_C4_alkyl residue can be combined to form a 5 or 6 membered ring; or an amine group. Further preferably, m represents 0, and γ represents a hydroxyl group. a fluoro group, a chloro group or a bromo group substituted with one or two phenyl groups. The most preferred m represents hydrazine; and γ represents a phenyl group which is substituted at the 4 position by a fluoro group and is gas at the 4-position. Substituted, substituted by a fluoro group at the 2_ and 4_ positions, substituted by a halo group at the 2- and 4-positions or substituted with a phenyl group at the 4-position. In the above formula (IV), 〇 is 〇; η is 〇; γ represents a stupid base substituted by fluorinated 79 200932732 base, milyl or molybdenyl, and R2 to R4 represents OR7, wherein R7 is selected From hydrogen to Ci_C4_alkyl. In the above formula (IV), it is also very good that the claw is 〇; 11 is 0; γ represents phenyl 'which is substituted at the 4-position by a fluoro group, at the 4 position The gas base is taken for 5 generations, at the 2- and 4-positions. Substituted by a fluoro group or substituted with a gaso group at the 2- and 4-positions, and any of R2 to R4 represents OR7, wherein R7 is selected from hydrogen and C1-C4-alkyl. In the above formula (IV) Among them, very good is 111 is 〇; n is 〇; γ represents a phenyl group substituted by a fluoro group, a gas group or a bromo group for one or two times, and ❹ 10 R3 or R3 and R4 represent a hydroxyl group. In the above chemical formula (IV), it is also very preferable that m is hydrazine; 11 is hydrazine; γ represents phenyl 'which is substituted at the 4-position by a fluoro group, at the 4 position by a gas group, at 2 The 4_ position is substituted by a fluoro group or by a gas group at positions 2 and 4, and R3 or R3 and R4 represent a hydroxyl group. 15 In the above chemical formula (IV), 'excellent 11^0; η is 0; Y represents a phenyl group substituted one or two times with a fluoro group, a gas group or a bromo group; or any one of the feet 4 Represents OR7, wherein R7 is selected from the group consisting of hydrogen and CrC4_alkyl; and surface gas. ❹ In the above formula (IV), particularly preferred m_; n is G; γ represents a phenyl group which is substituted at the 4-position by a fluoro group, and at the 4 position is substituted with a gas group at the 2-20 and 4-positions. Substituted by a fluoro group or substituted with a gaso group at positions 2 and 4; any of the scales 2 to R4 represents 〇r7, wherein r7 is selected from hydrogen and an alkyl group; and R1 represents fluorine. In the above chemical formula (IV), the Tejialing core represents a phenyl group substituted by a gas group, a gas group or a bromo group; r3 or ¥ and γ 80 200932732 represents a thiol group; and Ri represents fluorine. In the above chemical formula (IV), 'excellent m is 0; η is G; Y represents a phenyl group which is substituted by a fluoro group at the 4-position, substituted with a gas group at the 4-position, and fluorine at the 4-position. The substituent is substituted or substituted with a gas group at the 2 and * positions; r3 5 or r3 and r4 represent a hydroxyl group; and r1 represents fluorine. The present invention is illustrated by the following representative examples as follows: Example 1: This oxy-3-(4^^3-yl) is a 3 ton 2 (3 Η, ketone- a) under argon , a mixed solution of (4-bromophenyl)indole (3.13 g, 14 mmol) in a mixture of νμρ (20 ml) and pyridine (6.87 g, 87 10 mmol) In an ice-cold solution, phenyl carbonate (2412 g, • 15.41 mmol) was added dropwise. The reaction was stirred at 〇 ° C for 30 minutes, then allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with water and brine, respectively. After drying over magnesium sulfate, 15 was filtered and evaporated to give 5.5 g of phenyl-2-(4-bromophenyl)indolecarboxylate as a yellow oil which crystallised upon standing. b) In a cold-cooled mixture of the above intermediate product (5.5 g) and acridine (7.37 g, 83 mmol), a 20% solution of carbon helium in toluene (22.6 ml '43 mmol) was added dropwise. ). The reaction mixture was stirred in a cold state for 3 Torr for 20 minutes' and then stirred at room temperature for 1 hour. Argon was bubbled through the reaction mixture and diluted with water at 0 °C. The two phases were separated and the organic phase was washed with 2N hydrochloric acid, water and a brine solution, respectively. The organic phase was stirred with charcoal for 30 minutes. It is then filtered through a short pad of cerium oxide. After removal of the solvent by evaporation, the crude product was recrystallized from DCM/IPA mixture to yield 1.838 g of white solid 81 <RTI ID=0.0>> Furadiazole-2 (3 good)-ketone. (The yield of the two steps is 32.5%) c) In 3-(4-bromophenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one (0.6 g, Adding pyridin-3-ylboronic acid (0.31 g, 2.52 mmol) to carbonic acid in a stirred solution of 5 mM in dimethoxy ethane (20 mL) and water (3 mL) Potassium (0.647 g, 4.68 mmol). Once a solution was prepared, Pd(PPh3)4 (0.104 g '0.09 mmol) was added, and the mixture was heated at 85 °C for 3 hours and then allowed to cool to room temperature. The solvent was removed under reduced pressure, and the residue was partitioned between 2% i.s. The mixture was filtered, 10 to aid in stratification, then the organic phase was washed with water and brine, then dried over magnesium sulfate and filtered onto activated carbon. After stirring for 10 minutes, the mixture was filtered through a silica gel/diatomaceous earth plug, and the filtrate was evaporated to give a green oil which solidified after standing. Recrystallized from ethanol to give 5-yrylacyl-3-(4-b-but-3-yl)phenyl-1,3,4-beta-fu-wow-2 (3^0) as a gray powder - mesh (〇. 165 15 g, 27.7%), melting point (mp) 146-147 ° C. Example 2: U-decyloxy)-3-(3-indole-based Vl.3,4-咭2 Tonne-2(37/)-ketone a) under argon' in (3-bromophenyl)phosphonium hydrochloride (5.00 g, 22.37 mmol) with pyridine (8.85 g, 112 mmol) at 40 A 50% solution of benzyl formate (8.40 g, 24.61 mmol) in toluene was added dropwise to a stirred 20-ice cold solution in EtOAc. The reaction was stirred for 30 minutes (Tc, then allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was poured into ice water; the precipitate was filtered, washed with water and dried over magnesium sulfate The solvent was evaporated to give 6.77 g of benzyl-2-(3br. 200932.32 phenyl) phthalic acid ester as a yellow solid (yield: 94%). 5 ❹ 10 15 20 b) in benzyl-2-( A 20% solution of carbon helium in toluene was added dropwise to a cold-cooled mixture of 3-bromophenyl)indolecarboxylate (6.97 g) and acridine (8 57 g, 110 mmol). 26.6 ml, 5 〇.6 mmol.) The reaction mixture was stirred in a cold state for 30 minutes and then stirred at room temperature for a few hours. Argon was bubbled through the reaction mixture and diluted with water. The two phases were separated and the organic phase was washed with 2N hydrochloric acid solution, water and brine, respectively. The organic phase was mixed with charcoal for 30 minutes. It is then filtered through an oxidized stone. After removal of the solvent by evaporation, the crude product was recrystallized from ethanol to give 476 g of 5-benzyloxy-3-(3-bromophenyl)-1,3,4-furodiazole-2 as a beige solid. (3 good)-ketone's melting point (mp) is 89_9 (rc. (yield is 65%). Example 3: bite -3-oxooxy)-3-(4-methylmercapto). 3.4_咭二碎2 Π 躺 lie a) ice-cold solution in carbon monoxide (52.6 ml, 1 〇〇 millimolar) (20% solution in toluene) in DCM (25 ml) under nitrogen A mixture of 2-bromopyridin-3-ol (3.48 g, 20 mmol) and one of pyridine (2.108 g '26.7 mmol) in DCM (50 mL) was added portionwise. The reaction was allowed to warm to room temperature and stirred for additional 2 hours, then nitrogen was passed through the reaction mixture for 30 min. Evaporate to dryness in vacuo, azeotrope with 1 mL of toluene, and dry in vacuo. 2-Bromopyridine-3-yl carbonate (6.59 g, 93%) was obtained as a gray hygroscopic powder. b) Stirring with (4-methoxyphenyl)phosphonium hydrochloride (1.746 g, 10.0 mmol) and pyridine (3.95 g, 50 mmol) in 15 mL of NMP under nitrogen. In an ice-cold solution, 2_bromopyridine_3_yl carbonate (423 83 200932732 g, 12.0 mmol) was added in portions. The reaction was stirred at 0 ° C for 30 minutes, then allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was poured into ice water; the mixture was extracted with ethyl acetate and dried over sulfuric acid. After evaporation of the solvent, a yellow oil was obtained, which was purified by EtOAc EtOAc (EtOAc:EtOAc: 3-yl 2-(4-decyloxyphenyl)indolecarboxylate (32 2% yield).

c)在2-溴°比啶-3-基2-(4-甲氧基苯基）肼羧酸酯（1 .〇71 克’ 3.17毫莫耳)與吡咬(1.303克，16.47毫莫耳)之一冰冷混合物中，逐滴添加碳醯氣於甲苯中的20%溶液(4 〇毫升，7 6 Q 10 毫莫耳）。在冷的狀態攪拌該反應混合物30分鐘，然後在室溫中攪拌1.5小時。在反應混合物中通入氮氣，及以〇。(：的 - 水稀釋。將二相分離，及以DCM萃取水相。合併後的有機相以硫酸鎂乾燥，及加以過濾。在蒸發作用後，藉由位於2 : 1的石油醚：乙酸乙酯混合物中之管柱色層分析，純化粗製 15 的5_(2-溴°比咬_3_基氧）-3-(4-曱氧基苯基）-1，3,4-呋二唑 -2(3//)-酮。產生75毫克的米黃色粉末(6.50%);熔點為116 5_c) in 2-bromo-pyridin-3-yl 2-(4-methoxyphenyl)indole carboxylate (1. 〇71 g ' 3.17 mmol) with a pyridine bite (1.303 g, 16.47 mmol) In an ice-cold mixture, a 20% solution of carbon helium in toluene (4 mL, 7 6 Q 10 mmol) was added dropwise. The reaction mixture was stirred in a cold state for 30 minutes and then stirred at room temperature for 1.5 hours. Nitrogen gas was introduced into the reaction mixture, and helium was introduced. (: - Water dilution. Separate the two phases and extract the aqueous phase with DCM. The combined organic phases are dried over magnesium sulfate and filtered. After evaporation, with petroleum ether: 2:1 Column chromatography analysis in ester mixture, purification of crude 15 5-(2-bromo-bito_3_yloxy)-3-(4-decyloxyphenyl)-1,3,4-furadiazole -2(3//)-ketone. Produced 75 mg of beige powder (6.50%); melting point 116 5_

117.5。。。 Q 第4例： til-、/臭-2-ΐ_氧皋笨氣某芣苹-1 '4-4 -呻_〇^ m 2〇 a)在4-溴-2-甲氧基苯酚(4.〇6克，20毫莫耳）與碳醯氯 (11.58毫升，22.00毫莫耳)之經攪拌的一冰***液中，逐滴添加溶於甲苯(9毫升）中之N，N_二甲基苯胺(2424克，2〇〇〇毫莫耳）。在室溫中攪拌該反應3小時。在反應混合物中通入氮氣30分鐘；及以冰驟冷。分別&1N鹽酸溶液與水清洗 84 200932732 有機相。以硫酸鎂乾燥之後，藉由真空除去甲苯，而得油形式的4-漠-2-曱氧基氯碳酸苯基醋。產率：4.1〇克，77%。 5 ❹ 10 15 20 b) 在笨基肼（1.081克，1〇.〇毫莫耳）與吡啶(3 95克，50 毫莫耳)於15毫升NMP中之經攪拌的一冰***液中，分次添加4-溴-2-甲氧基氣碳酸苯基酯(3.19克，12.0毫莫耳）。在室溫中援拌該反應1小時。然後倒入冰-1N鹽酸混合物；將沈澱物濾出，以水清洗及於真空中乾燥。藉由以石油醚研製，而得白色粉末形式的4-溴-2-甲氧基苯基2_苯基肼羧酸酯。產率：3,38克。 c) 在4-溴-2-甲氧基苯基2-苯基肼敌酸酯（3·2〇克，949 毫莫耳)與吼咬(3.90克，49.4毫莫耳)之一冰冷混合物中，逐滴添加碳醯氣於甲笨中的20%溶液（U.98毫升，22 78毫莫耳）。在冷的狀態檀拌該反應混合物15分鐘，然後在室溫中攪拌45分鐘。在反應混合物中通入氮氣，及以〇c>c的水稀釋。將二相分離，及分別以1N鹽酸與水清洗有機相。以硫酸鎂乾燥之後，藉由真空除去溶劑。藉由位於1〇 :丨的石油醚：乙酸乙酯混合物中之管柱色層分析，純化5_(4_溴_2甲氧基苯氧基)-3-苯基-1,3,4-呋二唑酮。產率：i 198 克的白色粉末，318% ;熔點為77-78°C。第5例： 1:(4-取,本乳基)-3-(4-經基笨基)-1,3.4-4 二4-2(3出-_ a)在室溫中，在4-甲氧基苯基肼鹽酸鹽(6克，344毫莫耳）於N-甲基-2-吡咯烷酮（48毫升）中之經攪拌的一溶液中，逐滴添加吡啶（13.89毫升，172毫莫耳），將所產生的溶 85 200932732 液冷卻至0°C。在其中逐滴添加4-氣氣碳酸苯基酯（5 29毫升，37.8毫莫耳）。所產生的溶液在(TC攪拌3〇分鐘，然後讓其回溫至室溫及攪拌1小時。將反應混合物倒入冰/水中，及攪拌1小時。將沈澱物濾出，以水清洗及乾燥。自異丙醇 5 中再結晶，而得一白色固體形式的4-氯苯基2-(4-甲氧基苯基)肼羧酸酯（5.74克，57%)。 b) 在室溫中，在4-氯苯基2-(4-甲氧基苯基）肼羧酸酯 (5.74克，19.61毫莫耳)於二氣甲烷（150毫升）中之經攪拌的 —溶液中，添加"比唆(8.25毫升，1〇2毫莫耳），將所產生的 1〇溶液冷卻至(TC。然後逐滴添加碳醯氯(24.76毫升，47.1毫莫耳)於甲苯中的20%溶液。該混合物於〇°c攪拌3〇分鐘，然後讓其回溫至室温及授拌1小時。在混合物中通入氮氣3〇分鐘’然後冷卻至0°C及以水稀釋。將相分離，及以2N鹽酸、水與鹽水清洗有機相’然後乾燥（硫酸鎂）及過濾至活性碳 15 上。在攪拌15分鐘之後，讓懸浮液過濾通過一個氧化矽與矽藻土短墊。將濾液蒸發，所產生的黃色固體自異丙醇中結晶二次，而得一白色固體形式的5-(4-氣苯氧基)-3-(4-甲氧基苯基)-1,3,4-呋二唑-2(3H)-酮(3.14克，50%)。 c) 在氮氣下，將5-(4-氯苯氧基）-3-(4-曱氧基苯 20 基)-1，3,4-呋二唑-2(3H)-酮(3.14克，9.85毫莫耳)於二氣甲烷 (30毫升）中之經攪拌的一溶液冷卻至_8〇°C(懸浮液），及逐滴添加三溴化硼（1.863毫升，19.70毫莫耳）。所產生的淡粉紅色溶液於-80°C授拌5分鐘，然後讓其回溫至室溫及攪拌2小時。將反應混合物冷卻至0°C，及小心地添加冰/水。將所產生的 200932732 沈澱物過濾，以水清洗及乾燥。自異丙醇中再結晶，而得一白色固體形式的5-(4-氣苯氧基)-3-(4-羥基苯基)-1，3,4-呋二唑 -2(3H)-_(2.2克，73%)，熔點為 163.5-164.5t：。第6例： 5 e 10 15 ❹ 20 liH-胺基苯基)-5-(2,4-二氟茉氳某)m处二唑 a) 在室溫中，在3-硝基苯基肼鹽酸鹽（1克，5.27毫莫耳) 於N-甲基-2-n比洛院酮（8毫升）中之經授拌的一溶液中，逐滴添加吼啶(2.13毫升，26.4毫莫耳）。將所產生的混合物冷卻至〇。(：，及逐滴添加2,4-二氟氣碳酸苯基酯（1·22克，6.33毫莫耳）。所產生的混合物於0°C攪拌30分鐘，然後在室溫中攪拌1小時，及將其倒在冰/水上。以乙酸乙酯萃取該混合物，及以2N鹽酸、水及鹽水清洗有機萃取物，然後乾燥(硫酸鎂），加以過濾與蒸發，而得一黃色油形式的2,4二氟苯基2-(3-确基苯基)肼缓酸酯（16克，1〇〇%)。 b) 在室溫中，在2,4-二氟苯基2_(3“肖基苯基)肼緩酸醋 (1.7克，5.50毫莫耳)於二氯曱烧(3〇毫升）中之一溶液中，逐滴添加錢(2.312毫升，28.6毫莫耳），及將該溶液冷卻至〇 °C。逐滴添加碳醯氣(6.94毫升，1319毫莫耳）於甲苯中的 20%溶液。所產生的粉紅色料液於此麟聊鐘，然後讓其回溫至室溫及攪拌^、時。在混合物巾通人氮氣％分鐘，然後冷卻至(TC及以水稀釋。將相分離’及以抓鹽酸、水與鹽水清洗有機相’然後乾燥(硫_)，加以過據盘蒸發。所產生的黃色油藉由色層分娜A臓的石油醚/乙酸 ⑽）純化。將含有純產物的分液匯集，及蒸發而得—粉紅 87 200932732 色油，其在靜置後固化。自庚烷與二乙基醚中結晶，而得一白色固體形式的5-(2,4-二氟苯氧基）-3-(3-硝基苯基)_1，3,4_ 呋二唑-2(3H)-酮(260毫克，14%)。 c)在室溫及氮氣下，在5-(2,4-二氟苯氧基)-3-(3-硝基苯 5 基)-1,3,4-呋二唑-2(3H)-酮（251毫克，0.749毫莫耳）於甲醇 (20毫升）中之經攪拌的一懸浮液中，添加10%碳鈀（25毫克）。然後在反應混合物中通入氫氣1小時。讓該反應混合物過濾通過一個矽藻土短墊，及將濾液蒸發。所產生的黃色固體藉由管柱色層分析（6/1至4/1的石油醚/乙酸乙酯）純 10 化。將均質分液匯集及加以蒸發，所產生的淡黃色固體自異丙醇中結晶，而得一淡黃色固體形式的3_(3-胺基笨基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑·2(3Η)-酮（128毫克， 56%)，熔點為 122-123°C。第7例： 15 20117.5. . . Q Example 4: til-, / odor -2- ΐ 皋皋皋芣芣 ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' ' 4. 〇6g, 20mmol) and a stirred ice-cold solution of carbon ruthenium chloride (11.58 ml, 22.00 mmol), N, N_ dissolved in toluene (9 ml) Methyl aniline (2424 g, 2 〇〇〇 millimolar). The reaction was stirred at room temperature for 3 hours. Nitrogen gas was bubbled through the reaction mixture for 30 minutes; and quenched with ice. Separate & 1N hydrochloric acid solution with water 84 200932732 Organic phase. After drying over magnesium sulfate, toluene was removed by vacuum to give 4-diethyl-2-indoleoxychlorocarbonate in the form of oil. Yield: 4.1 g, 77%. 5 ❹ 10 15 20 b) In a stirred ice-cold solution of stupid base (1.081 g, 1 〇. 〇mol) with pyridine (3 95 g, 50 mmol) in 15 ml of NMP 4-Bromo-2-methoxycarbonic acid phenyl ester (3.19 g, 12.0 mmol) was added in portions. The reaction was stirred for 1 hour at room temperature. The ice- 1N hydrochloric acid mixture was then poured; the precipitate was filtered off, washed with water and dried in vacuo. 4-Bromo-2-methoxyphenyl-2-phenylindolecarboxylate was obtained as a white powder by trituration with petroleum ether. Yield: 3,38 g. c) an icy mixture of 4-bromo-2-methoxyphenyl 2-phenyl phthalate (3·2 gram, 949 mM) with one bite (3.90 g, 49.4 mmol) A 20% solution of carbon helium in a stupid (U. 98 ml, 22 78 mmol) was added dropwise. The reaction mixture was mixed in a cold state for 15 minutes and then stirred at room temperature for 45 minutes. Nitrogen gas was introduced into the reaction mixture, and diluted with water of 〇c>c. The two phases were separated and the organic phase was washed with 1 N hydrochloric acid and water, respectively. After drying with magnesium sulfate, the solvent was removed by vacuum. Purification of 5-(4-bromo-2-methoxyphenoxy)-3-phenyl-1,3,4- by column chromatography in a petroleum ether:ethyl acetate mixture of hydrazine: Furadiazolone. Yield: i 198 g of white powder, 318%; m.p.: 77-78. Case 5: 1: (4-take, the present lactidyl)-3-(4-pyrimidinyl)-1,3.4-4 2-4-2 (3 out-_a) at room temperature, at 4 -Methoxyphenylhydrazine hydrochloride (6 g, 344 mmol) in a stirred solution of N-methyl-2-pyrrolidone (48 ml), pyridine (13.89 mL, 172) Millol), the resulting solution 85 200932732 solution was cooled to 0 °C. A 4-carbon phenyl carbonate (5 29 ml, 37.8 mmol) was added dropwise thereto. The resulting solution was stirred at TC for 3 minutes, then allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was poured into ice/water and stirred for 1 hour. The precipitate was filtered, washed with water and dried. Recrystallization from isopropanol 5 gave 4-chlorophenyl 2-(4-methoxyphenyl)indolecarboxylate (5.74 g, 57%) as a white solid. In a stirred solution of 4-chlorophenyl 2-(4-methoxyphenyl)phosphonium carboxylate (5.74 g, 19.61 mmol) in di-methane (150 mL), " 唆唆 (8.25 ml, 1 〇 2 mmol), the resulting 1 〇 solution was cooled to (TC. Then add carbon bismuth chloride (24.76 ml, 47.1 mmol) to 20% in toluene The mixture was stirred at 〇 °c for 3 minutes, then allowed to warm to room temperature and stirred for 1 hour. Nitrogen was bubbled through the mixture for 3 ' ' and then cooled to 0 ° C and diluted with water. And washing the organic phase with 2N hydrochloric acid, water and brine' then dried (MgSO4) and filtered onto activated carbon 15. After stirring for 15 minutes, the suspension was filtered through an oxygen The crucible and the diatomaceous earth were short-padded. The filtrate was evaporated, and the resulting yellow solid was crystallized twice from isopropanol to give 5-(4-phenoxy)-3-(4-methyl) as a white solid. Oxyphenyl)-1,3,4-furadiazole-2(3H)-one (3.14 g, 50%) c) 5-(4-chlorophenoxy)-3- under nitrogen (4-Phenoxybenzene 20-yl)-1,3,4-furadiazole-2(3H)-one (3.14 g, 9.85 mmol) stirred in di-methane (30 mL) The solution was cooled to _8 ° C (suspension), and boron tribromide (1.863 ml, 19.70 mmol) was added dropwise. The resulting pale pink solution was mixed at -80 ° C for 5 minutes, then allowed to warm to room temperature and stirred for 2 hours. The reaction mixture was cooled to 0 ° C and ice/water was carefully added. The resulting 200932732 precipitate was filtered, washed with water and dried. Recrystallization from isopropanol gave 5-(4-phenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2 (3H) as a white solid. -_ (2.2 g, 73%), melting point 163.5-164.5 t:. Example 6: 5 e 10 15 ❹ 20 liH-aminophenyl)-5-(2,4-difluoromethane) m at the diazole a) at room temperature in 3-nitrophenylhydrazine Hydrochloride (1 g, 5.27 mmol) A solution of a solution of N-methyl-2-n bicarolone (8 ml) was added dropwise with acridine (2.13 mL, 26.4 m) Moore). The resulting mixture was cooled to hydrazine. (:, and 2,4-difluorocarbonate phenyl ester (1·22 g, 6.33 mmol) was added dropwise. The resulting mixture was stirred at 0 ° C for 30 minutes and then stirred at room temperature for 1 hour. And pour it on ice/water. The mixture is extracted with ethyl acetate, and the organic extract is washed with 2N hydrochloric acid, water and brine, then dried (MgSO4), filtered and evaporated to give a yellow oil. 2,4 difluorophenyl 2-(3-decylphenyl) hydrazide (16 g, 1%) b) 2,4-difluorophenyl 2_(3) at room temperature "Schottyl Phenyl" to soak the acid vinegar (1.7 g, 5.50 mmol) in a solution of dichlorohydrazine (3 ml), add money (2.312 ml, 28.6 mmol), and The solution was cooled to 〇 ° C. A 20% solution of carbon helium (6.94 ml, 1319 mmol) in toluene was added dropwise. The resulting pink liquid was liquefied and then allowed to warm back. To room temperature and stirring, the mixture was purged with nitrogen for 1 minute, then cooled to (TC and diluted with water. Separate the phases and wash the organic phase with hydrochloric acid, water and brine' then dry (sulfur_) And According to the evaporation of the disk, the yellow oil produced is purified by the color layer of petroleum ether/acetic acid (10). The liquid containing the pure product is collected and evaporated to obtain - pink 87 200932732 color oil, which is allowed to stand. After solidification, crystallized from heptane and diethyl ether to give 5-(2,4-difluorophenoxy)-3-(3-nitrophenyl)_1,3,4_ as a white solid. Furadiazole-2(3H)-one (260 mg, 14%) c) 5-(2,4-difluorophenoxy)-3-(3-nitrobenzene) at room temperature under nitrogen Addition of 10% carbon palladium to a stirred suspension of 5,1,3,4-furadiazole-2(3H)-one (251 mg, 0.749 mmol) in methanol (20 mL) (25 mg). Hydrogen was then introduced into the reaction mixture for 1 hour. The reaction mixture was filtered through a short pad of diatomaceous earth and the filtrate was evaporated. The resulting yellow solid was analyzed by column chromatography (6/1) To a 4/1 petroleum ether/ethyl acetate) purely 10. The homogeneous fractions were combined and evaporated, and the resulting pale yellow solid was crystallized from isopropyl alcohol to give a pale yellow solid. Amino-based)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole · 2(3Η)-ketone (128 mg, 56%), melting point 122-123 ° C. Example 7: 15 20

(4-(1Η-° 比咯-!；；基）苯基)-5-(2,4-二氣笨氳某(4-(1Η-° 比咯-!;; base) phenyl)-5-(2,4-two gas awkward

3-(4-胺基苯基）-5-(2,4-二氟苯氧基）_13,4·吱二η -2_-嗣(203毫克，0.665毫莫耳)與2,5_二甲氧基四氯^ (0.108毫升，0.832毫莫耳)於乙酸(1〇毫升）中之經攪拌的^ 溶液，於95°C加熱1小時，而變成一深紅色溶液。讓混合存冷卻至室溫，及蒸發除去溶劑。在殘餘物巾添再次蒸發。以騎的乙醇研製殘餘物，在熱的狀態過淚2 及以乙醇清洗。在乾燥之後，製得— 心〜无表侍、红褐色固體 3-(4-(m-t各-1-基）苯基)-5_(2,4_二氟笨氧基)^4·咬二口 88 200932732 -2(3H)-酮（109毫克 ’ 46%)，熔點為 181-182°C。第8例：丄-(3’-甲氧基聯夫二峰二2(3出嗣在氣氣下’在3-(4-溴苯基）_5-苯氧基-1，3,4_呋二唑 5 _2(3Η)·_(526毫克，^58㈣耳）、3-甲氧基苯基職(336 毫克，2.21毫莫耳)與碳酸鉀(567毫克，4 1〇毫莫耳)於二甲氧基乙烷（20毫升）與水（1〇毫升）中之經攪拌的—懸浮液中，添加四（三苯基膦）鈀(〇)(91毫克，0.079毫莫耳）。所產生的混合物於85°C攪拌3小時，然後讓其冷卻至室溫。蒸發 10除去溶劑，將殘餘物分溶於二氣甲院與水之間。將有機相分離，以水與鹽水清洗，然後乾燥（硫酸鎂）及過濾至活性碳上。在攪拌10分鐘之後，讓懸浮液過濾通過一個矽膠/碎藻土短塾，將據液蒸發，而留下一油，其在靜置後固化。自一氯甲烷/乙醇中再結晶，而得白色晶體形式的3_(3，甲氧基 15聯苯基_4_基)_5_苯氧基-1，3,4-呋二唑-2(3H)-酮（182毫克， 32%)，熔點為 1〇2-1〇3。(：。第9例： ^~(2,4-二稱_苯氧基)-3-(4-經基苯某,3.4-4 二4-2(3H)-酮 a)在室溫中，在4-甲氧基苯基肼鹽酸鹽(6克，34 4毫莫 2〇耳）於N_甲基_2_吡咯烷酮（48毫升）中之經攪拌的一溶液中，逐滴添加°比咬（13.89毫升，172毫莫耳），及將所產生的溶液冷卻至(TC。然後逐滴添加2,4-二氟氯碳酸苯基酯（7_94 克，41.2毫莫耳）。該溶液於〇°c攪拌3〇分鐘，然後讓其回溫至室溫及攪拌2小時。將反應混合物倒入冰/水中，及攪拌1 89 200932732 小時。以乙酸乙酯萃取該混合物，及以2N鹽酸、水及鹽水清洗有機萃取物’然後乾燥(硫酸鎂）及過濾至活性碳上。在攪拌15分鐘之後，讓懸浮液過濾通過一個矽膠與矽藻土短墊。將濾液蒸發，所產生的黃色油自異丙醇中結晶，而得 5 一白色固體形式的2,4-二氟苯基2-(4-甲氧基苯基)肼羧酸酯 (3.82克，38%)。 b)在室溫中，在2,4-二氟苯基2-(4-甲氧基苯基)肼羧酸酯（3.82克’ 12.98毫莫耳)於二氯甲烷（120毫升）中之經攪拌的一溶液中，逐滴添加吡啶(5.46毫升，67.5毫莫耳），及將 10 所產生的溶液冷卻至(TC。在其中逐滴添加碳醯氣(16.39毫升’ 31.2毫莫耳)於甲苯中的20%溶液。所產生的橘色溶液於〇°C攪拌30分鐘，然後讓其回溫至室溫及攪拌1小時。在混合物中通入氮氣3〇分鐘，然後冷卻至(TC及以水稀釋。將相分離’及以2N鹽酸、水與鹽水清洗有機相，然後乾燥(硫 15 酸鎂），及過濾至活性碳上。在攪拌30分鐘之後，讓懸浮液過濾通過矽膠與矽藻土的短墊。將濾液蒸發，所產生的淡黃色固體自異丙醇中結晶，而得一白色固體形式的5-(2,4- 二氟苯氧基)-3-(4-曱氧基苯基)_ι，3,4-呋二吐-2(3H)-酮(1.77 克 ’ 43%)。 20 c)在氮氣下，將5·(2,4-二氟苯氧基）-3-(4-甲氧基笨基)-1，3,4_呋二唑-2(3Η)-酮(241毫克，0.753毫莫耳)於二氣甲烷(5毫升）中之經攪拌的一溶液冷卻至_80。(：，及逐滴添加三溴化硼(0.142毫升，1.505毫莫耳）。該溶液於-80°C攪拌5 分鐘，然後讓其回温至室溫及攪拌丨小時。然後將反應混合 200932732 物冷卻至o c ’及藉由添加水而小心地驟冷。以位於二氣甲烷中的30%異丙醇萃取該混合物，以水與鹽水清洗合併後的有機層，然後乾燥(硫酸鎂），加以過濾與蒸發。所產生的灰白色固體自異丙醇中結晶，而得一白色固體形式的 5 5_(2,4-二氟苯氧基)-3-(4-經基苯基)-1,3,4-呋二唑_2(3H)-酮 (158毫克 ’ 69%)，熔點為 174.5-176X：。第10例： K4-氣本乳基)-3-(2-氟-4-經基苯基)-1，3,4-°夫二4_2(3!^)-酿1 a) 在室溫中’在3-氟-4-墙基苯紛(5克，31.8毫莫耳)於 10 丙酮（100毫升）中之經攪拌的一溶液中，一次添加碳酸鉀 (15.40克，111毫莫耳）’接著逐滴添加硫酸二甲基醋（6 〇4 毫升，63.7毫莫耳）。所產生的黃色懸浮液在迴流狀態攪拌2 小時。然後將反應混合物冷卻至室溫，加以過遽及將滤液蒸發。所產生的黃色液體藉由管柱色層分析(9/1的石油醚/ 15 乙酸乙醋）純化。將均質分液匯集及蒸發，所產生的黃色油自二乙基醚/石油醚中結晶，而得淡黃色晶體形式的2_氟_4_ 甲氧基-1-硝基苯(2.81克，52%)。 b) 在室溫及氮氣下，在2-氟-4-甲氧基-1-硝基苯(2.76 克，16.13毫莫耳)於甲醇(5〇毫升）中之經授拌的一溶液中， 20 添加10%碳鈀(276毫克）。在反應混合物中通入氫氣1小時，讓懸浮液過濾通過一個矽藻土短墊。將濾液蒸發，所產生的紅色油以石油醚研製。將所產生的橘色固體濾出，及乾燥而得2-氟-4-甲氧基苯胺(2·2克，97%)。 c) 在-10 C，在2-氟-4-甲氧基苯胺(2J3克，15.09毫莫耳） 91 200932732 於濃鹽酸（13.97毫升）中之經攪拌的一溶液中，逐滴添加亞石肖酸納（1·121克’ 16.25毫莫耳)於水(6.96毫升）中的一溶液，同時將溫度維持於_1(rc以下。所產生的混合物於_1(rc攪掉 1小時。在其中逐滴添加氯化錫(II)二水合物(2.90毫升，34 8 5毫莫耳)於濃鹽酸(11.61毫升）中的一溶液，同時將溫度維持於-5°C以下。該反應混合物於_rc攪拌丨小時，然後讓其回溫至室溫。將米黃色懸浮液過濾，將濾餅溶於水中，及藉由添加3N氫氧化鈉水溶液，使得所產生的溶液變成鹼性。然後以一氣甲炫萃取該混合物，以水與鹽水清洗合併後的 10 萃取物，然後乾燥（硫酸鎂），加以過濾與蒸發。所產生的暗紅褐色固體自二乙基醚/石油醚中結晶，而得一暗粉紅色固體形式的(2-氟-4-甲氧基苯基)肼(1.24克，53%)。 d) 在室溫中，在(2-氟-4-甲氧基苯基)肼(1.22克，7.81毫莫耳）於N-甲基-2-吡咯烧酮（10毫升）中之經擾拌的一溶液 15 中’逐滴添加吡啶(3.16毫升，39.1毫莫耳），及將所產生的溶液冷卻至〇°C。在其中逐滴添加4-氣氣碳酸苯基酯（164〇毫升，11.72毫莫耳）。該溶液於0°C攪拌30分鐘，然後讓其回溫至室溫及攪拌1小時。將反應混合物倒入冰/水中，及攪拌1小時。將沈澱物濾除，以水清洗及加以乾燥，而得一 ° 米黃色固體形式的4_氣苯基2-(2-氟-4-甲氧基苯基)肼叛酸酯(2.5克，1〇〇%)。 e) 在室溫中’在4-氣苯基2-(2-氟-4-曱氧基苯基)肼叛酸 S曰（2.5克’ 8.05毫莫耳)於·•氣甲烧(40毫升）中之經授摔的一溶液中，逐滴添加吡啶(3.38毫升，41.8毫莫耳），及將所產 92 200932732 生的溶液冷卻至οι。然後逐滴添加碳醯氯於甲苯（1〇16毫升I9.31毫莫耳）中的20%溶液。所產生的紅色懸浮液於〇〇c 攪拌30分鐘’然後讓其回溫至室溫及攪拌丨小時。在冷卻至之前，在混合物中通入氮氣30分鐘，及以水稀釋。將相分離，以2N鹽酸、水與鹽水清洗有機相。將有機層乾燥(硫酸鎂），過濾至活性碳上及攪拌3〇分鐘。讓懸浮液過濾通過一個矽膠與石夕藻土短墊。將濾'液蒸發，所產生的黃色固體自異丙醇中結晶二次，而得一米黃色固體形式的5-(4-氯苯氧基)_3_(2_氟 -4-甲氧基苯基)_ι，3,4-呋二唑_2(3H)-酮(1.2克，44%)。 1〇〇在氮氣下，將5_(4-氯苯氧基）-3-(2-氟-4-甲氧基苯基)-1，3,4-呋二唑_2(3Η)-酮（1.2克，3·56毫莫耳)於二氯甲烷 (40毫升）中之經攪拌的一溶液冷卻至_8〇<t，及逐滴添加三溴化硼(0.674毫升，7.13毫莫耳）。該溶液於_8(η：攪拌5分鐘，然後讓其回溫至室溫及游5小時。然後將反應混合物 15冷卻至ot，及藉由添加水而小心地驟冷。添加3〇%異丙醇於一氣〒院中的一混合物，將相分離。以二氣甲烷萃取水相，以水與鹽水清洗合併後的萃取物。將有機層乾燥(硫酸鎂），加以過濾與蒸發。將所產生的綠色固體溶於熱的異丙醇中，及將不可溶物質濾出。將濾液蒸發，殘餘物自二氯 *°甲烷/石油醚中結晶，而得一暗粉紅色固體。將該固體溶於二氣甲烷中，及添加活性碳。在攪拌之後15分鐘，讓懸浮液過濾通過一個矽膠與矽藻土短墊。將濾液蒸發至剩下少量體積，及添加PE。將所產生的固體濾出，以石油醚清洗及加以乾燥，而得一灰白色固體形式的5(4氯笨氧 93 200932732 基)-3-(2-氟_4_經基苯基)]，3,4_吱二唾_2(3H)酮⑽毫克， 33%)，熔點為 180-182°C。第11例： 3-(4-胺U二甲_^基苯企二氟茉氳某Vl a』 -口夫二0坐 5 -2(3H)-酮鹽酸鹽 a)在室溫中’在5-氟-2·硝基苯酴(1〇克，63 7毫莫耳)與碳酸鉀d7·59克’m毫莫耳)於丙酮⑽毫升）中之經授摔的一懸浮液中，逐滴添加甲基碘（1194毫升，191毫莫耳）。該反應混合物於室溫中攪拌4天，然後在減壓下蒸發除去丙 0 Π)酮’及將殘餘物分溶於水與乙酸乙醋之間。以濃鹽酸中和水層。將有機層分離’以水與鹽水清洗，加以乾燥(硫祕） - 及過渡與蒸發，而得-灰白色固體，其自異丙醇/二氣甲@ 中再結晶’而得一灰白色固體形式的4_氣_2_甲氧基小琐基苯(9.6克，88%)。 15 b)在室溫中’在412-甲氧基小硝基苯σ克，40.9毫莫耳)於乙醇(84毫升）中之經授拌的一溶液中，逐滴添加水合肼(5.96毫升，123毫莫耳）。該溶液變成黃色，然後變成亮〇橘色。該反應混合物於loot：攪拌2小時，然後冷卻至〇t。將黃色沈澱物過濾分離，及以冷乙醇清洗。將母液蒸發至 2〇剩下一半體積’然後冷卻至〇t，而形成更多的沈殿物。收集沈澱物及以冷乙醇清洗。將沈澱物合併而得(3甲氧基_4_ 硝基笨基)肼(4.18克，56%)。 c)在0C ’在(3-甲氧基-4-確基笨基)耕(4克，2184毫莫耳）與吼啶(8.83毫升，109毫莫耳）於NMp(4〇毫升）中之經攪 94 200932732 摔的二容液中，逐滴添加2,4-二氟氣碳酸笨基醋(4.63克， 24.02毫莫耳）。該反應混合物於〇。〇授拌15分鐘然後在室溫中授拌45分鐘。然後將溶液倒入冰/1N鹽酸溶液的一混合物中。依序以乙酸乙酉旨、二氣甲烧/異丙醇萃取該產物。以 5鹽水清洗合併後的有機層，加以錢(硫酸鎂)及過渡與蒸發，而得-橘色油。藉由管柱色層分析（氧化石夕，依序為2 : 1與1:1的石油_乙酸乙酉旨），而得一橘色油/固體形式的2,4_ 二氟苯基2-(3-曱氧基-4-硝基苯基)肼羧酸酯(5 84克，79%)。 d)在0C，在2,4-二氟苯基2-(3-甲氧基_4_硝基苯基)肼羧 1〇酸酯（5.84克，17.21毫莫耳)與吡啶(7.24毫升，90毫莫耳)於二氣曱烷（115毫升）中之經攪拌的一溶液中，逐滴添加碳醯氣於甲苯中的20%溶液(21.74毫升，41.3毫莫耳）。該溶液變成暗紅色，於〇°C攪拌15分鐘，然後在室溫中攪拌45分鐘。在;谷液中通入空氣10分鐘，然後添加〇°C的水。將有機層分 15 離，依序以1N鹽酸、水與鹽水清洗，然後加以乾燥(硫酸鎂）及過濾與蒸發，而得一暗紅色油《藉由管柱色層分析(依序為 2 : 1與1 : 1的石油峻/二氯曱烷）’而得一黃色固體，其自異丙醇/二氣甲烷中再結晶’而得5_(2,4_二氟笨氧基)_3 (3甲氧基-4-硝基苯基)-1，3,4-呋二唾-2(3H)-_(722 毫克，11.5%)。 2〇 e)在室溫中，在5-(2,4-二氟苯氧基)-3-(3-甲氧基_4_硝基笨基)-1，3,4-呋二唑-2(3H)-酮(200毫克，0.548毫莫耳)於甲醇毫升）中之經攪拌的一溶液中，添加10%碳鈀（185毫克）。在氫氣環境下，該反應混合物於室溫中揽拌3小時。再添加10%碳鈀催化劑（9毫克），該反應混合物在氫氣下及 95 200932732 室溫中再攪拌2小時。然後讓該溶液過濾通過一個石夕藻土短墊，及以乙酸乙酯清洗矽藻土。將濾液蒸發，而得一褐色固體，其自異丙醇中再結晶，而得一米黃色固體（124毫克）。將其溶於乙酸乙酯（5毫升）中，及冷卻至〇°C，然後逐滴添加 5 位於***中的2N鹽酸(2毫升）。將所形成的沈澱物濾出，以乙酸乙酯清洗及乾燥，而得一米黃色固體形式的3-(4-胺基 -3-甲氧基苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑-2(311)-_ 鹽酸鹽（120毫克，90%)，熔點為186-188。(：。第12例： ❹ 10 K4-胺基-3-(2·甲氮某乙氣某）笑1 V5-(2,4·二I笨氧 ^J-1,3,4-咬二唾-2(3HV酮 a) 在室溫中，在5-氟-2-硝基苯酚(4克，25.5毫莫耳）、碳酸鉀（10.56克，76毫莫耳）與1-氯-2-甲氧基乙烷(5.10毫升，56.0毫莫耳）於DMF(102毫升）中之經攪拌的一懸浮液 15 中，添加碘化鈉(0·191克，1.273毫莫耳）。該反應混合物於 8〇C授拌過夜。再添加1-氣-2-甲氧基乙烧(6.38毫升，70.0 毫莫耳）’及該反應混合物於80°C撥拌4小時。添加水與乙 @ 酸乙酯，將有機層分離。以1N鹽酸中和水層，及以乙酸乙酯萃取。以水清洗合併後的有機層，加以乾燥(硫酸鎂）及過 20濾與蒸發，而得-黃色油。藉由管柱色層分析(6: i的石油醚/乙酸乙酯），而得一透明油形式的4_氟_2_(2甲氧基乙氧基M-硝基苯(2.26g，39%)。 b) 在室溫中，在4-氟-2-(2-甲氧基乙氧基）_〗硝基苯 (2.26克’10.50毫莫耳)於乙醇(21.43毫升）中之經攪拌的一溶 96 200932732 5 e 10 15 ❹ 20 液中’添加水合肼（1.531毫升’ 31·5毫莫耳）。該反應混合物於85°C攪拌3小時。然後將溶液冷卻至〇°C ’而形成一沈澱物。將該固體物過濾分離，及以冷乙醇清洗。將母液蒸發至剩下原有體積的一半，及冷卻至〇°c。將所形成的沈澱物過濾分離，及以冷乙醇清洗。合併後的沈澱物(3-(2-甲氧基乙氧基)-4-硝基苯基)肼（1.75克，73%)毋需進一步純化，即用於下一步驟中。 c) 在0°C，在（3-(2-曱氧基乙氧基)-4-硝基苯基)肼（1.75 克’^7.70毫莫耳）與吡啶(3.11毫升，38.5毫莫耳)於NMP(14 毫升）中之經攪拌的一溶液中，逐滴添加2,4-二氟氣碳酸苯基酯（1.631克，8.47毫莫耳）。該反應混合物於(TC攪拌20分鐘’然後在室溫中攪拌1小時。將溶液倒入1N鹽酸/冰混合物中。在攪拌30分鐘之後，添加乙酸乙酯，將有機層分離，及以1N鹽酸、水與鹽水清洗。然後將有機層乾燥（硫酸鎂）與蒸發，而留下一橘色油。藉由管柱色層分析(依序為2 :工、 1 · 1及1 . 2的石油謎/乙酸乙酯）’而得一橘色油。將該油溶於乙酸乙酯中，及以水清洗。將有機層乾燥（硫酸鎂），加以過濾與蒸發，而得一橘色泡床形式的2,4_二說苯基2-(3_(2_ 甲氧基乙氧基)-4-硝基苯基)肼羧酸酯（154克，52%)。 d) 在0°C，在2,4-二氟苯基2-(3-(2-曱氧基乙氧基)_4_硝基苯基)肼羧酸酯（1.54克，4.02毫莫耳)與吡啶（1 69〇毫升， 20.89毫莫耳）於二氣甲烷（27毫升）中之經攪拌的一溶液中，逐滴添加碳醯氯的2〇%曱苯溶液(5 〇7毫升，9 64毫莫耳）。該深紅色溶液於〇°C攪拌15分鐘，及於室溫中攪拌 97 200932732 時。添加(TC的水’將有機層分離，及依序以m鹽酸、水盘鹽水清洗。將有機層乾燥(硫酸錢），加以過濾與蒸發，而留下一紅色油。藉由管柱色層分析(依序為6: 1與4: i的石油醚/乙酸乙醋），而得—褐色固體，其自異丙醇/二氣甲烧中 5再結晶，而得—米黃色固體形式的5-(2,4-二氟笨氧基）-3-(3-(2-曱氧基乙氧基）_4•硝基苯基）13 4呋二唑 -2(3H)-酮(539毫克，33%)。 e)在室溫中，在5_(2,4_二氟笨氧基)_3_(3 (2甲氧基乙氧基)-4-硝基苯基吱二唑_2(3Η)·酮（267毫克，〇 652毫〇 10莫耳）於甲醇（18毫升）中之經攪拌的一溶液中，添加1〇%碳鈀(35毫克）。在氫氣環境下，該反應混合物於室溫中攪拌丨小時。然後讓該混合物過濾通過一矽藻土短墊，及以乙酸乙酯清洗矽藻土。將濾浪蒸發，而得一橘色油。藉由管柱色層分析（依序為4: 1與2: 1的石油峻/乙酸乙酯），而得一 15 橘色油，其在室溫中結晶。其自異丙醇/二氣甲烷中再結晶，而得一米黃色固體形式的3-(4-胺基-3-(2-甲氧基乙氧基）苯基）-5-(2,4- 一 IL 苯氧基）-1，3,4-咬二唾 _2(3Η)-酮（118 毫 ❹ 克，45%)，熔點為74-75°C。第13例： 20 K3·胺基-4-曱氣幕笨基)-5-(2,4-二氟苯氣某二岫 -2(3Η)-酮 a)在冷卻至〇°C之經劇烈攪拌的發煙硝酸(5毫升）中，分次添加5-(2,4_二氟笨氧基)-3-(4-甲氧基苯基)_ι，3,4-α夫二唾 -2(3Η)-酮1(500毫克，ι_561毫莫耳）。該黃色懸浮液於〇。匚擾 98 200932732 拌5分鐘’然後讓其回溫至室溫及攪拌3〇分鐘。將反應混合物倒入冰/水中’將所產生的沈澱物濾出，以水清洗及乾燥，而得一淡黃色固體形式的5_(2 4_二氟苯氧基)_3_(4_甲氧基-3-硝基苯基)-1,3,4-呋二唑_2(3H)_酮(533毫克，93%)。 5 b)在室溫中，在5_(2,4-二氟苯氧基)-3-(4-甲氧基-3-硝基苯基)-1，3’4-吱二唾-2(3H)-綱(520毫克，1.424毫莫耳)於甲醇 (20毫升）中之經攪拌的一懸浮液中，添加1〇%碳鈀（52毫克）。在混合物中通入氫氣2小時，及藉由過濾通過矽藻土短墊而將催化劑移除。將濾液蒸發，將所產生的淡褐色固 1〇體溶於二氣甲烷中。添加活性碳，將懸浮液攪拌15分鐘，然後過濾、通過-個石夕膠與石夕藻土短墊。將渡液蒸發，所產生的黃色固體自異丙醇中結晶，而得一橘色固體形式的 3-(3-胺基-4-甲氧基苯基)_5_(2 4_二氟苯氧基)13 4_吱二唑 -2(3H)-綱(280毫克 ’ 59%)，熔點為 1〇rc。 15 第14例：二氟苯氧皋基冬(1H-吡咯小篡、芊基)-1,3.4-诂二獅 3-(3-胺基-4·甲氧基苯基)_5_(m笨氧基)134咬二唑-2(3H)-_62毫克，〇.483毫莫耳)與2,5二甲氧基四氯 2〇 °夫喃_77毫升，〇.598毫莫耳)於乙酸(5毫升）中之經的一溶液，於霞加熱1小時，然後冷卻至室溫。在減壓下將溶劑除去，在殘餘物中添加甲笨及再次蒸發。將殘餘物溶於二氣甲燒中，及與活性碳授拌30分鐘，然後過滤通過_ 個氧化矽/矽藻土短墊。將濾液蒸發，而留下一油，其在添 99 200932732 加***之後固化。自異丙醇中再結晶，而得一淡橘色固體形式的5-(2,4-二氟苯氧基)-3-(4-甲氧基-3-(1Η-吼咯-1-基）苯基)-1,3,4-呋二唑-2(3印-酮（137毫克，73%)，熔點為136°(：。第1表顯示以一類似方式製備之其他化合物。顯示固體 5 物質的熔點。油類的NMR數據則示於第2表中。第1表名稱熔點(°C) 5-(节氧基)-3-(3-氯苯基)-1,3,4-呋二唑-2(3H)-酮 79-80 3-(4-溴苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 109-110 3-(3'-甲氧基聯苯基-4-基)-5-苯氧基-1，3,4-呋二唑-2(3扣-酮 102-103 5-(苄氧基)-3-對-曱苯基-1,3,4-呋二唑-2(3印-酮 85 5-(苄氧基)-3-(4-甲氧基苯基)-1，3,4-呋二唑-2(3H)-酮 79-80 5-(苄氧基)-3-(2-氟苯基)-1，3,4-呋二唑-2(3H)-酮 61-62 5-(苄氧基)-3-(4-氰基苯基)-1,3,4-呋二唑-2(3H)-酮 118-119 3-(4-氰基苯基)-5-苯氧基-1,3,4-呋二唑-2(3印-酮 100 5-(苄氧基)-3-(2,5-二曱基苯基)-1,3,4-呋二唑-2(3H)-酮油 5-(苄氧基)-3-(3-硝基苯基)-1，3,4-呋二唑-2(3H)-酮 108-109 3-(3-硝基苯基)-5-苯氧基-1，3,4-呋二唑-2(3H)-酮 117 3-(4-曱氧基苯基)-5-苯氧基-1，3,4-呋二唑-2(3H)-酮 75-76 5-(苄氧基)-3-苯基-1，3,4-呋二唑-2(3印-酮 86-87 3-(4-羥基苯基)-5-笨氧基-1,3,4-呋二唑-2(3H)-酮 159-160 5-苯氧基-3-苯基-1，3,4-呋二唑-2(3H)-酮 93 5-苯氧基-3-(4-(吡啶-3-基)苯基)-1,3,4-呋二唑-2(3H)-酮 146-147 3-(聯苯基-4-基)-5-苯氧基-1，3,4-呋二唑-2(3H)-酮 110-111 3-(3\4’-二曱氧基聯苯基-4-基)-5-苯氧基-1,3,4-呋二唑 -2(3H)-酮 149-150 5-(节氧基)-3-(4-特-丁基苯基)-1,3,4-呋二唑-2(3H)-酮 59 5-(节氧基)-3-(4-溴苯基)-1,3,4-呋二唑-2(3H)-酮 149-150 3-(4-溴苯基)-5-(4-硝基苯氧基)-1，3,4-呋二唑-2(3H)-酮 185-186 3-(3-氣苯基)-5-(4-硝基苯氧基)-1,3,4-呋二唑-2(3H)-酮 171-172 5-(4-氣苯氧基)-3-苯基-1,3,4-呋二唑-2(3印-酮 105-106 3-(3-溴苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 83-84 3-(聯苯基-3-基)-5-苯氧基-1,3,4-呋二唑-2(3印-酮 77-78 100 2009327323-(4-Aminophenyl)-5-(2,4-difluorophenoxy)_13,4·吱二η -2_-嗣 (203 mg, 0.665 mmol) and 2,5_2 The stirred solution of methoxytetrachloro[(0.108 ml, 0.832 mmol) in acetic acid (1 mL) was heated at 95 ° C for 1 hour to become a dark red solution. The mixture was allowed to cool to room temperature and the solvent was evaporated. Add in the residue towel and evaporate again. The residue was triturated with ethanol and washed in a hot state 2 and washed with ethanol. After drying, it is prepared - heart ~ no table, reddish brown solid 3-(4-(mt-1-yl)phenyl)-5_(2,4_difluoroindolyl)^4. Mouth 88 200932732 -2(3H)-one (109 mg '46%), melting point 181-182 °C. 8th example: 丄-(3'-methoxy kefu two peaks 2 (3 嗣嗣 under gas) in 3-(4-bromophenyl)_5-phenoxy-1,3,4_ Furadiazole 5 _2 (3 Η)·_ (526 mg, ^58 (tetra) ear), 3-methoxyphenyl (336 mg, 2.21 mmol) and potassium carbonate (567 mg, 4 1 〇 millimolar) Tetrakis(triphenylphosphine)palladium (91 mg, 0.079 mmol) was added to a stirred suspension of dimethoxyethane (20 mL) in water (1 mL). The resulting mixture was stirred at 85 ° C for 3 hours, then allowed to cool to room temperature. The solvent was removed by evaporation 10 and the residue was partitioned between hexanes and water. The organic phase was separated and washed with water and brine. Then, it is dried (magnesium sulfate) and filtered onto activated carbon. After stirring for 10 minutes, the suspension is filtered through a silicone/ground algae short sputum, and the liquid is evaporated to leave an oil after standing. Curing. Recrystallization from methylene chloride/ethanol to give 3-(3,methoxy 15-biphenyl-4-yl)-5-phenoxy-1,3,4-furadiazole as white crystals. 2(3H)-one (182 mg, 32%), melting point 1 〇 2-1 〇 3. (:. 9 cases: ^~(2,4-di-1,4-phenoxy)-3-(4-carbylbenzene, 3.2-4 2-4-2(3H)-one a) at room temperature, at 4- Methoxyphenylhydrazine hydrochloride (6 g, 34 4 mmol 2 〇) in a stirred solution of N-methyl-2-pyrrolidinone (48 ml), added dropwise to the bite ( 13.89 ml, 172 mmol), and the resulting solution was cooled to (TC. then 2,4-difluorochlorocarbonate (7-94 g, 41.2 mmol) was added dropwise. c stirring for 3 minutes, then allowed to warm to room temperature and stirred for 2 hours. The reaction mixture was poured into ice / water, and stirred for 1 89 200932732 hours. The mixture was extracted with ethyl acetate, and 2N hydrochloric acid, water and The organic extract was washed with brine and then dried (magnesium sulfate) and filtered onto activated carbon. After stirring for 15 minutes, the suspension was filtered through a short pad of silica gel and diatomaceous earth. The filtrate was evaporated to give a yellow oil. Crystallization from propanol gave 2,4-difluorophenyl 2-(4-methoxyphenyl)indolecarboxylate (3.82 g, 38%) as a white solid. b) at room temperature In 2,4-difluorophenyl 2-(4-methoxybenzene To a stirred solution of hydrazine carboxylate (3.82 g ' 12.98 mmol) in dichloromethane (120 mL), pyridine (5.46 mL, 67.5 mmol) was added dropwise and 10 The solution was cooled to (TC.) a 20% solution of carbon helium (16.39 ml '31.2 mmol) in toluene was added dropwise. The resulting orange solution was stirred at 〇 ° C for 30 minutes and then allowed to return. Warm to room temperature and stir for 1 hour. The mixture was purged with nitrogen for 3 minutes, then cooled to (TC and diluted with water. Separate the phases and wash the organic phase with 2N hydrochloric acid, water and brine, then dry (sulphate magnesium sulphate), and filter to activated carbon After stirring for 30 minutes, the suspension was filtered through a short pad of silica gel and diatomaceous earth. The filtrate was evaporated and the resulting pale yellow solid crystallized from isopropanol to give 5--2 as a white solid. , 4-difluorophenoxy)-3-(4-decyloxyphenyl)_ι, 3,4-furodioxa-2(3H)-one (1.77 g '43%). 20 c) in nitrogen Next, 5·(2,4-difluorophenoxy)-3-(4-methoxyphenyl)-1,3,4-furadiazole-2(3Η)-one (241 mg, 0.753) Milliol) A stirred solution in di-methane (5 mL) was cooled to _80. (:, and dropwise addition of boron tribromide (0.142 ml, 1.505 mmol). The solution was stirred at -80 ° C for 5 minutes, then allowed to warm to room temperature and stirred for a few hours. Then the reaction was mixed 200932732 The material was cooled to oc' and carefully quenched by the addition of water. The mixture was extracted with 30% isopropanol in methane methane, and the combined organic layers were washed with water and brine, then dried (MgSO4). Filtration and evaporation. The resulting off-white solid was crystallized from isopropyl alcohol to give 5 5 -(2,4-difluorophenoxy)-3-(4-phenylphenyl)-1 as a white solid. , 3,4-furadiazole-2(3H)-one (158 mg '69%), melting point 174.5-176X: Example 10: K4-gasocarbyl)-3-(2-fluoro-4 -Phenylphenyl)-1,3,4-° Fu 2 4_2(3!^)- Stuffed 1 a) At room temperature 'in 3-fluoro-4-wall-based benzene (5 g, 31.8 mmol) To a stirred solution of 10 acetone (100 ml), add potassium carbonate (15.40 g, 111 mmol) at a time' followed by dropwise addition of dimethyl sulphate (6 〇 4 mL, 63.7 mmol) ear). The resulting yellow suspension was stirred under reflux for 2 hours. The reaction mixture was then cooled to room temperature, dried and evaporated. The resulting yellow liquid was purified by column chromatography (9/1 petroleum ether / 15 ethyl acetate). The homogenous liquid fractions were combined and evaporated, and the resulting yellow oil was crystallized from diethyl ether/petroleum ether to give 2-fluoro- 4-methoxy-1-nitrobenzene as a pale yellow crystal (2.81 g, 52 %). b) in a solution of 2-fluoro-4-methoxy-1-nitrobenzene (2.76 g, 16.13 mmol) in methanol (5 mL) at room temperature under nitrogen , 20 Add 10% palladium (276 mg). Hydrogen was bubbled through the reaction mixture for 1 hour, and the suspension was filtered through a short pad of diatomaceous earth. The filtrate was evaporated and the resulting red oil was triturated with petroleum ether. The resulting orange solid was filtered off and dried to give 2-fluoro-4-methoxyaniline (2.2 g, 97%). c) at -10 C, in the stirred solution of 2-fluoro-4-methoxyaniline (2J3 g, 15.09 mmol) 91 200932732 in concentrated hydrochloric acid (13.97 ml) A solution of succinate (1. 121 g ' 16.25 mmol) in water (6.96 ml) while maintaining the temperature below _1 (rc). The resulting mixture was stirred at _1 (rc for 1 hour). A solution of tin (II) chloride dihydrate (2.90 ml, 3485 mM) in concentrated hydrochloric acid (11.61 ml) was added dropwise while maintaining the temperature below -5 ° C. The mixture was stirred at _rc for a few hours and then allowed to warm to room temperature. The beige suspension was filtered, the filter cake was dissolved in water, and the resulting solution was made alkaline by the addition of 3N aqueous sodium hydroxide. The mixture is then extracted with a gas, and the combined 10 extracts are washed with water and brine, dried (MgSO4), filtered and evaporated. The dark reddish brown solid is crystallized from diethyl ether/ petroleum ether. (2-Fluoro-4-methoxyphenyl)indole (1.24 g, 53%) was obtained as a dark pink solid. a solution of (2-fluoro-4-methoxyphenyl)indole (1.22 g, 7.81 mmol) in N-methyl-2-pyrrolidone (10 mL) Add pyridine (3.16 ml, 39.1 mmol) dropwise, and cool the resulting solution to 〇 ° C. Add 4-mer gas phenyl carbonate (164 〇 ml, 11.72 mmol) The solution was stirred at 0 ° C for 30 minutes, then allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was poured into ice/water and stirred for 1 hour. The precipitate was filtered and washed with water. It was dried to give 4-fluorophenyl 2-(2-fluoro-4-methoxyphenyl)indole (2.5 g, 1%) in the form of a beige solid. Wenzhong 'in 4-phenylphenyl 2-(2-fluoro-4-decyloxyphenyl) oxime acid S曰 (2.5 g ' 8.05 mmol) in ·• gas-fired (40 ml) To a solution which was dropped, pyridine (3.38 ml, 41.8 mmol) was added dropwise, and the solution of 92 200932732 produced was cooled to οι. A 20% solution of carbonium chloride in toluene (1 〇 16 ml I 19.1 mmol) was then added dropwise. The resulting red suspension was stirred at 〇〇c for 30 minutes' then allowed to warm to room temperature and stirred for a few hours. Nitrogen gas was bubbled through the mixture for 30 minutes before cooling to and diluted with water. The phases were separated and the organic phase was washed with 2N hydrochloric acid, water and brine. The organic layer was dried (MgSO.sub.4), filtered and evaporated and evaporated. Allow the suspension to filter through a short pad of tannin and Shixia. The filtrate was evaporated, and the resulting yellow solid was crystallised twice from isopropyl alcohol to give 5-(4-chlorophenoxy)_3_(2-fluoro-4-methoxybenzene as a beige solid. Base), 3,4-furadiazole-2(3H)-one (1.2 g, 44%). 5〇〇(5-chlorophenoxy)-3-(2-fluoro-4-methoxyphenyl)-1,3,4-furadiazole-2(3Η)-one under nitrogen (1.2 g, 3.56 mmol) of a stirred solution in dichloromethane (40 ml) was cooled to _8 〇 <t, and boron tribromide (0.674 ml, 7.13 mmol) was added dropwise. ear). The solution was stirred at _8 (η: for 5 minutes, then allowed to warm to room temperature and swim for 5 hours. The reaction mixture 15 was then cooled to ot and carefully quenched by the addition of water. Add 3 % difference The mixture was separated from the mixture of propanol in a gas chamber. The aqueous phase was extracted with di-methane, and the combined extracts were washed with water and brine. The organic layer was dried (MgSO4), filtered and evaporated. The resulting green solid is dissolved in hot isopropanol and the insoluble material is filtered off. The filtrate is evaporated and the residue crystallised from dichloro[rho]*methane/ petroleum ether to give a dark solid. Dissolved in di-methane and added with activated carbon. After 15 minutes of stirring, the suspension was filtered through a short pad of silica gel and diatomaceous earth. The filtrate was evaporated to a small volume and PE was added. Filtration, washing with petroleum ether and drying to give 5 (4 chloro oxo 93 200932732 yl)-3-(2-fluoro-4-pyridylphenyl)], 3,4 吱 as an off-white solid Disporin-2 (3H) ketone (10 mg, 33%), melting point 180-182 ° C. The eleventh case: 3-(4-amine U dimethyl benzophenone difluoromethane 氲Vl a 』 - 口夫二0 sit 5 -2 (3H)-ketone hydrochloride a) at room temperature In a suspension of 5-fluoro-2.nitrophenylhydrazine (1 g, 63 7 mmol) and potassium carbonate d7·59 g 'm mmol) in acetone (10 ml) Methyl iodide (1194 ml, 191 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 4 days, then evaporated under reduced pressure to remove <RTI ID=0.0>> The aqueous layer was neutralized with concentrated hydrochloric acid. Separating the organic layer 'washed with water and brine, dried (sulfur secret) - and transitioned and evaporated to give an off-white solid, which was recrystallized from isopropanol / dioxin @ to give an off-white solid 4_Gas_2_methoxy succinylbenzene (9.6 g, 88%). 15 b) Add a solution of hydrazine hydrate (5.96 ml) in a solution of '412-methoxy small nitrobenzene σg, 40.9 mmoles in ethanol (84 ml) at room temperature. , 123 millimoles). The solution turns yellow and then turns bright 〇 orange. The reaction mixture was stirred at loot for 2 hours and then cooled to 〇t. The yellow precipitate was separated by filtration and washed with cold ethanol. The mother liquor is evaporated to 2 〇 leaving half the volume' and then cooled to 〇t to form more swells. The precipitate was collected and washed with cold ethanol. The precipitate was combined to give (3methoxy_4_nitrophenyl) oxime (4.18 g, 56%). c) at 0C 'in (3-methoxy-4-decyl) ploughing (4 g, 2184 mmol) with acridine (8.83 ml, 109 mmol) in NMp (4 mL) 2,4-difluorocarbon carbonate stupid vinegar (4.63 g, 24.02 mmol) was added dropwise to the two liquids of 200932732. The reaction mixture was in hydrazine. 〇 Mix for 15 minutes and then mix for 45 minutes at room temperature. The solution was then poured into a mixture of ice/1N hydrochloric acid solution. The product was extracted sequentially with ethyl acetate, dioxane/isopropanol. The combined organic layers were washed with 5 brine, and the mixture was evaporated and evaporated. An orange oil/solid form of 2,4-difluorophenyl 2-(2) was obtained by column chromatography (Oxidized Oxide, in the order of 2:1 and 1:1 petroleum-acetic acid). 3-decyloxy-4-nitrophenyl)indolecarboxylate (5 84 g, 79%). d) at 0C, in 2,4-difluorophenyl 2-(3-methoxy-4-phenyl-phenyl)indole carboxylate (5.84 g, 17.21 mmol) with pyridine (7.24 ml) A 90% solution of carbon helium in toluene (21.74 mL, 41.3 mmol) was added dropwise to a stirred solution of dioxane (115 mL). The solution turned dark red, stirred at 〇 ° C for 15 minutes and then at room temperature for 45 minutes. Air was introduced into the valley solution for 10 minutes, and then water of 〇 ° C was added. The organic layer was separated, washed successively with 1N hydrochloric acid, water and brine, then dried (MgSO4) and filtered and evaporated to give a dark red oil "by column chromatography (2: 1 and 1 : 1 of petroleum sulphur / dichloro decane) gave a yellow solid which was recrystallized from isopropanol / di- methane to give 5 (2,4 - difluoro phenyloxy) _3 ( 3Methoxy-4-nitrophenyl)-1,3,4-furodisin-2(3H)-_(722 mg, 11.5%). 2〇e) at room temperature in 5-(2,4-difluorophenoxy)-3-(3-methoxy-4-nitrophenyl)-1,3,4-furadiazole To a stirred solution of -2(3H)-one (200 mg, 0.548 mmol) in MeOH (methanol), EtOAc (EtOAc) The reaction mixture was stirred at room temperature for 3 hours under a hydrogen atmosphere. An additional 10% palladium on carbon catalyst (9 mg) was added and the reaction mixture was stirred for a further 2 hours under hydrogen at 95 200932732. The solution was then filtered through a short pad of Shixiazao and the diatomaceous earth was washed with ethyl acetate. The filtrate was evaporated to give a brown solid which crystallised from EtOAc. This was dissolved in ethyl acetate (5 mL) and cooled to EtOAc (EtOAc) The precipitate formed was filtered, washed with ethyl acetate and dried to give 3-(4-amino-3-methoxyphenyl)-5-(2,4-di. Fluorophenoxy)-1,3,4-furadiazole-2(311)--hydrochloride (120 mg, 90%), m.p. 186-188. (:. 12th case: ❹ 10 K4-Amino-3-(2·A nitrogen, a certain ethylene) Laughing 1 V5-(2,4·II I stupid ^J-1,3,4-bite two Salivation-2 (3HV ketone a) at room temperature in 5-fluoro-2-nitrophenol (4 g, 25.5 mmol), potassium carbonate (10.56 g, 76 mmol) and 1-chloro-2 To a stirred suspension of 15 in MeOH (5 mL) (5.10 mL, 56.0 mmol), sodium iodide (0·191 g, 1.273 mmol) was added. The mixture was stirred at 8 ° C overnight. Then add 1- gas-2-methoxyethane (6.38 ml, 70.0 mmol) and the reaction mixture was stirred at 80 ° C for 4 hours. Add water and B @ Ethyl acetate, the organic layer was separated, the aqueous layer was neutralized with 1N hydrochloric acid, and extracted with ethyl acetate. The combined organic layer was washed with water, dried (MgSO4) and filtered and evaporated. Oil. By column chromatography (6: i petroleum ether / ethyl acetate), 4_fluoro-2_(2methoxyethoxy M-nitrobenzene (2.26g) was obtained as a clear oil. , 39%) b) at room temperature in 4-fluoro-2-(2-methoxyethoxy)- nitrobenzene (2.26 g '10.50 mmol) in ethanol (21. Stirred solution in 43 ml) 96 200932732 5 e 10 15 ❹ 20 Add hydrazine hydrate (1.531 ml '3·5 mmol) in the solution. The reaction mixture was stirred at 85 ° C for 3 hours. Cool to 〇 ° C ' and form a precipitate. The solid is separated by filtration and washed with cold ethanol. The mother liquid is evaporated to half of the original volume, and cooled to 〇 ° C. The precipitate formed Separated by filtration and washed with cold ethanol. The combined precipitate (3-(2-methoxyethoxy)-4-nitrophenyl)indole (1.75 g, 73%) was purified further. In the next step, c) at 0 ° C, in (3-(2-decyloxyethoxy)-4-nitrophenyl)indole (1.75 g '^7.70 mmol) with pyridine (3.11) 2,4-difluorocarbonic acid phenyl ester (1.631 g, 8.47 mmol) was added dropwise to a stirred solution of NMP (14 mL). (TC was stirred for 20 minutes' and then stirred at room temperature for 1 hour. The solution was poured into a 1 N hydrochloric acid/ice mixture. After stirring for 30 minutes, ethyl acetate was added and the organic layer was separated. The organic layer was dried (MgSO.sub.4) and evaporated to leave an orange oil. 2 oil mystery / ethyl acetate)' obtained an orange oil. The oil was dissolved in ethyl acetate and washed with water. The organic layer was dried (MgSO4), filtered and evaporated to give an orange 2,4_bis phenyl 2-(3-(2-methoxyethoxy)-4-nitrophenyl)indolecarboxylate (154 g, 52%) in the form of a color bubble. d) 2,4-Difluorophenyl 2-(3-(2-decyloxyethoxy)_4_nitrophenyl)indolecarboxylate (1.54 g, 4.02 mmol) at 0 °C To a stirred solution of pyridine (1 69 mM, 20.89 mmol) in di-methane (27 mL), a solution of 2 〇曱曱 benzene (5 〇 7 mL, 9 64 millimoles). The dark red solution was stirred at 〇 ° C for 15 minutes and at room temperature for 97 200932732. Add (water of TC) to separate the organic layer, and sequentially wash with m hydrochloric acid, water tray brine. Dry the organic layer (sulfate), filter and evaporate, leaving a red oil. Analysis (6: 1 and 4: i petroleum ether / ethyl acetate), and obtained a brown solid, which was recrystallized from isopropanol / gas aeration, and obtained as a beige solid. 5-(2,4-Difluoro phenyloxy)-3-(3-(2-decyloxyethoxy)-4 nitrophenyl) 13 4 furadiazole-2(3H)-one (539 Mg, 33%) e) 5_(2,4-difluorooctyloxy)_3_(3(2methoxyethoxy)-4-nitrophenyloxadiazole_2 at room temperature (3 Η)· Ketone (267 mg, 〇 652 〇 10 mM) in a stirred solution of methanol (18 mL), 1% by weight of palladium (35 mg) was added. The mixture was stirred at room temperature for a few hours, then the mixture was filtered through a short pad of diatomaceous earth and the celite was washed with ethyl acetate. The filtrate was evaporated to give an orange oil. Analysis (in order of 4: 1 and 2: 1 for the oil/ethyl acetate), and get a 15 orange Oil, which crystallizes at room temperature. It is recrystallized from isopropanol/di-methane to give 3-(4-amino-3-(2-methoxyethoxy) as a beige solid. Phenyl)-5-(2,4-mono-l-phenoxy)-1,3,4-didentate di-salt-2(3Η)-one (118 mM, 45%), melting point 74-75° C. 13th case: 20 K3·Amino-4-曱 gas curtain stupid base)-5-(2,4-Difluorobenzene gas a certain diterpene-2(3Η)-ketone a) is cooled to 〇°C 5-(2,4-difluorooctyloxy)-3-(4-methoxyphenyl)_ι, 3,4-α夫 was added in portions with vigorously stirred fuming nitric acid (5 ml). Disporin-2(3Η)-one 1 (500 mg, ι_561 mmol). The yellow suspension is in the mash. Breathing 98 200932732 Mix for 5 minutes' then let it warm to room temperature and stir for 3 minutes. The reaction mixture was poured into ice/water. The resulting precipitate was filtered, washed with water and dried to give 5-(2-difluorophenoxy)_3_(4-methoxy) as a pale yellow solid. 3-Nitrophenyl)-1,3,4-furadiazole-2(3H)-one (533 mg, 93%). 5 b) at room temperature in 5-(2,4-difluorophenoxy)-3-(4-methoxy-3-nitrophenyl)-1,3'4-indenyl disani-2 (3H)-- (520 mg, 1.424 mmol) in a stirred suspension of methanol (20 mL), EtOAc (EtOAc) Hydrogen was bubbled through the mixture for 2 hours and the catalyst was removed by filtration through a short pad of diatomaceous earth. The filtrate was evaporated and the resulting pale brown solid was dissolved in di-methane. Activated carbon was added, the suspension was stirred for 15 minutes, then filtered, passed through a short mat of Shishijiao and Shixiazao. The ferric liquid was evaporated, and the resulting yellow solid was crystallized from isopropyl alcohol to give 3-(3-amino-4-methoxyphenyl)-5-(2 4 -difluorophenoxy) as an orange solid. Base) 13 4 oxadiazole-2 (3H)-class (280 mg '59%), melting point 1 〇 rc. 15 14th example: difluorophenoxypurinyl winter (1H-pyrrole, fluorenyl)-1,3.4-诂 two lion 3-(3-amino-4.methoxyphenyl)_5_(m stupid Oxyl) 134 oxadiazole-2 (3H)--62 mg, 〇.483 mmoles with 2,5 dimethoxytetrachloro 2 〇 ° 喃 _ _77 ml, 〇. 598 mM) A solution of acetic acid (5 ml) was heated in Xishui for 1 hour and then cooled to room temperature. The solvent was removed under reduced pressure, and the residue was added and evaporated again. The residue was dissolved in a methane, and mixed with activated carbon for 30 minutes, and then filtered through a short pad of cerium oxide/diatomaceous earth. The filtrate was evaporated to leave an oil which solidified after the addition of diethyl ether. Recrystallization from isopropanol gave 5-(2,4-difluorophenoxy)-3-(4-methoxy-3-(1Η-吼-r--1-) as a pale orange solid Phenyl)-1,3,4-furadiazole-2 (3 - ketone (137 mg, 73%), melting point 136 ° (:. Table 1 shows other compounds prepared in a similar manner. The melting point of the solid 5 substance is shown. The NMR data of the oil are shown in Table 2. The first table name melting point (°C) 5-(oxy group)-3-(3-chlorophenyl)-1,3 , 4-furadiazole-2(3H)-one 79-80 3-(4-bromophenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 109- 110 3-(3'-Methoxybiphenyl-4-yl)-5-phenoxy-1,3,4-furadiazole-2 (3-butanone 102-103 5-(benzyloxy) )-3-p-phenyl-p-phenyl-1,3,4-furadiazole-2 (3-indolyl 85 5-(benzyloxy)-3-(4-methoxyphenyl)-1,3 , 4-furadiazole-2(3H)-one 79-80 5-(benzyloxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 61-62 5-(Benzyloxy)-3-(4-cyanophenyl)-1,3,4-furadiazole-2(3H)-one 118-119 3-(4-cyanophenyl) -5-phenoxy-1,3,4-furadiazole-2 (3-ink-one 100 5-(benzyloxy)-3-(2,5-didecylphenyl)-1,3 , 4-furadiazole-2(3H)-one oil 5-(benzyloxy)-3-(3-nitrophenyl)-1 ,3,4-furadiazole-2(3H)-one 108-109 3-(3-nitrophenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)- Ketone 117 3-(4-decyloxyphenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 75-76 5-(benzyloxy)-3-benzene Base-1,3,4-furadiazole-2 (3-acetone 86-87 3-(4-hydroxyphenyl)-5-indolyl-1,3,4-furadiazole-2 (3H )-ketone 159-160 5-phenoxy-3-phenyl-1,3,4-furadiazole-2(3H)-one 93 5-phenoxy-3-(4-(pyridine-3- Phenyl)-1,3,4-furadiazole-2(3H)-one 146-147 3-(biphenyl-4-yl)-5-phenoxy-1,3,4-furan Diazole-2(3H)-one 110-111 3-(3\4'-dimethoxyoxybiphenyl-4-yl)-5-phenoxy-1,3,4-furadiazole-2 (3H)-ketone 149-150 5-(hydroxy)-3-(4-tert-butylphenyl)-1,3,4-furadiazole-2(3H)-one 59 5-(section) Oxy)-3-(4-bromophenyl)-1,3,4-furadiazole-2(3H)-one 149-150 3-(4-bromophenyl)-5-(4-nitro Phenoxy)-1,3,4-furadiazole-2(3H)-one 185-186 3-(3-phenylphenyl)-5-(4-nitrophenoxy)-1,3, 4-furadiazole-2(3H)-one 171-172 5-(4-phenoxy)-3-phenyl-1,3,4-furadiazole-2 (3-acetone 105-106 3-(3-bromophenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 83-84 3-(biphenyl-3-yl) )-5-phenoxy-1,3,4-furadiazole-2 (3 - ketone 77-78 100 200932732

5-苯氧基-3-(3-(°比啶-3-基)苯基)-1，3,4-呋二唑-2(3H)-酮 81-82 5-(4-甲氧基苯氧基)-3-苯基-1,3,4-呋二唑-2(3H)-酮 61-62 5-(苄氧基)-3-(3-溴苯基)-1,3,4-呋二唑-2(3H)-酮 89-90 5-(4-(节氧基)苯氧基)-3-苯基-1,3,4-呋二唑-2(3H)-酮 99-100 3-(5’-曱氧基聯苯基-3-基)-5-苯氧基-1，3,4-呋二唑-2(311)-酮 69-70 5-(4-羥基苯氧基)-3-苯基-1，3,4-呋二唑-2(3H)-酮 176-177 5-(苄氧基)-3-(聯苯基-3-基)-1,3,4-呋二唑-2(311)-酮 74-75 5-(节氧基)-3-(3'-甲氧基聯苯基-3-基)-1,3,4-呋二唑-2(3H)-酮 82-83 5-(4-氣苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 75-76 3-(4'-氰基聯苯基-3-基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 116-117 3-(2-氟苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 60-61 3-(3’-氰基聯苯基-3-基)-5-苯氧基-1，3,4-呋二唑-2(3印-酮 109-110 3-(4'-氰基聯苯基-4-基)-5-苯氧基-1,3,4-呋二唑-2(3印-酮 171-172 5-(4-氣苯氧基)-3-(2,4-二氟苯基)-1,3,4-呋二唑-2(311)-酮 116-117 5-(节氧基)-3-(2,5-二氟苯基)-1,3,4-呋二唑-2(3H)-酮 74-75 3-(2,5-二氟苯基)-5-苯氧基-1，3,4-呋二唑-2(3H)-酮 109-110 3-(2-氟苯基)-5-(4-曱氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮油 5-(苄氧基)-3-(2,4-二氟苯基)-1，3,4-呋二唑-2(3H)-酮 89-90 3-(2-氟苯基)-5-(4-硝基苯氧基)-1，3,4-呋二唑-2(3H)-酮 110-111 5-(4-氣苯氧基)-3-(2,5-二氟苯基)-1,3,4-呋二唑-2(3H)-酮 129-130 5-(4-氯苯氧基)-3-(3'，4’-二甲氧基聯苯基-3-基)-1，3,4-咬二嗤 -2(3H)-酮 146-147 3-(3-溴苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑-2(3H)-酮 98-99 3-(2,4-二氟苯基)-5-苯氧基-1，3,4-呋二唑-2(3H)-酮 49-50 3-(2,4-二氟苯基)-5-(萘-1-基氧)-1，3,4-呋二唑-2(3H)-酮 119-120 5_(2_氣苯氧基)-3-(2-氟苯基)-1，3,4-呋二唑-2(3H)-酮 61-62 3-(2,4-二氟苯基)-5-(3-(三氟曱基）苯氧基)-1，3,4-呋二唑 -2(3H)-酮油 5-(4-溴苯氧基)-3-(2,5-二氟苯基)-1,3,4-呋二唑-2(3H)-酮 130-131 3-(2,5-二氟苯基)-5-(4-氟苯氧基)-1,3,4-呋二唑-2(3H)-酮 93-94 5-(苄氧基)-3-(2-曱氧基苯基)-1,3,4-呋二峻-2(3H)-酮 98-99 3-(2-甲氧基苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 121-122 5-(4-氣苯氧基)-3-(2-曱氧基苯基)-1,3,4-呋二唑-2(3H)-酮 85-86 5-(4-氟苯氧基)-3-(2-曱氧基苯基)-1,3,4-呋二唑-2(3H)-酮 96-97 3-(2-氣苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮油 139-140 3-(4-溴苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑-2(3H)-酮 200932732 5-(4-氣苯氧基)-3-(4'-氰基聯苯基-3-基)-1,3,4-呋二嗤-2(3印-酮 191-192 5-(2,4-二氟苯氧基)-3-苯基-1，3,4-呋二唑-2(3H)-酮 76-77 3-(3-氣苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑-2(3H)-酮 81-82 5-(2,4-二氟苯氧基)-3-(4-曱氧基苯基)-1,3,4-呋二唑-2(3H)-_ 90-91 5-(4-氣苯氧基)-3-(3’,4'-二甲氧基聯苯基-4-基)-1,3,4-呋二唑 -2(3H)-酮 156-157 3-(5-溴-2-氟苯基)-5-(4-甲氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 69-70 3-(4-氟-4’,5’-二甲氧基聯苯基-3-基)-5-(4-曱氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 111-112 3-(3-溴笨基)-5-(4-曱氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 101-102 3-(4-溴苯基)-5-(4-曱氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 90-91 3-(4-氟苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 90-91 5-(4-氣苯氧基)-3-(4-氟-4’,5’-二甲氧基聯苯基-3-基)-1,3,4-呋二唑-2(3H)-酮 137-138 3-(2-氟-4-(吼啶-3-基)苯基)-5-(4-曱氧基苯氧基)-1,3,4-呋二 140-141 3-(3-氟-4’，5’-二甲氧基聯苯基-4-基)-5-(4-曱氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 96-97 3-(3-氣-4’-氣基聯苯基-4-基)-5-(4-曱氧基苯乳基)-1，3,4-咬二 °坐-2(311)-嗣 132-133 3-(4-氟苯基)-5-(4-曱氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 108-109 3-(4-氣-2-氟苯基)-5-(4-曱氧基苯氧基)-1，3,4-呋二唑-2(3H)-嗣 89-90 5-(4-曱氧基苯氧基)-3-(4-甲氧基苯基)-1，3,4-呋二唑-2(3H)-酮 100-101.5 5-(4-氣苯氧基)-3-(4-甲氧基苯基)-1,3,4-呋二唑-2(3H)-酮 98-99 3-(4·-(二甲基胺基)-3-氣聯苯基-4-基)-5-(4-甲乳基苯氣基)-1,3,4-呋二唑-2(3H)-酮 160-161 5-(4-氣苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 146-147 3-(4-溴苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑-2(3H)-酮 114-115 5-(4-溴-2-曱氧基苯氧基)-3-苯基-1,3,4-呋二唑-2(3H)-酮 77-78 5-(3,5-二曱氧基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-闕 97-98 5-(4-氰基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 125-126 3-(2-氟苯基)-5-(萘-2-基氧)-1,3,4-呋二唑-2(311)-酮 101-102 3-苯基-5-(吡啶-3-基氧)-1,3,4-呋二唑-2(311)-酮 88-89 3-(4-(1Η-四唑-5-基)苯基)-5-笨氧基-1，3,4-呋二唑-2(3H)-酮 201-202 3-(5-溴-2-氟苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑-2(3H)-酮 107-108 5-(4-氟苯氧基)-3-(4-羥基苯基)-1，3,4-呋二唑-2(3H)-酮 155-156 5-(4-( 1H-四唑-5-基）苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑 -2(3H)-酮 153-154 5-(3,4-二曱氧基苯氧基)-3-(2-氟苯基)-1，3,4-呋二唑-2(3H)-酮 82.5-83 5-(2,4-二氟苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 174-175 3-(2-氟-4-(甲基磺醯基)苯基)-5-(4-曱氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 95-96 200932732 5-(4-氟苯氧基)-3-(4-甲氧基苯基)-1,3,4-呋二唑-2(3H)-酮 89-90 5-(聯苯基-4-基氧)-3-(2-氟苯基)-l，3,4-呋二唑-2(3H)-酮 81-81 3-(2-氟苯基)-5-(3,4,5-三甲氧基苯氧基)-1,3,4-呋二唑 -2(3H)_ 酮 139-140 3-(4-曱氧墓苯基)-5-(3-(三氟甲基）苯氧基)-1，3,4-咬二唑 -2(3H)-酮 70-71 3-(4-甲氧基苯基)-5-(對-甲苯基氧)-1,3,4-呋二唑-2(3H)-酮 83-84 3-(4-羥基苯基)-5-(對-甲苯基氧)-1,3,4-呋二唑-2(3H)-酮 159-160 3-(3-氣-2-氟苯基)-5-(4-甲氧基苯氧基)-1,3,4-呋二唑-2(3H)-_ 102-103 3-(4-羥基苯基)-5-(3-(三氟曱基）苯氧基)-1,3,4-呋二唑 -2(3H)-酮 167-168 5-(节氧基)-3-(3-氟苯基)-1，3,4-呋二唑-2(3H)-酮 101-102 3-(3-氟苯基)-5-(4-甲氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 84-85 5-(3,5-二羥基苯氧基)-3-(2-氟笨基)-1,3,4-呋二唑-2(3H)-酮 155-156 3-(4-甲氧基苯基)-5-(吡啶-3-基氧)-1,3,4-呋二唑-2(3H)-酮 79-80 5-(2-氣-4-羥基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 122-123 3-(5-氣-2-氟苯基)-5-(4-甲氧基苯氧基)-1，3,4-呋二峻-2(3H)-_ 85-86 3-(4-羥基苯基)-5-(4-硝基苯氧基)-1,3,4-呋二唑-2(3H)-酮 174-175 5-(2,4-二氣苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 177-178 3-(2-氟苯基)-5-(3-羥基苯氧基)-1,3,4-呋二唑-2(3H)-酮 140-141 3-(2-氟苯基)-5-(吼啶-3-基氧)-1,3,4-呋二唑-2(3H)-酮 63-64 3-(2,4-二氟苯基)-5-(吡啶-3-基氧)-1,3,4-呋二唑-2(3H)-酮 89-90 3-(2-氟-4-(甲基磺醯基)苯基)-5-(吼啶-3-基氧)-1,3,4-呋二唑 -2(3H)-酮 100-100 5-(2-溴吡啶-3-基氧)-3-(4-甲氧基苯基)-1,3,4-呋二唑-2(3H)-酮 116-117 5-(2,4-二-特-丁基苯氧基)-3-(2-氟苯基)-1,3,4-咬二°坐 -2(3H)-酮油 5-(環己氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 58-59 5-(2,6-二甲基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 88-89 3-(3-氣-2-氟苯基)-5-(環己氧基)-1，3,4-呋二唑-2(3H)-酮 84-85 5-(環己氧基)-3-(4-甲氧基苯基)-1,3,4-呋二唑-2(3H)-酮 71-72 3-(2,4-二氟苯基)-5-(2,6-二甲氧基苯氧基)-1,3,4-吱二唑 -2(3H)-酮 94-95 己乳基)-3-(3-氣_4'，5'_二曱乳基聯苯基-4-基)-1，3,4-咬二 σ坐-2(3H)-嗣 101-102 3-(3-羥基苯基)-5-苯氧基-1,3,4-呋二唑-2(311)-酮 116-117 5-(環己氧基)-3-(3-氟-3’-(三氟甲氧基)聯苯基-4-基)-1,3,4-呋二唑-2(3H)-酮 91-92 5-(4-氣苯氧基)-3-(3-羥基苯基)-1，3,4-呋二唑-2(3H)-酮 166-167 5-(4-氟苯氧基)-3-(3-羥基苯基)-1,3,4-呋二唑-2(3印-酮 163-164 3-(4-亂-2-氣苯基)-5-苯乙氧基-1，3,4-咬二°坐-2(311)-明 52-53 103 200932732 3-(4-羥基苯基)-5-苯乙氧基-1,3,4-呋二唑-2(3H)-酮 148-149 3-(2-氟苯基)-5-異丁氧基-1,3,4-呋二唑-2(3H)-酮油 3-(4-羥基苯基)-5-(3-苯基丙氧基)-1,3,4-呋二唑-2(3H)-酮 129-130 3-(4-羥基苯基)-5-(4-苯基丁氧基)-1,3,4-呋二唑-2(3H)-酮 120-121 3-(4-羥基苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑-2(3H)-酮 128-128 3-(4-羥基苯基)-5-(6-苯基己基氧)-1,3,4-呋二唑-2(3H)-酮 107-108 3-(4-胺基項醯基苯基)-5-(4-氟苯氧基)-1,3,4-呋二唑-2(3H)-酮 217-218 3-(4-胺基磺酿基苯基)-5-(4-曱氧基苯氧基)-1，3,4-呋二唑 -2(3H)-酮 191-192 3-(4-羥基苯基)-5-(2-苯氧基乙氧基)-l，3/l·呋二唑-2(3H)-酮 164-165 5-(2-氣苯乙氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 139-140 3-(4-胺基績醯基苯基)-5-(4-氣苯氧基)-1，3,4-呋二唑-2(3H)-酮 227-228 3-(4-胺基磺醯基苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 204-205 3-苯基-5-(5-苯基戊基氧)-1,3,4-呋二唑-2(3H)-酮 50-51 3-(2-氟苯基)-5-(4-苯基丁氧基)-1,3,4-呋二唑-2(3H)-酮油 3-(4-胺基磺醯基苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑 -2(3H)-酮 143-144 3-(2-氟苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑-2(3H)-酮油 3-(2,4-二氟苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑-2(3H)-酮 40-41 5-(4-(3,4-二甲氧基苯基）丁氧基)-3-苯基-1,3,4-呋二唑 -2(3H)-酮 56-57 3-(2-氣-5-氟苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑-2(3H)-酮油 5-(4-(3,4-二甲氧基苯基)丁氧基)-3-(2-氟苯基)-1,3,4-呋二唑 -2(3H)-酮油 5-(2-氣苯乙氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 79-80 3-(2,4-二氟苯基)-5-(4-(3,4-二曱氧基苯基)丁氧基)-1,3,4-呋二唑-2(3H)-酮油 3-(4-氣-2-氟苯基)-5-(4-(3,4-二甲氧基苯基)丁氧基)-1，3,4-呋二 σ坐-2(3H)-嗣油 3-(3-氣-2-氟苯基)-5-(4-(3,4-二甲氧基苯基)丁氧基)-1，3,4-呋二吐-2(3H)-嗣油 3-(4-胺基羰基苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 226-227 3-(4-胺基磺醯基苯基)-5-(4-(3,4-二曱氧基苯基）丁氧基)-1，3,4-呋二唑-2(3H)-酮 148-149 3-(2-氟苯基)-5-(4-(4-氟苯基)丁氧基)-1,3,4-呋二唑-2(3H)-酮油 3-(4-胺基羰基苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑-2(3H)-酮 240-241 3-(4-胺基羰基苯基)-5-(4-甲氧基苯氧基)-1,3,4-呋二唑 -2(3H)-酮 190-191 3-(4-胺基羰基苯基)-5-(4-(4-氟笨基）丁氧基)-1,3,4-呋二唑 -2(3H)-酮 142-142 3-(4-胺基羰基苯基)-5-(5-(4-氟苯基）戊基氧)-1,3,4-呋二唑 -2(3H)-酮 155-156 3-(4-胺基羰基苯基)-5-(4-對-甲苯基丁氧基)-1,3,4-呋二唑 -2(3H)-酮 154-155 2009327325-phenoxy-3-(3-(pyridin-3-yl)phenyl)-1,3,4-furadiazole-2(3H)-one 81-82 5-(4-methoxy Phenyloxy)-3-phenyl-1,3,4-furadiazole-2(3H)-one 61-62 5-(benzyloxy)-3-(3-bromophenyl)-1, 3,4-furadiazole-2(3H)-one 89-90 5-(4-(hydroxy)phenoxy)-3-phenyl-1,3,4-furadiazole-2 (3H )-keto 99-100 3-(5'-nonyloxybiphenyl-3-yl)-5-phenoxy-1,3,4-furadiazole-2(311)-one 69-70 5 -(4-hydroxyphenoxy)-3-phenyl-1,3,4-furadiazole-2(3H)-one 176-177 5-(benzyloxy)-3-(biphenyl-3 -yl)-1,3,4-furadiazole-2(311)-ketone 74-75 5-(hydroxy)-3-(3'-methoxybiphenyl-3-yl)-1 ,3,4-furadiazole-2(3H)-one 82-83 5-(4-phenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2 (3H)-keto 75-76 3-(4'-Cyanobiphenyl-3-yl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 116-117 3-(2-fluorophenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 60-61 3-(3'-cyanobiphenyl-3-yl -5-phenoxy-1,3,4-furadiazole-2 (3-ink-ketone 109-110 3-(4'-cyanobiphenyl-4-yl)-5-phenoxy- 1,3,4-furadiazole-2 (3 - ketone 171-172 5-(4-phenoxy)-3-(2,4-difluorophenyl)-1,3,4-furan Diazole-2 (311)- 116-117 5-(Hydroxy)-3-(2,5-difluorophenyl)-1,3,4-furadiazole-2(3H)-one 74-75 3-(2,5- Difluorophenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 109-110 3-(2-fluorophenyl)-5-(4-decyloxybenzene Oxy)-1,3,4-furadiazole-2(3H)-one oil 5-(benzyloxy)-3-(2,4-difluorophenyl)-1,3,4-furo Azole-2(3H)-one 89-90 3-(2-fluorophenyl)-5-(4-nitrophenoxy)-1,3,4-furadiazole-2(3H)-one 110 -111 5-(4-Vephenoxy)-3-(2,5-difluorophenyl)-1,3,4-furadiazole-2(3H)-one 129-130 5-(4- Chlorophenoxy)-3-(3',4'-dimethoxybiphenyl-3-yl)-1,3,4-dioxadi-2(3H)-one 146-147 3-( 3-bromophenyl)-5-(4-aphenoxy)-1,3,4-furadiazole-2(3H)-one 98-99 3-(2,4-difluorophenyl)- 5-phenoxy-1,3,4-furadiazole-2(3H)-one 49-50 3-(2,4-difluorophenyl)-5-(naphthalen-1-yloxy)-1 , 3,4-furadiazole-2(3H)-one 119-120 5_(2_gasphenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2 ( 3H)-keto 61-62 3-(2,4-difluorophenyl)-5-(3-(trifluoromethyl)phenoxy)-1,3,4-furadiazole-2 (3H) -ketone oil 5-(4-bromophenoxy)-3-(2,5-difluorophenyl)-1,3,4-furadiazole-2(3H)-one 130-131 3-(2 , 5-difluorobenzene 5-(4-fluorophenoxy)-1,3,4-furadiazole-2(3H)-one 93-94 5-(benzyloxy)-3-(2-decyloxybenzene -1,3,4-furodis-2(3H)-one 98-99 3-(2-methoxyphenyl)-5-phenoxy-1,3,4-furadiazole- 2(3H)-ketone 121-122 5-(4-Vephenoxy)-3-(2-decyloxyphenyl)-1,3,4-furadiazole-2(3H)-one 85- 86 5-(4-Fluorophenoxy)-3-(2-decyloxyphenyl)-1,3,4-furadiazole-2(3H)-one 96-97 3-(2-benzene 5-(phenoxy-1,3,4-furadiazole-2(3H)-one oil 139-140 3-(4-bromophenyl)-5-(4-phenoxy)- 1,3,4-furadiazole-2(3H)-one 200932732 5-(4-Vephenoxy)-3-(4'-cyanobiphenyl-3-yl)-1,3,4 -furodiindole-2 (3 - ketone 191-122 5-(2,4-difluorophenoxy)-3-phenyl-1,3,4-furadiazole-2(3H)-one 76 -77 3-(3-Phenylphenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2(3H)-one 81-82 5-(2, 4-Difluorophenoxy)-3-(4-decyloxyphenyl)-1,3,4-furadiazole-2(3H)-_ 90-91 5-(4-phenoxy) -3-(3',4'-dimethoxybiphenyl-4-yl)-1,3,4-furadiazole-2(3H)-one 156-157 3-(5-bromo-2 -fluorophenyl)-5-(4-methoxyphenoxy)-1,3,4-furadiazole-2(3H)-one 69-70 3-(4-fluoro-4',5' -dimethoxybiphenyl-3 -yl)-5-(4-decyloxyphenoxy)-1,3,4-furadiazole-2(3H)-one 111-112 3-(3-bromophenyl)-5-(4 -decyloxyphenoxy)-1,3,4-furadiazole-2(3H)-one 101-102 3-(4-bromophenyl)-5-(4-decyloxyphenoxy) -1,3,4-furadiazole-2(3H)-one 90-91 3-(4-fluorophenyl)-5-phenoxy-1,3,4-furadiazole-2 (3H) -ketone 90-91 5-(4-Vephenoxy)-3-(4-fluoro-4',5'-dimethoxybiphenyl-3-yl)-1,3,4-furo Oxazole-2(3H)-one 137-138 3-(2-fluoro-4-(acridin-3-yl)phenyl)-5-(4-decyloxyphenoxy)-1,3,4 -furan 140-141 3-(3-fluoro-4',5'-dimethoxybiphenyl-4-yl)-5-(4-decyloxyphenoxy)-1,3,4 -furadiazole-2(3H)-one 96-97 3-(3- gas-4'-avidylbiphenyl-4-yl)-5-(4-decyloxyphenyl)-1, 3,4-bite two ° sit-2(311)-嗣132-133 3-(4-fluorophenyl)-5-(4-decyloxyphenoxy)-1,3,4-furadiazole -2(3H)-keto 108-109 3-(4-Gas-2-fluorophenyl)-5-(4-decyloxyphenoxy)-1,3,4-furadiazole-2 (3H )-嗣89-90 5-(4-decyloxyphenoxy)-3-(4-methoxyphenyl)-1,3,4-furadiazole-2(3H)-one 100-101.5 5-(4-Vephenoxy)-3-(4-methoxyphenyl)-1,3,4-furadiazole-2(3H)-one 98-99 3-(4·-( Methylamino)-3-cyclobiphenyl-4-yl)-5-(4-methylrylphenoxy)-1,3,4-furadiazole-2(3H)-one 160-161 5-(4-Vephenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 146-147 3-(4-bromophenyl)- 5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2(3H)-one 114-115 5-(4-bromo-2-indolylphenoxy)- 3-phenyl-1,3,4-furadiazole-2(3H)-one 77-78 5-(3,5-dimethoxyphenoxy)-3-(2-fluorophenyl)- 1,3,4-furadiazole-2(3H)-阙97-98 5-(4-cyanophenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole -2(3H)-ketone 125-126 3-(2-fluorophenyl)-5-(naphthalen-2-yloxy)-1,3,4-furadiazole-2(311)-one 101-102 3-phenyl-5-(pyridin-3-yloxy)-1,3,4-furadiazole-2(311)-ketone 88-89 3-(4-(1Η-tetrazol-5-yl) Phenyl)-5-phenyloxy-1,3,4-furadiazole-2(3H)-one 201-202 3-(5-bromo-2-fluorophenyl)-5-(4-gasbenzene Oxy)-1,3,4-furadiazole-2(3H)-one 107-108 5-(4-fluorophenoxy)-3-(4-hydroxyphenyl)-1,3,4- Furadiazole-2(3H)-one 155-156 5-(4-(1H-tetrazol-5-yl)phenoxy)-3-(2-fluorophenyl)-1,3,4-furan Diazole-2(3H)-one 153-154 5-(3,4-dimethoxyphenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2 ( 3H)-ketone 82. 5-83 5-(2,4-Difluorophenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 174-175 3-(2 -fluoro-4-(methylsulfonyl)phenyl)-5-(4-decyloxyphenoxy)-1,3,4-furadiazole-2(3H)-one 95-96 200932732 5 -(4-fluorophenoxy)-3-(4-methoxyphenyl)-1,3,4-furadiazole-2(3H)-one 89-90 5-(biphenyl-4- Oxyxy)-3-(2-fluorophenyl)-l,3,4-furadiazole-2(3H)-one 81-81 3-(2-fluorophenyl)-5-(3,4, 5-trimethoxyphenoxy)-1,3,4-furadiazole-2(3H)-ketone 139-140 3-(4-oxo tombylphenyl)-5-(3-(trifluoromethyl) Phenyloxy)-1,3,4-oxadiazole-2(3H)-one 70-71 3-(4-methoxyphenyl)-5-(p-tolyloxy)-1, 3,4-furadiazole-2(3H)-one 83-84 3-(4-hydroxyphenyl)-5-(p-tolyloxy)-1,3,4-furadiazole-2 (3H )-ketone 159-160 3-(3-Gas-2-fluorophenyl)-5-(4-methoxyphenoxy)-1,3,4-furadiazole-2(3H)-_ 102 -103 3-(4-Hydroxyphenyl)-5-(3-(trifluoromethyl)phenoxy)-1,3,4-furadiazole-2(3H)-one 167-168 5-(节oxy)-3-(3-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 101-102 3-(3-fluorophenyl)-5-(4-A Oxyphenoxy)-1,3,4-furadiazole-2(3H)-one 84-85 5-(3,5-dihydroxyphenoxy)-3-( 2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 155-156 3-(4-methoxyphenyl)-5-(pyridin-3-yloxy)-1 ,3,4-furadiazole-2(3H)-one 79-80 5-(2-Ga-4-hydroxyphenoxy)-3-(2-fluorophenyl)-1,3,4-furan Diazole-2(3H)-one 122-123 3-(5-Gas-2-fluorophenyl)-5-(4-methoxyphenoxy)-1,3,4-furodi--2 (3H)-_ 85-86 3-(4-Hydroxyphenyl)-5-(4-nitrophenoxy)-1,3,4-furadiazole-2(3H)-one 174-175 5 -(2,4-diphenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 177-178 3-(2-fluorophenyl -5-(3-hydroxyphenoxy)-1,3,4-furadiazole-2(3H)-one 140-141 3-(2-fluorophenyl)-5-(acridin-3- Base oxygen)-1,3,4-furadiazole-2(3H)-one 63-64 3-(2,4-difluorophenyl)-5-(pyridin-3-yloxy)-1,3 , 4-furadiazole-2(3H)-one 89-90 3-(2-fluoro-4-(methylsulfonyl)phenyl)-5-(acridin-3-yloxy)-1, 3,4-furadiazole-2(3H)-one 100-100 5-(2-bromopyridin-3-yloxy)-3-(4-methoxyphenyl)-1,3,4-furan Diazole-2(3H)-one 116-117 5-(2,4-di-tert-butylphenoxy)-3-(2-fluorophenyl)-1,3,4-bite two-degree sitting -2(3H)-keto oil 5-(cyclohexyloxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 58-59 5-(2 ,6-dimethylphenoxy) -3-(2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 88-89 3-(3-Gas-2-fluorophenyl)-5-(cyclohexyloxy) -1,3,4-furadiazole-2(3H)-one 84-85 5-(cyclohexyloxy)-3-(4-methoxyphenyl)-1,3,4-furan Diazole-2(3H)-one 71-72 3-(2,4-difluorophenyl)-5-(2,6-dimethoxyphenoxy)-1,3,4-oxadiazole -2(3H)-ketone 94-95 hexyl)-3-(3-gas_4',5'-di- acetophenylbiphenyl-4-yl)-1,3,4-bito sigma -2(3H)-嗣101-102 3-(3-hydroxyphenyl)-5-phenoxy-1,3,4-furadiazole-2(311)-one 116-117 5-(ring Hexyloxy)-3-(3-fluoro-3'-(trifluoromethoxy)biphenyl-4-yl)-1,3,4-furadiazole-2(3H)-one 91-92 5-(4-Vephenoxy)-3-(3-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 166-167 5-(4-fluorophenoxy) -3-(3-hydroxyphenyl)-1,3,4-furadiazole-2 (3-acetone 163-164 3-(4-disorder-2-phenylphenyl)-5-phenylethoxy -1,3,4-bite 2° sitting-2(311)-明52-53 103 200932732 3-(4-hydroxyphenyl)-5-phenylethoxy-1,3,4-furadiazole- 2(3H)-ketone 148-149 3-(2-fluorophenyl)-5-isobutoxy-1,3,4-furadiazole-2(3H)-one oil 3-(4-hydroxybenzene 5-(3-phenylpropoxy)-1,3,4-furadiazole-2(3H)-one 129-130 3-(4-hydroxyl 5-(4-phenylbutoxy)-1,3,4-furadiazole-2(3H)-one 120-121 3-(4-hydroxyphenyl)-5-(5-benzene Pentyloxy)-1,3,4-furadiazole-2(3H)-one 128-128 3-(4-hydroxyphenyl)-5-(6-phenylhexyloxy)-1,3, 4-furadiazole-2(3H)-one 107-108 3-(4-Amino-nonylphenyl)-5-(4-fluorophenoxy)-1,3,4-furadiazole- 2(3H)-ketone 217-218 3-(4-Aminosulfonicylphenyl)-5-(4-decyloxyphenoxy)-1,3,4-furadiazole-2 (3H) -ketone 191-192 3-(4-hydroxyphenyl)-5-(2-phenoxyethoxy)-l,3/l·furadiazole-2(3H)-one 164-165 5-( 2-oxophenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 139-140 3-(4-Aminophenylphenyl) -5-(4-Vephenoxy)-1,3,4-furadiazole-2(3H)-one 227-228 3-(4-Aminosulfonylphenyl)-5-phenoxy Base-1,3,4-furadiazole-2(3H)-one 204-205 3-phenyl-5-(5-phenylpentyloxy)-1,3,4-furadiazole-2 ( 3H)-keto 50-51 3-(2-fluorophenyl)-5-(4-phenylbutoxy)-1,3,4-furadiazole-2(3H)-one oil 3-(4 -aminosulfonylphenyl)-5-(5-phenylpentyloxy)-1,3,4-furadiazole-2(3H)-one 143-144 3-(2-fluorophenyl) -5-(5-phenylpentyloxy)-1,3,4-furadiazole-2(3H)-one oil 3-(2,4 -difluorophenyl)-5-(5-phenylpentyloxy)-1,3,4-furadiazole-2(3H)-one 40-41 5-(4-(3,4-dimethyl Oxyphenyl)butoxy)-3-phenyl-1,3,4-furadiazole-2(3H)-one 56-57 3-(2-a-5-fluorophenyl)-5- (5-phenylpentyloxy)-1,3,4-furadiazole-2(3H)-one oil 5-(4-(3,4-dimethoxyphenyl)butoxy)-3 -(2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one oil 5-(2-phenylphenoxy)-3-(2-fluorophenyl)-1, 3,4-furadiazole-2(3H)-one 79-80 3-(2,4-difluorophenyl)-5-(4-(3,4-dimethoxyphenyl)butoxy -1,3,4-furadiazole-2(3H)-keto oil 3-(4-Gas-2-fluorophenyl)-5-(4-(3,4-dimethoxyphenyl) Butoxy)-1,3,4-furo-sigma-2(3H)-indole oil 3-(3-gas-2-fluorophenyl)-5-(4-(3,4-dimethoxy) Phenyl)butoxy)-1,3,4-furodioxa-2(3H)-indole oil 3-(4-aminocarbonylphenyl)-5-phenoxy-1,3,4- Furadiazole-2(3H)-one 226-227 3-(4-Aminosulfonylphenyl)-5-(4-(3,4-dimethoxyphenyl)butoxy)-1 ,3,4-furadiazole-2(3H)-one 148-149 3-(2-fluorophenyl)-5-(4-(4-fluorophenyl)butoxy)-1,3,4 -furadiazole-2(3H)-one oil 3-(4-aminocarbonylphenyl)-5-(4-phenoxy)-1,3,4-furadiazole-2(3H)- 240-241 3-(4-Aminocarbonylphenyl)-5-(4-methoxyphenoxy)-1,3,4-furadiazole-2(3H)-one 190-191 3-( 4-aminocarbonylphenyl)-5-(4-(4-fluorophenyl)butoxy)-1,3,4-furadiazole-2(3H)-one 142-142 3-(4- Aminocarbonylphenyl)-5-(5-(4-fluorophenyl)pentyloxy)-1,3,4-furadiazole-2(3H)-one 155-156 3-(4-Amino Carbonyl phenyl)-5-(4-p-tolylbutoxy)-1,3,4-furadiazole-2(3H)-one 154-155 200932732

3-(4-胺基羰基苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑-2(3H)-酮 150-151 5-(聯苯基-4-基氧)-3-(4-羥基苯基)-1，3,4-呋二唑-2(3H)-酮 186-187 5-(4-胺基羰基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 132-133 5-(2-氟苯氧基)-3-(4-甲氧基苯基)-1,3,4-呋二唑-2(3H)-酮 64-65 5-(3,4-二氟苯氧基)-3-(4-甲氧基苯基)-1,3,4-呋二唑-2(3H)-酮 86-87 5-(2-氟苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 185-186 5-(3,4-二氟苯氡基)-3-(4-羥基苯基)-1，3,4-呋二唑-2(3H)-酮 152-153 3-(3-胺基苯基)-5-苯氧基-1，3,4-呋二唑-2(3H)-酮 89-90 3-(3-胺基苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑-2(3H)-酮 122-123 5-(2-(聯苯基-4-基）乙乳基)-3-(4- _坐基苯基)-1，3,4-咬二17坐 -2(3H)-酮 167-168 5-(2,4-二氟苯氧基)-3-(3,4-二曱氧基苯基)-1,3,4-呋二唑 -2(3H)-酮 97-98 5-(4-氣苯氧基)-3-(3,4-二羥基苯基)-1，3,4-呋二唑-2(3H)-酮 167-168 5-(2/l· 二氟苯氧基)-3-(3,4-二羥基苯基)-1,3,4-呋二唑-2(3H)-酮 167-168 5-(2,4-二氟苯氧基)-3-(3-甲氧基苯基)-1，3,4-呋二唑-2(3H)-_ 78-79 5-(3,4-二甲氧基苯氧基)-3-(4-氟苯基)-1,3,4-呋二唑-2(3H)-酮 98-99 5-(3,4-二羥基苯氧基)-3-(4-氟苯基)-1,3,4-呋二唑-2(3H)-酮 138-139 3-(3-氟苯基)-5-(4-羥基苯氧基)-1,3,4-呋二唑-2(3H)-酮 139-140 5-(2,4-二氟苯氧基)-3-(3-羥基苯基)-1，3,4-呋二唑-2(3H)-酮 163-164 5-(2-氣苯氧基)-3-(3-曱氧基苯基)-1,3,4-呋二唑-2(3H)-酮 105-106 3-(4-氣-2-氟苯基)-5-(4-羥基苯氧基)-1，3,4-呋二唑-2(3H)-酮油 3-(4-氟苯基)-5-(4-羥基苯氧基)-1，3,4-呋二唑-2(3H)-酮 130 5-(3,5-二氟苯乙氧基)-3-(4-羥基苯基)-1，3,4-呋二唑-2(3H)-酮 126-127 5-(2-氣苯氧基)-3-(3-羥基苯基)-1，3,4-吱二唑-2(3H)-酮 125-126 5-(4-氣苯氧基)-3-(2'-羥基聯苯基-4-基)-1,3,4-呋二唑-2(3H)-酮 160-161 3-(3-氣-2-氣苯基)-5-(4-經基笨氧基油 5-(4-氣苯氧基)-3-(2’-甲氧基聯苯基-4-基)-1,3,4-呋二唑 -2(3H)-酮 86-87 5-(3,4-二羥基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 140-141 5-(4-氣笨氧基)-3-(3-氟-4-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 152-153 5-(2,4-二氟苯氧基)-3-(2’-甲氧基聯苯基-4-基)-1,3,4-呋二唑 -2(3H)-酮 106-107 5-(4-氣苯氧基)-3-(2-氟-4-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 180-182 5-(4-氣苯氧基)-3-(2'-羥基聯苯基-3-基)-1,3,4-呋二嗤-2(3均-酮 112-113 5-(2,4-二氟苯氧基)-3-(4-羥基-3-甲基苯基)-1,3,4-呋二唑 -2(3H)-酮 147-148 124-125 5-(4-氣苯氧基)-3-(4-羥基-3-曱基苯基)-l，3,4-呋二唑-2(3H)-酮 200932732 5-(2,4-二氟苯氧基)-3-(2'-羥基聯苯基-4-基)-1,3,4-呋二唑 -2(3H)-酮 161-162 5-(4-氣苯氧基)-3-(2'-曱氧基聯苯基-3-基)-1,3,4-呋二唑 -2(3H)-酮 108-109 5-(2,4-二氟苯氧基)-3-(4-羥基-3,5-二甲基苯基)-1,3,4-呋二唑 -2(3H)-酮 112-113 5-(4-氣苯氧基)-3-(4-羥基-3,5-二甲基苯基)-1,3,4-呋二唑 -2(3H)-酮 145-146 5-(2,4-二氟苯氧基)-3-(4-(4-甲氧基苄氧基)苯基)-1,3,4-呋二唑-2(3H)-酮 122 5-(2,4-二氟苯氧基)-3-(4-(3-曱氧基苄氧基)苯基)-1,3,4-呋二嗤-2(311)-嗣 101 5-(4-氣笨氧基)-3-(3,5-二羥基苯基)-1,3,4-呋二唑-2(3H)-酮 213 5-(2,4-二氟苯氧基)-3-(4-(2-曱氧基苄氧基)苯基)-1,3,4-呋二 °^.-2(3Η)-ί^ 75-76 3-(4-苯曱醯基氧苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑-2(3Η)-酮 159 3-(4-乙醯氧基苯基)-5-(2,4-二氟苯氧基）-1,3,4-呋二唑 -2(3Η)-酮 160 3-(4-苯甲醯基氧苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑 -2(3Η)-酮 143 3-(4-異丁醯基氧苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑 -2(3Η)-酮 89-90 5-(2,4-二氟苯氧基)-3-(3-甲氧基-4-硝基苯基)-1,3,4-呋二唑 -2(3Η)-酮 133 5-(2,4-二氟苯氧基)-3-(3-羥基-4-硝基苯基)-1，3,4-呋二唑 -2(3Η)-酮 129 5-(4-氣苯氧基)-3-(3-羥基-4-硝基苯基)-1，3,4-呋二唑-2(3Η)-酮 160-161 5-(2,4-二氟苯氧基)-3-(7-羥基萘-2-基)-1,3,4-呋二唑-2(3Η)-酮 181 3-(4-胺基-3-羥基苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑 -2(3Η)-酮 226-228 3-(4-胺基-3-甲氧基苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑 -2(3Η)-酮鹽酸鹽 200-201 3-(4-胺基-3-(2-曱氧基乙氧基）苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑-2(3Η)-酮 79 3-(4-胺基苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑-2(3Η)-酮 152-153 3-(4-(1Η-吼咯-1-基)苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑 -2(3Η)-酮 181-182 3-(4-胺基苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑-2(3Η)-酮 112 3-(4-( 1Η- °比咯-1 -基）苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑 -2(3Η)_ 酮 175 3-(3-胺基-4-甲氧基苯基)-5-(對-甲苯基氧)-1,3,4-呋二唑 -2(3Η)-酮 113 3-(3-胺基-4-曱氧基苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑 -2(3Η)-酮 101 3-(3-胺基-4-甲氧基笨基)-5-(環己氧基)-1，3,4-呋二唑-2(3Η)-酮鹽酸鹽 185 5-(2,4-二氟苯氧基）-3-(4-甲氧基-3-(1Η-吼咯-1-基）苯基)-1,3,4-呋二唑-2(311)-酮 136 3-(5-胺基-2-氟-4-甲氧基苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑-2(3Η)-酮鹽酸鹽 191-192 分解 5-(2,4-二氟苯氧基）-3-(2-氟-4-羥基苯基）-1,3,4-呋二唑 -2(3Η)-酮 135 3-(4-胺基-3-甲氧基苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑 -2(3Η)-酮 104-105 106 200932732 所製得的油類之NMR數據係示於下列第2表中。在以溶劑作為内部標準之布魯克(Bruker)公司的愛文斯(Avance) DPX400型光譜儀上，記錄NMR光譜。數據係依下列順序報導：化學位移近似值(PPm)、質子數目、多重性(br:寬廣； 5 d :雙峰；m :多重峰；s :單峰；t :三峰)及偶合常數(Hz)。第2表3-(4-Aminocarbonylphenyl)-5-(5-phenylpentyloxy)-1,3,4-furadiazole-2(3H)-one 150-151 5-(biphenyl- 4-yloxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 186-187 5-(4-Aminocarbonylphenoxy)-3- (2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 132-133 5-(2-fluorophenoxy)-3-(4-methoxyphenyl)- 1,3,4-furadiazole-2(3H)-one 64-65 5-(3,4-difluorophenoxy)-3-(4-methoxyphenyl)-1,3,4 -furadiazole-2(3H)-one 86-87 5-(2-fluorophenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)- Ketone 185-186 5-(3,4-difluorophenylhydrazino)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 152-153 3-( 3-aminophenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 89-90 3-(3-aminophenyl)-5-(2,4 -difluorophenoxy)-1,3,4-furadiazole-2(3H)-one 122-123 5-(2-(biphenyl-4-yl)ethylidyl)-3-(4 - _sitylphenyl)-1,3,4-bita 2-17--2(3H)-ketone 167-168 5-(2,4-difluorophenoxy)-3-(3,4-di曱oxyphenyl)-1,3,4-furadiazole-2(3H)-one 97-98 5-(4-phenoxy)-3-(3,4-dihydroxyphenyl)- 1,3,4-furadiazole-2(3H)-one 167-168 5-(2/l·difluorophenoxy)-3-(3,4-dihydroxyphenyl) -1,3,4-furadiazole-2(3H)-one 167-168 5-(2,4-difluorophenoxy)-3-(3-methoxyphenyl)-1,3, 4-furadiazole-2(3H)-_ 78-79 5-(3,4-dimethoxyphenoxy)-3-(4-fluorophenyl)-1,3,4-furadiazole -2(3H)-keto 98-99 5-(3,4-dihydroxyphenoxy)-3-(4-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 138-139 3-(3-Fluorophenyl)-5-(4-hydroxyphenoxy)-1,3,4-furadiazole-2(3H)-one 139-140 5-(2,4- Difluorophenoxy)-3-(3-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 163-164 5-(2-phenoxy)-3-( 3-methoxyphenyl)-1,3,4-furadiazole-2(3H)-one 105-106 3-(4-Gas-2-fluorophenyl)-5-(4-hydroxyphenoxy -1,3,4-furadiazole-2(3H)-keto oil 3-(4-fluorophenyl)-5-(4-hydroxyphenoxy)-1,3,4-furadiazole -2(3H)-one 130 5-(3,5-difluorophenylethoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 126 -127 5-(2-Vinyloxy)-3-(3-hydroxyphenyl)-1,3,4-oxadiazole-2(3H)-one 125-126 5-(4-Phenyloxyl 3-(2'-hydroxybiphenyl-4-yl)-1,3,4-furadiazole-2(3H)-one 160-161 3-(3-Ga-2-phenylphenyl) -5-(4-pyridyloxy oil 5-(4-phenoxy)-3-(2'-methoxybiphenyl-4-yl)-1,3,4-fur Diazole-2(3H)-one 86-87 5-(3,4-dihydroxyphenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2 (3H) -ketone 140-141 5-(4-oxaphenyloxy)-3-(3-fluoro-4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 152-153 5 -(2,4-difluorophenoxy)-3-(2'-methoxybiphenyl-4-yl)-1,3,4-furadiazole-2(3H)-one 106-107 5-(4-Vephenoxy)-3-(2-fluoro-4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 180-182 5-(4-gas Phenoxy)-3-(2'-hydroxybiphenyl-3-yl)-1,3,4-furodiindole-2 (3-homo-ketone 112-113 5-(2,4-difluorobenzene) Oxy)-3-(4-hydroxy-3-methylphenyl)-1,3,4-furadiazole-2(3H)-one 147-148 124-125 5-(4-phenoxy) )-3-(4-hydroxy-3-indolylphenyl)-l,3,4-furadiazole-2(3H)-one 200932732 5-(2,4-difluorophenoxy)-3- (2'-Hydroxybiphenyl-4-yl)-1,3,4-furadiazole-2(3H)-one 161-162 5-(4-phenoxy)-3-(2'- Oxyloxybiphenyl-3-yl)-1,3,4-furadiazole-2(3H)-one 108-109 5-(2,4-difluorophenoxy)-3-(4- Hydroxy-3,5-dimethylphenyl)-1,3,4-furadiazole-2(3H)-one 112-113 5-(4-phenoxy)-3-(4-hydroxy- 3,5-Dimethylphenyl)-1,3,4-furadiazole-2(3H)-one 145-146 5-(2,4-difluorophenoxy) 3-(4-(4-methoxybenzyloxy)phenyl)-1,3,4-furadiazole-2(3H)-one 122 5-(2,4-difluorophenoxy) -3-(4-(3-decyloxybenzyloxy)phenyl)-1,3,4-furodiindole-2(311)-嗣101 5-(4-indolyloxy)-3- (3,5-dihydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 213 5-(2,4-difluorophenoxy)-3-(4-(2-曱苄 benzyloxy)phenyl)-1,3,4-furodi^.-2(3Η)-ί^ 75-76 3-(4-benzofluorenyloxyphenyl)-5-( 4-Vephenoxy)-1,3,4-furadiazole-2(3Η)-one 159 3-(4-Ethyloxyphenyl)-5-(2,4-difluorophenoxy )-1,3,4-furadiazole-2(3Η)-one 160 3-(4-Benzylnonyloxyphenyl)-5-(2,4-difluorophenoxy)-1,3 , 4-furadiazole-2(3Η)-one 143 3-(4-isobutylphosphonyloxyphenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole- 2(3Η)-keto 89-90 5-(2,4-difluorophenoxy)-3-(3-methoxy-4-nitrophenyl)-1,3,4-furadiazole- 2(3Η)-ketone 133 5-(2,4-difluorophenoxy)-3-(3-hydroxy-4-nitrophenyl)-1,3,4-furadiazole-2(3Η) -keto 129 5-(4-phenoxy)-3-(3-hydroxy-4-nitrophenyl)-1,3,4-furadiazole-2(3Η)-one 160-161 5- (2,4-difluorophenoxy)-3-(7-hydroxynaphthalen-2-yl)-1,3,4-furadiazole-2(3Η)-one 1 81 3-(4-Amino-3-hydroxyphenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2(3Η)-one 226-228 3 -(4-Amino-3-methoxyphenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2(3Η)-one hydrochloride 200 -201 3-(4-Amino-3-(2-decyloxyethoxy)phenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole- 2(3Η)-keto 79 3-(4-Aminophenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2(3Η)-one 152- 153 3-(4-(1Η-吼rol-1-yl)phenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2(3Η)-one 181-182 3-(4-Aminophenyl)-5-(4-phenoxy)-1,3,4-furadiazole-2(3Η)-one 112 3-(4-( 1Η- °Byr-1 -yl)phenyl)-5-(4-phenoxy)-1,3,4-furadiazole-2(3Η)_one 175 3-(3-Amino-4- Methoxyphenyl)-5-(p-tolyloxy)-1,3,4-furadiazole-2(3Η)-one 113 3-(3-Amino-4-methoxyphenyl) -5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2(3Η)-one 101 3-(3-Amino-4-methoxyphenyl)-5 -(cyclohexyloxy)-1,3,4-furadiazole-2(3Η)-one hydrochloride 185 5-(2,4-difluorophenoxy)-3-(4-methoxy -3-(1Η-吼rol-1-yl)phenyl)-1,3,4-furadiazole-2(311)-one 1 36 3-(5-Amino-2-fluoro-4-methoxyphenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2 (3Η) -ketohydrochloride 191-192 Decomposes 5-(2,4-difluorophenoxy)-3-(2-fluoro-4-hydroxyphenyl)-1,3,4-furadiazole-2 (3Η )-keto135 3-(4-Amino-3-methoxyphenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2(3Η)- The NMR data of the oils obtained by the ketones 104-105 106 200932732 are shown in Table 2 below. The NMR spectrum was recorded on an Avance DPX400 spectrometer from Bruker, Inc. using the solvent as an internal standard. The data are reported in the following order: chemical shift approximation (PPm), number of protons, multiplicity (br: broad; 5 d: doublet; m: multiplet; s: singlet; t: triple) and coupling constant (Hz) . Table 2

化合物 NMR數據 5-(节氧基)-3-(2,5-二T基笨基)-1，3,4-吱二吐-2(如)痛 (*ΗΝΜΚ, CDC13, 400ΜΗζ) δ ： 7.49-7.40 (5H, m), 7.19(2H, m), 7.13(1H, dd, J=1.5 M 7.8), 5.34(2H, s), 2.35(3H, s), 2.28(3H, s) (13CNMR, CDC13, 100M) δ ： 154.9, 149.5, 136.5, 133.3, 133.1, 131.7, 131.0, 129.9, 129.1, 128.6, 128.5, 126.7,72.6, 20.9, 17.8 3-(2-氟笨基)-5-(4-f氧基笨氧基)-1,3,4-吱二唑-2(3扣-_ (^NMR, CDC13, 400M) δ ： 7.48 (1H, dt, J=1.7, 7.6), 7.38(1H, m), 7.30(2H, m, J=9.3), 7.21(2H, m), 6.94(2H, m, J=9.3), 3.84(3H, s) (13CNMR, CDCI3, 100M) δ ： 157.6, 156.2(d, J=254), 154.9, 148.8, 144.7, 130.2(d, J=8), 127.0, 124.4(d, J=4), 122.6(d, J=12), 120.6, 116.8(d, J=19), 114.7, 55.7 3-(2,4-二氟苯_基)-5-(3-(二氟甲基）苯氧基)-1，3,4-吱二令2(3H)-酮 (^NMR, CDCI3, 400M) 6 ： 7.68(1H, m), 7.62(3H, m), 7.50(1H, m), 6.99(2H, m) (13CNMR, CDCI3, 100M) δ ： 162.5(dd, J=ll 與 252)，156.8(dd, J=13 與 257)， 153.8, 151.1，148.6, 132.4(q，J=34)， 130.6, 128.2(dd，J=1 與 10)，123.5(q， J=3.5), 122.9(q, J=271), 122.8, 118.8(dd, J=4 與 12)，116.8(q, J=4)，111.9(dd，J=4 與 23), 105.4(dd，J=23 與 26) 3_(2_氣笨基)-5-苯氧基-1，3,4-呋二嗤，2(3H)-_ (•HNMR, CDCI3, 400M) δ ： 7.50-7.30 (8H, m), 7.27(m, 1H) (13CNMR, CDCI3, 100M) δ ： 154.1, 151.3, 149.0, 132.0(2sig.), 130.7, 130.5, 129.8, 128.9, 127.5, 126.6, 119.3 107 200932732 5-(2,4-二-特-丁基苯氧基)-3- (2-氟苯基)-1,3,4-呋二唑-2(311)-酮 (*HNMR, CDC13, 400M) δ ： 7.48( 1H, m, J=2 與 8)，7.43(1H, d，J=2.5)，7·37(1Η， m)，7.26( 1H，dd，J=2.5 與 8.6)，7.24-7.16 (3H, m), 1.42(9H, s), 1.32(9H, s) (13CNMR, CDCI3, 100M) δ ： 156.5(d, J=255), 154.8, 149.3, 149.2, 148.2, 139.6, 130.4(d, J=7.5), 127.1, 124.7, 124.5(d, J=4), 124.3, 120.3, 117.0(d, J=19.5), 34.9,34.7, 31.4, 31.3 3-(2-氟苯基)-5-異丁氧基-1，3,4-呋二 ϋ坐 _2(3H)-嗣 (*HNMR, CDCI3, 400M) δ ： 7.54(1H, m, J=2 M 8.3), 7.41 (1H, m), 7.25(2H, m), 4.15(2H, d, J=6.6), 2.18(1H, m), 1.06 (6H, d, J=6.6) (13CNMR, CDCI3, 100M) 6 ： 156.4(d, J=254), 155.9, 149.3, 130.2(d, J=7.5), 126.9, 124.6(d, J=4), 122.9(d, J=11.5), 117.0(d, J=19.5), 77.2, 27.7, 18.6 3-(2-氟笨基)-5-(4-苯基丁氧基)-1,3,4-呋二唑-2(311)-酮 (^NMR, CDCI3, 400M) δ ： 7.53( 1H, m), 7.41(1H, m), 7.33(2H, t, J=7.5), 7.29-7.19(5H, m), 4.39(2H, t, J=6.3), 2.72 (2H, t, J=7.3), 1.90(2H, m), 1.80(2H, m) (13CNMR, CDCI3, 100M) δ ： 156.4(d, J=255), 155.8, 149.3, 141.5, 130.2(d, J=8), 128.4(2sig.), 126.9, 126.0, 124.6(d, J=4), 123.0(d, J=11.5), 117.0(d, J=20), 71.4,35.2, 27.8, 27.1 3-(2-氣苯基)-5-(5-苯基戍基氧)-1,3,4-呋二唑-2(311)-酮 (^NMR, CDCI3, 400M) δ ： 7.51(1H, m, J=2 與 7.8)，7.39(1H，m), 7.30(2H, m， J=7.5), 7.27-7.15(5H, m), 4.35(2H, t, J=6.6), 2.66(2H, t, J=7.3), 1.86(2H, m), 1.70(2H, m), 1.50(2H, m) (13CNMR, CDCI3, 100M) δ ： 156.4(d, J=255), 155.8, 149.3, 142.1, 130.2(d, J=8), 128.4, 128.3, 126.9, 125.8, 124.6 (d, J=4), 123.0(d, J=11.5), 117.0(d, J=19.3), 71.5, 35.7, 30.9, 28.2, 25.1 3-(2-氯-5-氣苯基)-5-(5-苯基戍基氧)-1,3,4-呋二唑-2(3H)-酮 (•HNMR, CDCI3, 400M) δ ： 7.53(1H, dd, J=2.7 M 6.5), 7.33(1H, m), 7.30(2H, t, J=7.3), 7.23-7.16(4H, m), 4.35(2H, t, J=6.6), 2.65(2H, t, J=7.8), 1.86(2H, m), 1.70(2H, m), 1.50(2H, m)Compound NMR data 5-(hydroxy)-3-(2,5-di-T-phenyl)-1,3,4-anthracene-2 (eg) Pain (*ΗΝΜΚ, CDC13, 400ΜΗζ) δ : 7.49-7.40 (5H, m), 7.19(2H, m), 7.13(1H, dd, J=1.5 M 7.8), 5.34(2H, s), 2.35(3H, s), 2.28(3H, s) ( 13CNMR, CDC13, 100M) δ: 154.9, 149.5, 136.5, 133.3, 133.1, 131.7, 131.0, 129.9, 129.1, 128.6, 128.5, 126.7, 72.6, 20.9, 17.8 3-(2-fluorophenyl)-5-( 4-f-oxyphenyloxy)-1,3,4-oxadiazole-2 (3 -3 (^NMR, CDC13, 400M) δ : 7.48 (1H, dt, J=1.7, 7.6), 7.38 (1H, m), 7.30(2H, m, J=9.3), 7.21(2H, m), 6.94(2H, m, J=9.3), 3.84(3H, s) (13CNMR, CDCI3, 100M) δ : 157.6, 156.2(d, J=254), 154.9, 148.8, 144.7, 130.2(d, J=8), 127.0, 124.4(d, J=4), 122.6(d, J=12), 120.6, 116.8( d, J=19), 114.7, 55.7 3-(2,4-difluorophenyl-yl)-5-(3-(difluoromethyl)phenoxy)-1,3,4-anthracene 2 (3H)-ketone (^NMR, CDCI3, 400M) 6 : 7.68 (1H, m), 7.62 (3H, m), 7.50 (1H, m), 6.99 (2H, m) (13CNMR, CDCI3, 100M) δ : 162.5 (dd, J=ll and 252), 156.8 (dd, J=13 and 257), 153.8, 151.1, 148.6, 132.4 (q, J=34), 130.6, 1 28.2 (dd, J=1 and 10), 123.5 (q, J=3.5), 122.9 (q, J=271), 122.8, 118.8 (dd, J=4 and 12), 116.8 (q, J=4) , 111.9 (dd, J=4 and 23), 105.4 (dd, J=23 and 26) 3_(2_qiqiji)-5-phenoxy-1,3,4-furodiindole, 2 (3H )-_ (•HNMR, CDCI3, 400M) δ: 7.50-7.30 (8H, m), 7.27(m, 1H) (13CNMR, CDCI3, 100M) δ : 154.1, 151.3, 149.0, 132.0 (2sig.), 130.7 , 130.5, 129.8, 128.9, 127.5, 126.6, 119.3 107 200932732 5-(2,4-Di-tert-Butylphenoxy)-3-(2-fluorophenyl)-1,3,4-furo Azole-2(311)-one (*HNMR, CDC13, 400M) δ : 7.48 ( 1H, m, J=2 and 8), 7.43 (1H, d, J=2.5), 7·37 (1Η, m) , 7.26 ( 1H, dd, J = 2.5 and 8.6), 7.24 - 7.16 (3H, m), 1.42 (9H, s), 1.32 (9H, s) (13CNMR, CDCI3, 100M) δ : 156.5(d, J =255), 154.8, 149.3, 149.2, 148.2, 139.6, 130.4 (d, J=7.5), 127.1, 124.7, 124.5 (d, J=4), 124.3, 120.3, 117.0 (d, J=19.5), 34.9 , 34.7, 31.4, 31.3 3-(2-Fluorophenyl)-5-isobutoxy-1,3,4-furodiindole _2(3H)-嗣(*HNMR, CDCI3, 400M) δ : 7.54 (1H, m, J=2 M 8.3), 7.41 (1H, m), 7.25(2H, m), 4.15(2H, d, J=6.6), 2.18(1H , m), 1.06 (6H, d, J=6.6) (13CNMR, CDCI3, 100M) 6 : 156.4 (d, J=254), 155.9, 149.3, 130.2 (d, J=7.5), 126.9, 124.6 (d , J=4), 122.9(d, J=11.5), 117.0(d, J=19.5), 77.2, 27.7, 18.6 3-(2-Fluorophenyl)-5-(4-phenylbutoxy) -1,3,4-furadiazole-2(311)-one (^NMR, CDCI3, 400M) δ : 7.53 ( 1H, m), 7.41 (1H, m), 7.33 (2H, t, J = 7.5 ), 7.29-7.19(5H, m), 4.39(2H, t, J=6.3), 2.72 (2H, t, J=7.3), 1.90(2H, m), 1.80(2H, m) (13CNMR, CDCI3) , 100M) δ : 156.4(d, J=255), 155.8, 149.3, 141.5, 130.2(d, J=8), 128.4(2sig.), 126.9, 126.0, 124.6(d, J=4), 123.0( d, J=11.5), 117.0 (d, J=20), 71.4, 35.2, 27.8, 27.1 3-(2-phenylphenyl)-5-(5-phenylindenyloxy)-1,3,4 -furadiazole-2(311)-one (^NMR, CDCI3, 400M) δ: 7.51 (1H, m, J=2 and 7.8), 7.39 (1H, m), 7.30 (2H, m, J=7.5 ), 7.27-7.15(5H, m), 4.35(2H, t, J=6.6), 2.66(2H, t, J=7.3), 1.86(2H, m), 1.70(2H, m), 1.50(2H , m) (13CNMR, CDCI3, 100M) δ : 156.4 (d, J=255), 155.8, 149.3, 142.1, 130.2 (d, J=8), 128.4, 128.3, 126.9, 125.8, 124.6 (d, J= 4), 123.0 (d, J = 11.5), 117.0 (d, J = 19.3), 71 .5, 35.7, 30.9, 28.2, 25.1 3-(2-Chloro-5-phenylphenyl)-5-(5-phenylindolyloxy)-1,3,4-furadiazole-2 (3H) -ketone (•HNMR, CDCI3, 400M) δ: 7.53 (1H, dd, J=2.7 M 6.5), 7.33(1H, m), 7.30(2H, t, J=7.3), 7.23-7.16(4H, m ), 4.35(2H, t, J=6.6), 2.65(2H, t, J=7.8), 1.86(2H, m), 1.70(2H, m), 1.50(2H, m)

108 200932732108 200932732

(13CNMR, CDC13, 100M) δ ： 156.0, 154.6(d, J=255), 148.8, 142.0, 129.8(d, J=7.5), 129.5(d, J=4), 128.4, 128.3, 126.3, 125.8, 124.0, 118.2(d, J=21), 71.7, 35.7, 30.9, 28.2, 25.1 5-(4-(3,4-二甲氧基苯基)丁氧基)-3-(2-氟苯基)-1,3,4-呋二唑 -2(3H)-酮 ('HNMR, CDCI3, 400M) δ ： 7.51(1H, m, J=2 與 8)，7.39(1H，m)，7.27-7.15(2H, m), 6.81(1H, d, J=8), 6.73(1H, dd, J=2 與 8)，6.72(1H，d，J=2), 4.37(2H, t, J=6.5), 3.89(3H, s), 3.87(3H, s), 2.64 (2H, t, J=7.3), 1.86(2H, m), 1.78(2H, m) (13CNMR, CDCI3, 100M) δ ： 156.4(d, J=255), 155.8, 149.3, 148.8, 147.2, 134.1, 130.2(d, J=8), 126.8, 124.6(d, J=4), 122.9(d, J=12), 120.1, 117.0(d, J=19), 111.5, 111.1, 71.4, 55.9, 55.8, 34.8, 27.8, 27.3 3-(2,4-二氟苯基)-5-(4-(3,4-二曱氧基苯基)丁氧基)-1,3,4-呋二唑 -2(3H)_ 酮 (^NMR, CDCI3, 400M) δ ： 7.48(1H, m, J=5.9 與 8.5), 7.03-6.94(2H, m)，6.81 (1H，d, J=8), 6.72(1H, dd，J=2 與 8)， 6.71(1H, d, J=2), 4.35(2H, t, J=6.5), 3.88(3H, s), 3.87(3H, s), 2.63(2H, t, J=7.3), 1.86(2H, m), 1.77(2H, m) (13CNMR, CDCI3, 100Μ)δ ： 162.5(dd, J=10.5 與 252)，157.0(dd，J=13 與 258)， 155.8, 149.3, 148.8, 147.2, 134.0, 128.2 (dd,J=1.5 與 10.5), 120.1，119.4(dd,J=4 與 12)，111.9(dd, J=4 與 23)，111.5， 111.1，105.4(dd，J=22.5 與 26.5)，71.4， 58.9, 58.8, 34.8, 27.8, 27.3 3-(4-氣-2-氟笨基)-5-(4-(3,4-二曱氧基苯基)丁氧基)-1，3,4-呋二唑 _2(3H)-酮 ('HNMR, CDCI3, 400M) δ ： 7.44(1H, t, J=7.9), 7.25(1H, d, J=10.5), 7.22(1H, m), 6.80(1H, d, J=7.9), 6.72(1H, dd, J=2 與 7.9)，6.71(1H, br), 4.35(2H, t, J=6.5), 3.88(3H, s), 3.86(3H, s), 2.63(2H, t, J=7.5), 1.85(2H, m), 1.76(2H, m) (13CNMR, CDCI3, 100M) δ ： 156.0(d, J=258), 155.8, 149.0, 148.8, 147.2, 135.l(d, J=9), 134.0, 127.3, 125.0(d, J=4), 121.8(d, J=12), 120.1, 117.8(d, J=22.5), 111.5, 111.1, 71.5, 55.9, 55.8, 34.9, 27.8, 27.3 109 200932732 3-(3-氣-2-氟苯基)-5-(4-(3,4-二甲氧基苯基)丁氧基)-1,3,4-呋二唑 -2(3H)-酮 (•HNMR, CDC13, 400M) δ ： 7.44(2H, m), 7.18(1H, dt，J=1.7 與 8.1)，6·81(1Η, d, J=8)，6·73(1Η, dd, J=2 與 8)，6·72(1Η， br), 4.37(2H, t, J=6.3), 3.89(3H, s), 3.87(3H, s), 2.64(2H, t, J=7.4), 1.87(2H, m), 1.77(2H, m) (13CNMR, CDCI3, 100M) δ ： 155.8, 152.3(d, J=257), 149.0, 148.8, 147.2, 134.0, 130.5, 124.8, 124.5(d, J=5), 124.3(d, J=ll, 122.8(d, J=16), 120.1, 111.5, 111.1, 71.6, 55.9, 55.8, 34.8, 27.8, 27.3 3-(2-氟苯基)-5-(4-(4-氟苯基) 基)-1,3,4-呋二唑-2(3H)-酮 (*HNMR, CDCI3, 400M) δ ： 7.50( 1H, dt, J=2 與 8.3), 7.39( 1H, m), 7.27-7.19(2H， m)，7.14(2H，m, J=5.5 與 8·5), 6.98(2H， m, J=8.7), 4.36(2H, t, J=6.4), 2.66(2H, t, J=7.5), 1.85(2H, m), 1.77(2H, m) (13CNMR, CDCI3, 100Μ)δ ： 161.3(d, J=243), 156.4(d, J=255), 155.7, 149.3, 137.1(d, J=3), 130.2(d, J=8), 129.7(d, J=8), 126.8, 124.6(d, J=4), 122.9(d, J=11.5), 117.1(d, J=19.5), 115.1(d, 1=21.5),71.3,34.4, 27.7,27.3 3-(4-氯-2-氟笨基)-5-(4-經基苯氧基)-1,3,4-呋二唑-2(3H)-酮 ('HNMR, CDCI3, 400M) δ ： 7.42( 1H, t, J=8), 7.25(1H，dd, J=2.3 與 9.9), 7.23-7.18 (3H, m), 6.87(2H, m, J=9), 5.16(1H, s) (13CNMR, CDCI3, 100M) 6 ： 156.1(d, J=259), 155.3, 154.2, 148.9, 144.8, 135.5(d, J=9.5), 127.6, 125.0(d, J=4), 120.9, 117.8(d, J=22.5), 116.4 3-(3-氣-2-氟苯基)-5-(4_經基苯氧基)-1,3,4-呋二唑-2(3H)-嗣 (^NMR, CDCI3, 400M) δ ： 7.43(1H, m), 7.40(1H, m), 7.23(2H, m, J=9), 7.15(1H, dt，J=1.5 與 8), 6.86(2H, m, J=9), 5.36 (1H, s) (13CNMR, CDCI3, 100M) δ ： 155.3, 154.2, 152.5(d, J=257), 148.9, 144.9, 130.9, 125.2, 124.5(d, J=5), 124.0(d, J=12), 122.7(d, J=16), 120.9, 116.4(13CNMR, CDC13, 100M) δ: 156.0, 154.6 (d, J=255), 148.8, 142.0, 129.8 (d, J=7.5), 129.5 (d, J=4), 128.4, 128.3, 126.3, 125.8, 124.0, 118.2 (d, J=21), 71.7, 35.7, 30.9, 28.2, 25.1 5-(4-(3,4-dimethoxyphenyl)butoxy)-3-(2-fluorophenyl) -1,3,4-furadiazole-2(3H)-one ('HNMR, CDCI3, 400M) δ: 7.51 (1H, m, J=2 and 8), 7.39 (1H, m), 7.27- 7.15(2H, m), 6.81(1H, d, J=8), 6.73(1H, dd, J=2 and 8), 6.72(1H,d,J=2), 4.37(2H, t, J= 6.5), 3.89(3H, s), 3.87(3H, s), 2.64 (2H, t, J=7.3), 1.86(2H, m), 1.78(2H, m) (13CNMR, CDCI3, 100M) δ : 156.4(d, J=255), 155.8, 149.3, 148.8, 147.2, 134.1, 130.2(d, J=8), 126.8, 124.6(d, J=4), 122.9(d, J=12), 120.1, 117.0 (d, J=19), 111.5, 111.1, 71.4, 55.9, 55.8, 34.8, 27.8, 27.3 3-(2,4-difluorophenyl)-5-(4-(3,4-dioxyloxy) Phenyl)butoxy)-1,3,4-furadiazole-2(3H)-one (^NMR, CDCI3, 400M) δ: 7.48 (1H, m, J=5.9 and 8.5), 7.03- 6.94(2H, m), 6.81 (1H, d, J=8), 6.72(1H, dd, J=2 and 8), 6.71(1H, d, J=2), 4.35(2H, t, J= 6.5), 3.88(3H, s), 3.87(3H, s), 2.63(2H, t, J=7.3), 1.86(2H, m), 1.77(2H, m) (13CNMR, CDCI3, 100Μ) δ : 162.5 (dd, J=10.5 and 252), 157.0 (dd, J=13 and 258), 155.8 , 149.3, 148.8, 147.2, 134.0, 128.2 (dd, J=1.5 and 10.5), 120.1, 119.4 (dd, J=4 and 12), 111.9 (dd, J=4 and 23), 111.5, 111.1, 105.4 ( Dd, J = 22.5 and 26.5), 71.4, 58.9, 58.8, 34.8, 27.8, 27.3 3-(4-Ga-2-fluorophenyl)-5-(4-(3,4-dimethoxyphenyl) Butoxy)-1,3,4-furadiazole-2(3H)-one ('HNMR, CDCI3, 400M) δ: 7.44 (1H, t, J=7.9), 7.25(1H, d, J =10.5), 7.22(1H, m), 6.80(1H, d, J=7.9), 6.72(1H, dd, J=2 and 7.9), 6.71(1H, br), 4.35(2H, t, J= 6.5), 3.88(3H, s), 3.86(3H, s), 2.63(2H, t, J=7.5), 1.85(2H, m), 1.76(2H, m) (13CNMR, CDCI3, 100M) δ : 156.0(d, J=258), 155.8, 149.0, 148.8, 147.2, 135.l(d, J=9), 134.0, 127.3, 125.0(d, J=4), 121.8(d, J=12), 120.1, 117.8 (d, J=22.5), 111.5, 111.1, 71.5, 55.9, 55.8, 34.9, 27.8, 27.3 109 200932732 3-(3-Actyl-2-fluorophenyl)-5-(4-(3, 4-Dimethoxyphenyl)butoxy)-1,3,4-furadiazole-2(3H)-one (•HNMR, CDC13, 400M) δ : 7.44(2H, m ), 7.18 (1H, dt, J=1.7 and 8.1), 6.81 (1Η, d, J=8), 6.73 (1Η, dd, J=2 and 8), 6.72 (1Η, br ), 4.37(2H, t, J=6.3), 3.89(3H, s), 3.87(3H, s), 2.64(2H, t, J=7.4), 1.87(2H, m), 1.77(2H, m (13CNMR, CDCI3, 100M) δ: 155.8, 152.3 (d, J=257), 149.0, 148.8, 147.2, 134.0, 130.5, 124.8, 124.5 (d, J=5), 124.3 (d, J=ll, 122.8 (d, J=16), 120.1, 111.5, 111.1, 71.6, 55.9, 55.8, 34.8, 27.8, 27.3 3-(2-fluorophenyl)-5-(4-(4-fluorophenyl)yl) -1,3,4-furadiazole-2(3H)-one (*HNMR, CDCI3, 400M) δ : 7.50 ( 1H, dt, J=2 and 8.3), 7.39 ( 1H, m), 7.27-7.19 (2H, m), 7.14 (2H, m, J=5.5 and 8·5), 6.98(2H, m, J=8.7), 4.36(2H, t, J=6.4), 2.66(2H, t, J =7.5), 1.85(2H, m), 1.77(2H, m) (13CNMR, CDCI3, 100Μ)δ : 161.3(d, J=243), 156.4(d, J=255), 155.7, 149.3, 137.1( d, J=3), 130.2(d, J=8), 129.7(d, J=8), 126.8, 124.6(d, J=4), 122.9(d, J=11.5), 117.1(d, J =19.5), 115.1 (d, 1 = 21.5), 71.3, 34.4, 27.7, 27.3 3-(4-chloro-2-fluorophenyl)-5-(4-phenylphenoxy)-1,3, 4-furadiazole-2(3H)-one ('HNMR, CDCI3, 400M) δ : 7.42 ( 1H, t, J=8 ), 7.25 (1H, dd, J=2.3 and 9.9), 7.23-7.18 (3H, m), 6.87 (2H, m, J=9), 5.16(1H, s) (13CNMR, CDCI3, 100M) 6 : 156.1(d, J=259), 155.3, 154.2, 148.9, 144.8, 135.5(d, J=9.5), 127.6, 125.0(d, J=4), 120.9, 117.8(d, J=22.5), 116.4 3 -(3-Gas-2-fluorophenyl)-5-(4-diphenylphenoxy)-1,3,4-furadiazole-2(3H)-嗣(^NMR, CDCI3, 400M) δ : 7.43(1H, m), 7.40(1H, m), 7.23(2H, m, J=9), 7.15(1H, dt, J=1.5 and 8), 6.86(2H, m, J=9), 5.36 (1H, s) (13CNMR, CDCI3, 100M) δ : 155.3, 154.2, 152.5(d, J=257), 148.9, 144.9, 130.9, 125.2, 124.5(d, J=5), 124.0(d, J =12), 122.7(d, J=16), 120.9, 116.4

依據下列方法測定試管中的FAAH活性：使用冰凍的威士塔(wistar)大鼠腦部（無小腦），將各腦 110 200932732 置於15毫升的ImM氣化鎂、酸鹼值為7_0的20nM HEPES 中，及以波特愛維瀚(PotterElvejhem)均化器進行均化作用 (於500 rpm打擊8次）。均化產物於4°C以36000g離心20分鐘 (貝克曼(Beckman) 70Ti型旋轉器）。將片狀沈澱物再度懸浮 5 於b毫升的相同缓衝液中，及在相同條件下離心。將片狀沈澱物再度懸浮於15毫升的相同緩衝液中，及於37°C培養 15分鐘，之後於4°C以36000g離心20分鐘。然後將各片狀沈澱物再度懸浮15毫升的3mM氯化鎂、ImMEDTA、酸鹼值為 © 7.4的5〇mM Tris及蛋白質中’該蛋白質係使用BSA(50-250 10 微克/毫升）的一標準曲線而以BioRad蛋白質分析(BioRad) 測定之。將膜懸浮液分量，及儲存於_8〇°C。使用AEA(以3H標記該分子的乙醇胺部份)作為受質及測量所形成的3H-乙醇胺，而測定faah活性。反應混合物 (總體積為200微升)含有：2μΜ ΑΕΑ (2μΜ AEA + 5 nM 3H-15 AEA)、〇·1%無脂肪酸的BSA、位於imM EDTA中的5微克的蛋白質、酸鹼質為7·6的10mM Tris及1〇 μΜ或100 mM化合 ® 物。在100% DMS0中製備待試驗化合物（10 mM)的貯備液，而分析中所用的DMSO濃度為0.1%。在37°c預培養15 分鐘之後’藉由添加受質溶液（冷的EAE+經放射線標記的 2〇 EAE + BSA)而起始反應。反應進行1〇分鐘，然後藉由添加 400微升活性碳懸浮液（位於32毫升的〇·5Μ鹽酸中之8克的炭及處於連續授摔狀態）’而終止反應。在授拌作用下，在室溫中培養30分鐘之後，藉由在微量離心機中的離心作用 (於13000 rpm離心10分鐘），將炭沈澱。在先行置入24槽式 111 200932732 平皿中的800微升Optiphase Supermix閃爍液中，添加2〇〇微升的上清液。在Microbeta TriLux閃爍計數器中（計數丨〇分鐘或直至σ=2)，測定每分鐘計數值(cpm)。在各分析中，均有空白組（無蛋白質，通常低於200 cpm) 5 及對照組（無化合物）。結果以減去空白組後的對照組％，示於第3表中。第3表化合物 FAAHi 活性（％ ΙΟΟηΜ劑量鉍對照組） 5-(节氧基)-3_(3_氣苯基)-1，3,4·呋二唑-2(3H)-酮 8.6 3-(4-漠苯基)-5-苯氧基-1，3,4-咬二嗤-2(311)-8¾ 24.81 3-(3'-甲氧基聯苯基-4-基)-5-笨氧基-1，3,4-呋二唑 -2(3H)-酮 11.63 5-(节氧基)_3_對-甲笨基-1，3,4_吱二。坐-2(3H)-酮 44.47 5-(节氧基)-3_(4_甲氧基笨基)-1，3,4-吱二唑-2(3H)-酮 12.67 5-(节氧基)-3-(2-氟苯基)-1，3,4-咬二嗤-2(3H)-酮 3.52 5-(节氧基)-3-(4-氰基笨基)-1,3,4-呋二唑-2(311)-明 19.3 3-(4-氰基苯基)-5-苯氧基-1，3,4-吱二吐-2(3H)-酮 95.63 5-(节氧基)-3-(2,5-二曱基苯基)-i,3,4-吱二哇-2(3H)-酮 59.02 5-(节氧基)-3-(3-硝基笨基)-1，3,4-"夫二。坐-2(3H)-鋼 21.28 3-(3-硝基苯基)-5-苯氧基-l，3,4-咬二峻-2(3H)-網 78.36 3-(4-甲氧基苯基)-5-苯氧基-i，3,4-口夫二口坐-2(3H)-酮 18.49 5-(节氧基)-3-苯基-1，3,4-呋二吐-2(3H)·酮 21.19 3-(4-經基苯基)-5-苯氧基-i,3,4_吱二唾_2(3H)-酮 28.39 5-苯氧基-3-苯基·1，3,4-吱二峻-2(3H)-嗣 55.64 5-苯氧基-3-(4中比咬-3-基)苯基)-i，3,4-呋二唑-2(3H)-酮 12.2 3-(聯笨基_4_基)-5-苯氧基_1，3,4_吱二唾-2(3H)-酮 16.59 '一 T氧基聯笨基-4·-基)-5-苯氧基-1，3,4-咬二0坐 -2(3H)-嗣 12.68 5-(苄氧基)-3-(4-特-丁基苯基)_ι,3,4-吱二峻-2(3H)-酮 34.6 氧基)-3-(4-’;臭笨基)-1，3,4-〇夫二》坐-2(3H)-酮 8.01 3-(4-溴苯基)-5-(4-硝基苯氧基)_ 1，3,4-呋二唑-2(3H)-酮 7.3 3-(3-氣苯基)-5-(4-硝基笨氧基)_ι，3,4—吱二唆-2(311)-酮 9.1 200932732The FAAH activity in the test tube was determined according to the following method: Using the frozen Wistar rat brain (without the cerebellum), each brain 110 200932732 was placed in 15 ml of 1 mM magnesium sulfide, 20 nM having a pH of 7_0. Homogenization in HEPES and with a Potter Elvejhem homogenizer (8 hits at 500 rpm). The homogenized product was centrifuged at 36000 g for 20 minutes at 4 ° C (Beckman 70 Ti type rotator). The pellet was resuspended in b ml of the same buffer and centrifuged under the same conditions. The pellet was resuspended in 15 ml of the same buffer and incubated at 37 ° C for 15 minutes, followed by centrifugation at 36000 g for 20 minutes at 4 ° C. The pellets were then resuspended in 15 ml of 3 mM magnesium chloride, 1 mM EDTA, 5 mM Tris with a pH of 7.4, and a standard curve for the protein using BSA (50-250 10 μg/ml). It was determined by BioRad Protein Assay (BioRad). The membrane suspension fraction was stored at _8 °C. The faah activity was determined using AEA (labeling the ethanolamine moiety of the molecule with 3H) as the substrate and measuring the formed 3H-ethanolamine. The reaction mixture (total volume of 200 μl) contained: 2 μΜ ΑΕΑ (2 μΜ AEA + 5 nM 3H-15 AEA), 〇·1% fatty acid-free BSA, 5 μg protein in imM EDTA, pH 7 • 6 mM Tris and 1 μM or 100 mM Compound®. A stock solution of the test compound (10 mM) was prepared in 100% DMS0, and the concentration of DMSO used in the analysis was 0.1%. After pre-incubation for 15 minutes at 37 ° C, the reaction was initiated by the addition of a substrate solution (cold EAE + radiolabeled 2 〇 EAE + BSA). The reaction was carried out for 1 minute, and then the reaction was terminated by adding 400 μl of an activated carbon suspension (8 g of charcoal in 32 ml of 〇·5 Μ hydrochloric acid and in a continuous dropping state). After incubation for 30 minutes at room temperature, the carbon was precipitated by centrifugation in a microcentrifuge (centrifugation at 13,000 rpm for 10 minutes). Add 2 μl of the supernatant to the 800 μl Optiphase Supermix scintillation fluid in a 24-well 111 200932 32 dish. The count per minute (cpm) was determined in a Microbeta TriLux scintillation counter (count 丨〇 min or until σ = 2). In each analysis, there was a blank group (no protein, usually less than 200 cpm) 5 and a control group (no compound). The results are shown in Table 3 after subtracting the % of the control group after the blank group. Compound No. 3 FAAHi activity (% ΙΟΟηΜ dose 铋 control group) 5-(hydroxyl)-3_(3_ phenyl)-1,3,4·furadiazole-2(3H)-one 8.6 3- (4-Molyphenyl)-5-phenoxy-1,3,4-bitidin-2(311)-83⁄4 24.81 3-(3'-Methoxybiphenyl-4-yl)-5 -Phenoxy-1,3,4-furadiazole-2(3H)-one 11.63 5-(hydroxy)_3_p-methylidene-1,3,4_吱2. -2(3H)-ketone 44.47 5-(hydroxy)-3_(4-methoxyphenyl)-1,3,4-oxadiazole-2(3H)-one 12.67 5-(oxygen) 3-(2-fluorophenyl)-1,3,4-dioxa-2(3H)-one 3.52 5-(oxy)-3-(4-cyanophenyl)-1 , 3,4-furadiazole-2(311)- Ming 19.3 3-(4-cyanophenyl)-5-phenoxy-1,3,4-anthracene-2(3H)-one 95.63 5-(hydroxy)-3-(2,5-diamidinophenyl)-i,3,4-fluorenyl-2(3H)-one 59.02 5-(hydroxy)-3-( 3-nitro stupid)-1,3,4-" Fu II. Sitting -2 (3H)-steel 21.28 3-(3-nitrophenyl)-5-phenoxy-l,3,4-biting two-jun-2(3H)-net 78.36 3-(4-methoxy Phenyl)-5-phenoxy-i,3,4-mouth 2 bis-(3H)-one 18.49 5-(oxy)-3-phenyl-1,3,4-furan Dioxa-2(3H)·ketone 21.19 3-(4-Phenylphenyl)-5-phenoxy-i,3,4_indole disal_2(3H)-one 28.39 5-phenoxy- 3-phenyl·1,3,4-anthracene-2(3H)-嗣55.64 5-phenoxy-3-(4-indolyl-3-yl)phenyl)-i,3,4- Furadiazole-2(3H)-one 12.2 3-(Lianthyl-4-yl)-5-phenoxy_1,3,4_吱disin-2(3H)-one 16.59 '-T-oxygen基基基基-4·-yl)-5-phenoxy-1,3,4-bito 2 sitting-2(3H)-嗣12.68 5-(benzyloxy)-3-(4-spec- Butylphenyl)_ι,3,4-indenyl-2(3H)-one 34.6 oxy)-3-(4-'; stinky)-1,3,4-coin 2 sitting- 2(3H)-ketone 8.01 3-(4-bromophenyl)-5-(4-nitrophenoxy)_ 1,3,4-furadiazole-2(3H)-one 7.3 3-(3 - gas phenyl)-5-(4-nitrophenyloxy)_ι,3,4-quinone-2(311)-ketone 9.1 200932732

5-(4-氣苯氧基)-3-苯基-1,3,4-呋二唑-2(3H)-酮 30.9 3-(3-溴苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 62.21 3-(聯苯基-3-基)-5-苯氧基-1,3,4-呋二唑-2(311)-酮 32.01 5-苯氧基-3-(3-(吡啶-3-基)苯基)-1，3,4-呋二唑-2(3H)-酮 19.52 5-(4-曱氧基苯氧基)-3-苯基-1，3,4-呋二唑-2(3H)-酮 7.44 5-(节氧基)-3-(3-漠苯基)-1,3,4-呋二唑-2(3H)-酮 8.67 5-(4-(节氧基)苯氧基)-3-苯基-1,3,4-呋二唑-2(3H)-酮 18.24 3-(5'甲氧基聯苯基-3-基)-5-苯氧基-1,3,4-呋二唑 -2(3H)-酮 27.58 5-(苄氧基)-3-(聯苯基-3-基)-1,3,4-呋二唑-2(3H)-酮 12.74 5-(节氧基)-3-(3’-甲氧基聯苯基-3-基)-1，3,4-呋二唑 -2(3H)-酮 9.41 5-(4-氣苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 0.64 3-(4’-氰基聯苯基-3-基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 6.27 3-(2-氟苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 3.37 3-(3'-氰基聯苯基-3-基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 19.29 3-W-氰基聯苯基-4-基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 13.52 5-(4-氣苯氧基)-3-(2,4-二氟苯基)-1,3,4-呋二唑-2(3H)-酮 1.75 5-(节氧基)-3-(2,5-二氟苯基)-1，3,4-呋二唑-2(311)-酮 1.12 3-(2,5-二氟苯基)-5-苯氧基-1，3,4-呋二唑-2(3H)-酮 2.35 3-(2-氟苯基)-5-(4-甲氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 0.29 5-(苄氧基)-3-(2,4-二氟苯基)-1，3,4-呋二唑-2(3H)-酮 4.4 3-(2-氟苯基)-5-(4-硝基苯氧基)-1,3,4-呋二唑-2(3H)-酮 4.48 5-(4-氯苯氧基)-3-(2,5-二氟苯基)-1,3,4-呋二唑-2(3H)-酮 5.57 5-(4-氣苯氧基)-3-(3’，4’-二甲氧基聯苯基-3-基)-1,3,4-呋二唑-2(3H)-酮 0.3 3-(3-溴苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑-2(3H)-酮 11.11 3-(2,4-二氟苯基)-5-苯氧基-1，3,4-呋二唑-2(3H)-酮 3.08 3-(2,4-二氟苯基)-5-(萘-1-基氧)-1,3,4-呋二唑-2(3H)-酮 4.77 5-(2-氣苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 1.82 3-(2,4-二氟苯基)-5-(3-(三氟甲基)苯氧基)-1,3,4-呋二唑 -2(3H)-酮 13.35 5-(4-溴苯氧基)-3-(2,5-二氟苯基)-1,3,4-呋二唑-2(3H)-酮 10.87 3-(2,5-二氟苯基)-5-(4-氟苯氧基)-1,3,4-呋二唑-2(3H)-酮 1.85 5-(4-氣苯氧基)-3-(2-甲氧基苯基)-1,3,4-呋二唑-2(3H)-酮 70.37 3-(2-氣苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 32.63 3-(4-溴苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑-2(3H)-酮 11.34 113 200932732 5-(4-氣苯氧基)-3-(4’-乳基聯苯基-3-基)-1，3,4-咬二〇坐 -2(3H)-酮 6.26 5-(2,4-二氟苯氧基)-3-苯基-1,3,4-呋二唑-2(3H)-酮 1.29 3-(3-氣苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑-2(3H)-酮 8.98 5-(2,4-二氟苯氧基)-3-(4-曱氧基苯基)-1，3,4-呋二唑 -2(3H)-酮 0.26 5-(4-氣苯氧基)-3-(3VT-二甲氧基聯苯基-4-基)-1,3,4-呋二唑-2(3H)-酮 28.79 3-(5-溴-2-氟苯基)-5-(4-甲氧基苯氧基)-1,3,4-呋二唑 -2(3H)-酮 0.71 3-(4-氟-4\5’-二甲氧基聯苯基-3-基)-5-(4-甲氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 0.54 3-(3-溴苯基)-5-(4-甲氧基笨氧基)-1,3,4-呋二唑-2(3H)-酮 17.69 3-(4-溴苯基)-5-(4-甲氧基苯氧基)-1，3,4-呋二唑-2(3H)-酮 8.28 3-(4-氟苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 23.33 5-(4-氣苯乳基)-3-(4-乱_4'，5’_二曱氧基聯苯基-3-基)-1,3,4-呋二唑-2(311)-酮 2.43 3_(2-氟冰(0比咬基)苯基)-5-(4_甲氧基苯氧基)-1，3,4-11 夫二 σ坐-2(3H)-網 0.73 3-(3-氟_4'，5'_二曱氧基聯苯基-4-基)-5-(4-曱氧基苯氧基)-1,3,4-呋二唑-2(3H)-酮 0.6 3-(3-氟-4’-氰基聯苯基-4-基)-5-(4-曱氧基苯氧基)-1,3,4 -σ夫二 °^-2(3H)-嗣 2.23 3-(4-氟苯基)-5-(4-甲氧基苯氧基)-1，3,4-呋二唑-2(3H)-酮 2.57 3-(4-氣-2-氟苯基)-5-(4-甲氧基苯氧基)-1，3,4-呋二唑 -2(3H)-酮 1.07 5-(4-曱氧基苯氧基)-3-(4-曱氧基苯基)-1,3,4-呋二唑 -2(3H)-酮 1.19 5-(4-氣苯氧基)-3-(4-甲氧基苯基)-1,3,4-呋二唑-2(3H)-酮 1.04 3-(4'-(二甲基胺基)-3-氣聯苯基-4-基)-5-(4-甲氧基苯氧基)-1，3,4-呋二唑-2(3H)-酮 5.55 5-(4-氣苯氧基)-3-(4-羥基苯基)-1，3,4-呋二唑-2(3H)-酮 0.56 3-(4-溴苯基)-5-(2,4-二氟苯氧基)-1,3/t-呋二唑-2(3H)-酮 4.41 5-(4-溴-2-甲氧基苯氧基)-3-苯基-1,3,4-呋二唑-2(3H)-酮 1.43 5-(3,5-二甲氧基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑 -2(3H)-酮 5.99 5-(4-氰基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 1.88 3-(2-氟苯基)-5-(萘-2-基氧)-1,3,4-呋二唑-2(3H)-酮 3.03 3-苯基-5-(吡啶-3-基氧)-1,3,4-呋二唑-2(3H)-酮 46.52 3-(5-溴-2-氟苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑-2(3H)-酮 11.63 5-(4-氟苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 2.32 5-(3,4-二甲氧基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑 -2(3H)-酮 14.125-(4-Vephenoxy)-3-phenyl-1,3,4-furadiazole-2(3H)-one 30.9 3-(3-bromophenyl)-5-phenoxy-1 , 3,4-furadiazole-2(3H)-one 62.21 3-(biphenyl-3-yl)-5-phenoxy-1,3,4-furadiazole-2(311)-one 32.01 5-Phenoxy-3-(3-(pyridin-3-yl)phenyl)-1,3,4-furadiazole-2(3H)-one 19.52 5-(4-decyloxyphenoxy Benzyl-3-phenyl-1,3,4-furadiazole-2(3H)-one 7.44 5-(hydroxy)-3-(3-indolyl)-1,3,4-furan Diazole-2(3H)-one 8.67 5-(4-(hydroxy)phenoxy)-3-phenyl-1,3,4-furadiazole-2(3H)-one 18.24 3-( 5'Methoxybiphenyl-3-yl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 27.58 5-(benzyloxy)-3-(biphenyl 3-yl)-1,3,4-furadiazole-2(3H)-one 12.74 5-(hydroxy)-3-(3'-methoxybiphenyl-3-yl)- 1,3,4-furadiazole-2(3H)-one 9.41 5-(4-phenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2 ( 3H)-ketone 0.64 3-(4'-Cyanobiphenyl-3-yl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 6.27 3-(2- Fluorophenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 3.37 3-(3'-cyanobiphenyl-3-yl)-5-phenoxy -1,3,4-furadiazole-2(3H)-one 19.29 3-W-cyanobiphenyl-4-yl)-5-phenoxy -1,3,4-furadiazole-2(3H)-one 13.52 5-(4-phenoxy)-3-(2,4-difluorophenyl)-1,3,4-furo Azole-2(3H)-one 1.75 5-(hydroxy)-3-(2,5-difluorophenyl)-1,3,4-furadiazole-2(311)-one 1.12 3-( 2,5-difluorophenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 2.35 3-(2-fluorophenyl)-5-(4-methoxy Phenoxy)-1,3,4-furadiazole-2(3H)-one 0.29 5-(benzyloxy)-3-(2,4-difluorophenyl)-1,3,4- Furadiazole-2(3H)-one 4.4 3-(2-fluorophenyl)-5-(4-nitrophenoxy)-1,3,4-furadiazole-2(3H)-one 4.48 5-(4-Chlorophenoxy)-3-(2,5-difluorophenyl)-1,3,4-furadiazole-2(3H)-one 5.57 5-(4-phenoxy) )-3-(3',4'-dimethoxybiphenyl-3-yl)-1,3,4-furadiazole-2(3H)-one 0.3 3-(3-bromophenyl) 5-(4-phenoxy)-1,3,4-furadiazole-2(3H)-one 11.11 3-(2,4-difluorophenyl)-5-phenoxy-1, 3,4-furadiazole-2(3H)-one 3.08 3-(2,4-difluorophenyl)-5-(naphthalen-1-yloxy)-1,3,4-furadiazole-2 (3H)-keto 4.77 5-(2-phenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 1.82 3-(2,4 -difluorophenyl)-5-(3-(trifluoromethyl)phenoxy)-1,3,4-furadiazole-2(3H)-one 13.35 5-(4-bromophenoxy) -3- (2,5-difluorophenyl)-1,3,4-furadiazole-2(3H)-one 10.87 3-(2,5-difluorophenyl)-5-(4-fluorophenoxy -1,3,4-furadiazole-2(3H)-one 1.85 5-(4-phenoxy)-3-(2-methoxyphenyl)-1,3,4-furo Azole-2(3H)-one 70.37 3-(2-phenylphenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 32.63 3-(4-bromophenyl -5-(4-Vephenoxy)-1,3,4-furadiazole-2(3H)-one 11.34 113 200932732 5-(4-Vephenoxy)-3-(4'-milk Benzyl-3-yl)-1,3,4-didentate-2(3H)-one 6.26 5-(2,4-difluorophenoxy)-3-phenyl-1,3 , 4-furadiazole-2(3H)-one 1.29 3-(3-phenylphenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2 ( 3H)-keto 8.98 5-(2,4-difluorophenoxy)-3-(4-decyloxyphenyl)-1,3,4-furadiazole-2(3H)-one 0.26 5- (4-Vephenoxy)-3-(3VT-dimethoxybiphenyl-4-yl)-1,3,4-furadiazole-2(3H)-one 28.79 3-(5-bromo -2-fluorophenyl)-5-(4-methoxyphenoxy)-1,3,4-furadiazole-2(3H)-one 0.71 3-(4-fluoro-4\5'- Dimethoxybiphenyl-3-yl)-5-(4-methoxyphenoxy)-1,3,4-furadiazole-2(3H)-one 0.54 3-(3-bromobenzene 5-(4-methoxyphenyloxy)-1,3,4-furadiazole-2(3H)-one 17.69 3-(4-bromo Phenyl)-5-(4-methoxyphenoxy)-1,3,4-furadiazole-2(3H)-one 8.28 3-(4-fluorophenyl)-5-phenoxy- 1,3,4-furadiazole-2(3H)-one 23.33 5-(4-gasophenyl)-3-(4- disorder _4',5'-dioxaoxybiphenyl-3 -yl)-1,3,4-furadiazole-2(311)-one 2.43 3_(2-fluoro-ice (0-bito)phenyl)-5-(4-methoxyphenoxy)- 1,3,4-11 Fushuang sigma sitting-2(3H)-net 0.73 3-(3-Fluoro-4',5'-dioxaoxybiphenyl-4-yl)-5-(4- Nonylphenoxy)-1,3,4-furadiazole-2(3H)-one 0.6 3-(3-Fluoro-4'-cyanobiphenyl-4-yl)-5-(4 -decyloxyphenoxy)-1,3,4-oxadol-2(3H)-嗣2.23 3-(4-fluorophenyl)-5-(4-methoxyphenoxy) -1,3,4-furadiazole-2(3H)-one 2.57 3-(4-Gas-2-fluorophenyl)-5-(4-methoxyphenoxy)-1,3,4 -furadiazole-2(3H)-one 1.07 5-(4-decyloxyphenoxy)-3-(4-decyloxyphenyl)-1,3,4-furadiazole-2 (3H )-ketone 1.19 5-(4-Vephenoxy)-3-(4-methoxyphenyl)-1,3,4-furadiazole-2(3H)-one 1.04 3-(4'- (Dimethylamino)-3-cyclobiphenyl-4-yl)-5-(4-methoxyphenoxy)-1,3,4-furadiazole-2(3H)-one 5.55 5-(4-Vephenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2 (3 H)-ketone 0.56 3-(4-bromophenyl)-5-(2,4-difluorophenoxy)-1,3/t-furadiazole-2(3H)-one 4.41 5-(4 -Bromo-2-methoxyphenoxy)-3-phenyl-1,3,4-furadiazole-2(3H)-one 1.43 5-(3,5-dimethoxyphenoxy) -3-(2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 5.99 5-(4-cyanophenoxy)-3-(2-fluorophenyl)- 1,3,4-furadiazole-2(3H)-one 1.88 3-(2-fluorophenyl)-5-(naphthalen-2-yloxy)-1,3,4-furadiazole-2 ( 3H)-keto 3.03 3-phenyl-5-(pyridin-3-yloxy)-1,3,4-furadiazole-2(3H)-one 46.52 3-(5-bromo-2-fluorophenyl -5-(4-Vephenoxy)-1,3,4-furadiazole-2(3H)-one 11.63 5-(4-fluorophenoxy)-3-(4-hydroxyphenyl) -1,3,4-furadiazole-2(3H)-one 2.32 5-(3,4-dimethoxyphenoxy)-3-(2-fluorophenyl)-1,3,4- Furadiazole-2(3H)-one 14.12

114 200932732114 200932732

5-(2,4-二氟苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑 -2(3H)-酮 0.31 3-(2-氟-4-(甲基磺醯基)苯基)-5-(4-甲氧基苯氧基)-1，3,4-呋二唑-2(3印-酮 0.21 5-(4-氟苯氧基)-3-(4-甲氧基苯基)-1,3,4-呋二唾-2(3H)-_ 2.08 5-(聯苯基-4-基氧)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 1.03 3-(2-氟苯基)-5-(3,4,5-三曱氧基苯氧基)-1,3,4-呋二唑 -2(3H)-酮 69.17 3-(4-甲氧基苯基)-5-(3-(三氟甲基)苯氧基)-1,3,4-呋二唑-2(3H)-酮 3.49 3-(4-曱氧基苯基)-5-(對-曱苯基氧)-1,3,4-呋二唑 -2(3H)-酮 4.24 3-(4-羥基苯基)-5-(對-曱苯基氧)-1,3,4-呋二唑-2(3H)-酮 1.23 3-(3-氣-2-氟苯基)-5-(4-甲氧基苯氧基)-1,3,4-呋二唑 -2(3H)-酮 0.67 3-(4-羥基苯基)-5-(3-(三氟曱基)苯氧基)-1，3,4-呋二唑 -2(3H)-酮 1.07 5-(苄氧基)-3-(3-氟苯基)-1,3,4-呋二唑-2(3H)-酮 12.15 3-(3-氟苯基)-5-(4-甲氧基苯氧基)-1,3,4-呋二峻-2(3H)-嗣 10.52 5-(3,5-二羥基苯氧基)-3-(2-氟苯基)-1，3,4-呋二唑 -2(3H)-酮 1.08 3-(4-曱氧基苯基)-5-(吡啶-3-基氧)-1,3,4-呋二唑-2(3H)-酮 28.19 5-(2-氣-4-羥基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑 -2(3H)-酮 1.93 3-(5-氣-2-氟苯基)-5-(4-甲氧基苯氧基)-1,3,4-呋二唑 -2(3H)-酮 0.92 3-(4-羥基苯基)-5-(4-硝基苯氧基)-1,3,4-呋二唑-2(3H)-酮 0.42 5-(2,4-二氣苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑 -2(3H)-酮 0.38 3-(2-氟苯基)-5-(3-羥基苯氧基)-1,3,4-呋二唑-2(3H)-酮 11.39 3-(2-氟苯基)-5-(吡啶-3-基氧)-1,3,4-呋二唑-2(3H)-酮 38.39 3-(2,4-二氟苯基)-5-(吡啶-3-基氧)-1,3,4-呋二唑-2(3H)-酮 48.57 3-(2-氟-4-(甲基磺醯基)苯基)-5-(吡啶-3-基氧)-1,3,4-呋二唑-2(3H)-酮 15.98 5-(2-溴吼啶-3-基氧)-3-(4-甲氧基苯基)-1,3,4-呋二唑 -2(3H)-酮 3.36 5-(環己氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3印-酮 2.58 3-(3-氣-2-氟苯基)-5-(環己氧基)-1,3,4-呋二唑-2(3H)-酮 13.54 5-(環己氧基)-3-(4-曱氧基苯基)-1,3,4-呋二唑-2(311)-酮 45.11 5-(環己氧基)-3-(3-氟-4’，5’-二甲氧基聯苯基-4-基)-1，3,4-呋二唑-2(3H)-酮 30.3 3-(3-羥基苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 14.04 5-(環己氧基)-3-(3-氟-3'-(三氟甲氧基)聯苯基-4-基)-1,3,4-呋二唑-2(3H)-酮 35.39 115 200932732 5-(4-氣苯氧基)-3-(3-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 1.21 5-(4-氟苯氧基)-3-(3-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 2.95 3-(4-氣-2-氟苯基)-5-苯乙氧基-1,3,4-呋二唑-2(3H)-酮 10.49 3-(4-羥基苯基)-5-笨乙氧基-1,3,4-呋二唑-2(3H)-酮 24.03 3-(2-氟苯基)-5-異丁氧基-1,3,4-呋二唑-2(3H)-酮 11.63 3-(4-羥基苯基)-5-(3-苯基丙氧基)-1,3,4-呋二唑-2(3H)-酮 21.68 3-(4-羥基苯基)-5-(4-苯基丁氧基)-1,3,4-呋二唑-2(3H)-酮 5.49 3-(4-羥基苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑-2(3H)-酮 3.3 3-(4-羥基苯基)-5-(6-苯基己基氧)-1,3,4-呋二唑-2(3H)-酮 13.56 3-(4-胺基續酿基苯基)-5-(4-氣苯乳基)-1，3,4-σ夫二°坐 -2(3Η)-酮 5.16 3-(4-胺基績酿基苯基)-5-(4-甲乳基苯氧基)-1,3,4-咬二唑-2(3Η)-酮 8.32 3-(4-羥基苯基)-5-(2-苯氧基乙氧基)-1,3,4-呋二唑 -2(3Η)-酮 33.2 5-(2-氣苯乙氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3Η)-酮 2.54 3-(4-胺基磺醯基苯基)-5-(4-氣苯氧基)-1，3,4-呋二唑 -2(3Η)-酮 5.89 3-(4-胺基續酿基苯基)-5-苯氧基-1，3,4-呋二唑-2(3Η)-酮 7.61 3-苯基-5-(5-苯基戊基氧)-1，3,4-呋二唑-2(3Η)-酮 47.86 3-(2-氟苯基)-5-(4-苯基丁氧基)-1，3,4-呋二唑-2(3Η)-酮 19.62 3-(4-胺基磺醯基苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑 -2(3Η)-酮 0.09 3-(2-氟苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑-2(3Η)-酮 18.12 3-(2,4-二氟苯基)-5-(5-苯基戊基氧)-1，3,4-吱二唑 -2(3Η)-酮 43.31 5-(4-(3,4-二甲氧基苯基)丁氧基)-3-苯基-1，3,4-呋二唑 -2(3Η)-酮 39.74 3-(2-氣-5-氟苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑 -2(3Η)-酮 9.94 5-(4-(3,4-二甲氧基苯基)丁氧基)-3-(2-氟苯基)-1,3,4-呋二 σ坐 _2(3Η)-嗣 3.85 5-(2-氣苯乙氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3Η)-酮 1.18 3-(2,4-二氟苯基)-5-(4-(3+二曱氧基苯基)丁氧基)-1,3,4-呋二唑-2(311)-酮 6.31 3-(4-氣-2-氟苯基)-5-(4-(3,4-二甲氧基苯基)丁氧基)-1，3,4-呋二唑-2(3Η)-酮 3.17 3-(3-氣-2-氟苯基)-5-(4-(3,4-二甲氧基苯基)丁氧基)-1,3,4-呋二唑-2(311)-酮 22.32 3-(4-胺基羰基苯基)-5-苯氧基-1，3,4-呋二唑-2(3Η)-酮 47.96 3-(4-胺基橫酿基苯基)-5-(4-(3,4-二甲乳基苯基)丁乳基)_1，3,4-呋二唑-2(3Η)-酮 0.095-(2,4-difluorophenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 0.31 3-(2-fluoro-4- (methylsulfonyl)phenyl)-5-(4-methoxyphenoxy)-1,3,4-furadiazole-2 (3-butanone 0.21 5-(4-fluorophenoxy) )-3-(4-methoxyphenyl)-1,3,4-furdisin-2(3H)-- 2.08 5-(biphenyl-4-yloxy)-3-(2-fluoro Phenyl)-1,3,4-furadiazole-2(3H)-one 1.03 3-(2-fluorophenyl)-5-(3,4,5-trimethoxyphenoxy)-1 , 3,4-furadiazole-2(3H)-one 69.17 3-(4-methoxyphenyl)-5-(3-(trifluoromethyl)phenoxy)-1,3,4- Furadiazole-2(3H)-one 3.49 3-(4-decyloxyphenyl)-5-(p-nonylphenyloxy)-1,3,4-furadiazole-2(3H)-one 4.24 3-(4-Hydroxyphenyl)-5-(p-nonylphenyloxy)-1,3,4-furadiazole-2(3H)-one 1.23 3-(3-Gas-2-fluorobenzene 5-(4-methoxyphenoxy)-1,3,4-furadiazole-2(3H)-one 0.67 3-(4-hydroxyphenyl)-5-(3-(three Fluorinyl)phenoxy)-1,3,4-furadiazole-2(3H)-one 1.07 5-(benzyloxy)-3-(3-fluorophenyl)-1,3,4- Furadiazole-2(3H)-one 12.15 3-(3-fluorophenyl)-5-(4-methoxyphenoxy)-1,3,4-furodijun-2(3H)-嗣10.52 5-(3,5-Dihydroxyphenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2(3H)- 1.08 3-(4-decyloxyphenyl)-5-(pyridin-3-yloxy)-1,3,4-furadiazole-2(3H)-one 28.19 5-(2-Ga-4- Hydroxyphenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 1.93 3-(5-Ga-2-fluorophenyl)-5-( 4-methoxyphenoxy)-1,3,4-furadiazole-2(3H)-one 0.92 3-(4-hydroxyphenyl)-5-(4-nitrophenoxy)-1 , 3,4-furadiazole-2(3H)-one 0.42 5-(2,4-diphenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole- 2(3H)-one 0.38 3-(2-fluorophenyl)-5-(3-hydroxyphenoxy)-1,3,4-furadiazole-2(3H)-one 11.39 3-(2- Fluorophenyl)-5-(pyridin-3-yloxy)-1,3,4-furadiazole-2(3H)-one 38.39 3-(2,4-difluorophenyl)-5-(pyridine -3-yloxy)-1,3,4-furadiazole-2(3H)-one 48.57 3-(2-fluoro-4-(methylsulfonyl)phenyl)-5-(pyridine-3 -yloxy)-1,3,4-furadiazole-2(3H)-one 15.98 5-(2-bromoacridin-3-yloxy)-3-(4-methoxyphenyl)-1 , 3,4-furadiazole-2(3H)-one 3.36 5-(cyclohexyloxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2 (3 - Ketone 2.58 3-(3-Gas-2-fluorophenyl)-5-(cyclohexyloxy)-1,3,4-furadiazole-2(3H)-one 13.54 5-(cyclohexyloxy) -3-(4-decyloxyphenyl)-1,3,4-furadiazole-2(311)-one 45.11 5-(cyclohexyloxy) -3-(3-Fluoro-4',5'-dimethoxybiphenyl-4-yl)-1,3,4-furadiazole-2(3H)-one 30.3 3-(3-hydroxyl Phenyl)-5-phenoxy-1,3,4-furadiazole-2(3H)-one 14.04 5-(cyclohexyloxy)-3-(3-fluoro-3'-(trifluoromethyl) Oxy)biphenyl-4-yl)-1,3,4-furadiazole-2(3H)-one 35.39 115 200932732 5-(4-phenoxy)-3-(3-hydroxyphenyl) -1,3,4-furadiazole-2(3H)-one 1.21 5-(4-fluorophenoxy)-3-(3-hydroxyphenyl)-1,3,4-furadiazole- 2(3H)-ketone 2.95 3-(4-Gas-2-fluorophenyl)-5-phenylethoxy-1,3,4-furadiazole-2(3H)-one 10.49 3-(4- Hydroxyphenyl)-5-stupylethoxy-1,3,4-furadiazole-2(3H)-one 24.03 3-(2-fluorophenyl)-5-isobutoxy-1,3, 4-furadiazole-2(3H)-one 11.63 3-(4-hydroxyphenyl)-5-(3-phenylpropoxy)-1,3,4-furadiazole-2(3H)- Ketone 21.68 3-(4-Hydroxyphenyl)-5-(4-phenylbutoxy)-1,3,4-furadiazole-2(3H)-one 5.49 3-(4-hydroxyphenyl) -5-(5-phenylpentyloxy)-1,3,4-furadiazole-2(3H)-one 3.3 3-(4-hydroxyphenyl)-5-(6-phenylhexyloxy) -1,3,4-furadiazole-2(3H)-one 13.56 3-(4-Amino phenylphenyl)-5-(4-phenylphenyl)-1,3,4-σ 2 ° sitting -2 (3 Η)-ketone 5.16 3-(4-amine base 5-(4-methyllacylphenoxy)-1,3,4-oxadiazole-2(3Η)-one 8.32 3-(4-hydroxyphenyl)-5-(2-phenoxy Ethyloxy)-1,3,4-furadiazole-2(3Η)-one 33.2 5-(2-phenethylethoxy)-3-(4-hydroxyphenyl)-1,3,4 -furadiazole-2(3Η)-one 2.54 3-(4-Aminosulfonylphenyl)-5-(4-phenoxy)-1,3,4-furadiazole-2 (3Η )-ketone 5.89 3-(4-Amino-bromophenyl)-5-phenoxy-1,3,4-furadiazole-2(3Η)-one 7.61 3-phenyl-5-(5 -phenylpentyloxy)-1,3,4-furadiazole-2(3Η)-one 47.86 3-(2-fluorophenyl)-5-(4-phenylbutoxy)-1,3 , 4-furadiazole-2(3Η)-one 19.62 3-(4-Aminosulfonylphenyl)-5-(5-phenylpentyloxy)-1,3,4-furadiazole- 2(3Η)-ketone 0.09 3-(2-fluorophenyl)-5-(5-phenylpentyloxy)-1,3,4-furadiazole-2(3Η)-one 18.12 3-(2 ,4-difluorophenyl)-5-(5-phenylpentyloxy)-1,3,4-oxadiazole-2(3Η)-one 43.31 5-(4-(3,4-dimethyl Oxyphenyl)butoxy)-3-phenyl-1,3,4-furadiazole-2(3Η)-one 39.74 3-(2-Ga-5-fluorophenyl)-5-(5 -Phenylpentyloxy)-1,3,4-furadiazole-2(3Η)-one 9.94 5-(4-(3,4-dimethoxyphenyl)butoxy)-3-( 2-fluorophenyl)-1,3,4-furo-sigma sitting_2(3Η) -嗣3.85 5-(2-Phenylethoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2(3Η)-one 1.18 3-(2,4-di Fluorophenyl)-5-(4-(3+dimethoxyphenyl)butoxy)-1,3,4-furadiazole-2(311)-one 6.31 3-(4-gas-2 -fluorophenyl)-5-(4-(3,4-dimethoxyphenyl)butoxy)-1,3,4-furadiazole-2(3Η)-one 3.17 3-(3- Gas-2-fluorophenyl)-5-(4-(3,4-dimethoxyphenyl)butoxy)-1,3,4-furadiazole-2(311)-one 22.32 3- (4-Aminocarbonylphenyl)-5-phenoxy-1,3,4-furadiazole-2(3Η)-one 47.96 3-(4-Aminoyl-bromophenyl)-5-( 4-(3,4-dimethyllacylphenyl)butyl lactyl)_1,3,4-furadiazole-2(3Η)-one 0.09

116 200932732116 200932732

3-(2-氟苯基)-5-(4-(4-氟苯基)丁氧基)-1，3,4-呋二唑 -2(3H)-酮 12.7 3-(4-胺基羰基苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑 -2(3H)-酮 9.62 3-(4-胺基羰基苯基)-5-(4-甲氧基苯氧基)-1,3,4-呋二唑 -2(3H)-酮 18.41 3-(4-胺基羰基苯基)-5-(4-(4-氟苯基)丁氧基)-1，3,4-呋二唑-2(3H)-酮 1.01 3-(4-胺基羰基苯基)-5-(5-(4-氟苯基)戊基氧)-1,3,4-呋二唑-2(3H)-酮 0.07 3-(4-胺基羰基苯基)-5-(4-對-甲苯基丁氧基)-1,3,4-呋二唑-2(3H)-酮 0.06 3-(4-胺基羰基苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑 -2(3H)-酮 0.09 5-(聯苯基-4-基氧)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3H)-酮 0.97 5-(4-胺基羰基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑 -2(3H)-酮 14.5 5-(2-氟苯氧基)-3-(4-曱氧基苯基)-1,3,4-呋二嗤-2(3H)-酮 1.96 5-(3,4-二氟苯氧基)-3-(4-甲氧基苯基)-1,3,4-呋二唑 -2(3H)-酮 0.37 5-(2-氟苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3印-酮 1.1 5-(3,4-二氟苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑 -2(3H)-酮 0.46 3-(3-胺基苯基)-5-苯氡基-1,3,4-呋二唑-2(3H)-酮 52.35 3-(3-胺基苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑 -2(3H)-酮 0.87 5-(2-(聯苯基-4-基)乙乳基)-3-(4-¾基苯基)-1，3,4-咬二唑-2(3H)-酮 8.3 5-(2,4-二氟苯氧基)-3-(3,4-二甲氧基苯基)-1，3,4-呋二唑-2(3H)-酮 1.18 5-(4-氣苯氧基)-3-(3,4-二羥基苯基)-1,3,4-呋二唑 -2(3H)-酮 0.36 5-(2,4-二氟苯氧基)-3-(3,4-二羥基苯基)-1，3,4-呋二唑 -2(3H)-酮 0.1 5-(2,4-二氟苯氧基)-3-(3-甲氧基苯基)-1,3,4-呋二唑 -2(3H)-酮 0.92 5-(3,4-二甲氧基苯氧基)-3-(4-氟苯基)-1,3,4-呋二唑 -2(3H)-酮 13.95 5-(3,4-二羥基苯氧基)-3-(4-氟苯基)-1,3,4-呋二唑 -2(3H)-酮 57.19 3-(3-氟苯基)-5-(4-羥基苯氧基)-1,3,4-呋二唑-2(3H)-酮 46.83 5-(2,4-二氟苯氧基)-3-(3-羥基苯基)-1,3,4-呋二唑 -2(3H)-酮 0.22 5-(2-氣苯氧基)-3-(3-甲氧基苯基)-1,3,4-呋二唑-2(3H)-酮 16.18 3-(4-氣-2-氟苯基)-5-(4-羥基苯氧基)-1,3,4-呋二唑 -2(3H)-酮 8.06 3-(4-氟苯基)-5-(4-羥基苯氧基)-1，3,4-呋二唑-2(3H)-酮 40.67 117 200932732 5-(3,5-二氟苯乙氧基)-3-(4-羥基苯基)-1，3,4-呋二唑 -2(3Η)-酮 3.9 5-(2-氣苯氧基)-3-(3-羥基苯基)-1,3,4-呋二唑-2(3印-酮 9.36 5-(4-氣苯氧基)-3-(2'-羥基聯苯基-4-基)-1,3,4-呋二唑 -2(3Η)-酮 2.77 3-(3-氣-2-氟苯基)-5-(4-羥基苯氧基)-1,3,4-呋二唑 -2(3Η)-酮 22.72 5-(4-氣苯氧基)-3-(2'-甲氧基聯苯基-4-基)-1,3,4-呋二唑-2(3Η)-酮 0.55 5-(3,4-二羥基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑 -2(3Η)-酮 36.2 5-(4-氣苯氧基)-3-(3-氟-4-羥基苯基)-1,3,4-呋二唑 -2(3Η)-酮 1.05 5-(2,4-二氟苯氧基)-3-(2'-甲氧基聯苯基-4-基)-1,3,4-呋二唑-2(3Η)-酮 1.86 5-(4-氣苯氧基)-3-(2-氟-4-羥基苯基)-1,3,4-呋二唑 -2(3Η)-酮 0.01 5-(4-氣苯氧基)-3-(2’-羥基聯苯基-3-基)-1,3,4-呋二唑 -2(3Η)-酮 6.02 5-(2,4-二氟苯氧基)-3-(4-羥基-3-甲基苯基)-1，3,4-吱二唑-2(3Η)-酮 0.09 5-(4-氣苯氧基)-3-(4-羥基-3-甲基苯基)-1,3,4-呋二唑 -2(3Η)-酮 0.31 5-(2,4-二氟苯氧基)-3-(2’-羥基聯苯基-4-基)-1,3,4-呋二 β坐-2(3Η)-嗣 1.48 5-(4-氣笨氧基)-3-(2'-甲氧基聯苯基-3-基)-1，3,4-呋二唑-2(3Η)-酮 4.91 5-(2,4-二氟苯氧基)-3-(4-羧基-3,5-二曱基苯基)-1,3,4-呋二唑-2(311)-酮 0.18 5-(4-氣笨氧基)-3-(4-羥基-3,5-二曱基苯基)-1,3,4-呋二唑-2(3Η)-酮 0.51 5-(2,4-二氟苯氧基)-3-(4-(4-曱氧基苄氧基)苯基)-1,3,4-呋二唑-2(3Η)-酮 0.48 5-(2,4-二氟苯氧基)-3-(4-(3-曱氧基苄氧基)苯基)-1,3,4-呋二唑-2(3Η)-酮 0.2 5-(4-氣苯氧基)-3-(3,5-二羥基苯基)-1,3,4-呋二唑 -2(3Η)-酮 2.42 5-(2,4-二氟苯氧基)-3-(4-(2-甲氧基苄氧基)苯基)-1,3,4-呋二唑-2(3Η)-酮 0.27 3-(4-苯甲醯基氧苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑 -2(3Η)-酮 8.13 3-(4-乙醯氧基苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑 -2(3Η)-酮 0.38 3-(4-苯甲醯基氧苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑-2(3Η)-酮 0.79 3-(4-異丁醯基氧苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑-2(3Η)-酮 0.26 5-(2,4-二氟苯氧基)-3-(3-甲氧基-4-硝基苯基)-1，3,4-呋二唑-2(3Η)-酮 52.39 11Β3-(2-fluorophenyl)-5-(4-(4-fluorophenyl)butoxy)-1,3,4-furadiazole-2(3H)-one 12.7 3-(4-amine Phenylcarbonyl)phenyl-5-(4-phenoxy)-1,3,4-furadiazole-2(3H)-one 9.62 3-(4-aminocarbonylphenyl)-5-(4 -Methoxyphenoxy)-1,3,4-furadiazole-2(3H)-one 18.41 3-(4-Aminocarbonylphenyl)-5-(4-(4-fluorophenyl) Butoxy)-1,3,4-furadiazole-2(3H)-one 1.01 3-(4-Aminocarbonylphenyl)-5-(5-(4-fluorophenyl)pentyloxy) -1,3,4-furadiazole-2(3H)-one 0.07 3-(4-aminocarbonylphenyl)-5-(4-p-tolylbutoxy)-1,3,4- Furadiazole-2(3H)-one 0.06 3-(4-Aminocarbonylphenyl)-5-(5-phenylpentyloxy)-1,3,4-furadiazole-2(3H)- Ketone 0.09 5-(biphenyl-4-yloxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 0.97 5-(4-aminocarbonyl) Phenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 14.5 5-(2-fluorophenoxy)-3-(4-oxime Phenyl)-1,3,4-furodiindole-2(3H)-one 1.96 5-(3,4-difluorophenoxy)-3-(4-methoxyphenyl)-1, 3,4-furadiazole-2(3H)-one 0.37 5-(2-fluorophenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2 (3 impressions) -ketone 1.1 5-(3,4-difluorophenoxy)-3-(4-hydroxyphenyl)- 1,3,4-furadiazole-2(3H)-one 0.46 3-(3-aminophenyl)-5-phenylindol-1,3,4-furadiazole-2(3H)-one 52.35 3-(3-Aminophenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2(3H)-one 0.87 5-(2-(linked Phenyl-4-yl)ethyl lactyl)-3-(4-3⁄4-ylphenyl)-1,3,4-oxadiazole-2(3H)-one 8.3 5-(2,4-difluorobenzene Oxy)-3-(3,4-dimethoxyphenyl)-1,3,4-furadiazole-2(3H)-one 1.18 5-(4-phenoxy)-3-( 3,4-dihydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 0.36 5-(2,4-difluorophenoxy)-3-(3,4-dihydroxyl Phenyl)-1,3,4-furadiazole-2(3H)-one 0.1 5-(2,4-difluorophenoxy)-3-(3-methoxyphenyl)-1,3 , 4-furadiazole-2(3H)-one 0.92 5-(3,4-dimethoxyphenoxy)-3-(4-fluorophenyl)-1,3,4-furadiazole- 2(3H)-ketone 13.95 5-(3,4-Dihydroxyphenoxy)-3-(4-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 57.19 3- (3-fluorophenyl)-5-(4-hydroxyphenoxy)-1,3,4-furadiazole-2(3H)-one 46.83 5-(2,4-difluorophenoxy)- 3-(3-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 0.22 5-(2-phenoxy)-3-(3-methoxyphenyl)- 1,3,4-furadiazole-2(3H)-one 16.18 3-(4-Gas-2-fluorophenyl)-5-(4-hydroxyphenoxy -1,3,4-furadiazole-2(3H)-one 8.06 3-(4-fluorophenyl)-5-(4-hydroxyphenoxy)-1,3,4-furadiazole -2(3H)-ketone 40.67 117 200932732 5-(3,5-Difluorophenylethoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(3Η)- Ketone 3.9 5-(2-Vinylphenoxy)-3-(3-hydroxyphenyl)-1,3,4-furadiazole-2 (3-acetone 9.36 5-(4-phenoxy) -3-(2'-hydroxybiphenyl-4-yl)-1,3,4-furadiazole-2(3Η)-one 2.77 3-(3-Gas-2-fluorophenyl)-5- (4-hydroxyphenoxy)-1,3,4-furadiazole-2(3Η)-one 22.72 5-(4-Vephenoxy)-3-(2'-methoxybiphenyl- 4-yl)-1,3,4-furadiazole-2(3Η)-one 0.55 5-(3,4-dihydroxyphenoxy)-3-(2-fluorophenyl)-1,3, 4-furadiazole-2(3Η)-one 36.2 5-(4-Vinylphenoxy)-3-(3-fluoro-4-hydroxyphenyl)-1,3,4-furadiazole-2 ( 3Η)-ketone 1.05 5-(2,4-difluorophenoxy)-3-(2'-methoxybiphenyl-4-yl)-1,3,4-furadiazole-2 (3Η )-ketone 1.86 5-(4-Vephenoxy)-3-(2-fluoro-4-hydroxyphenyl)-1,3,4-furadiazole-2(3Η)-one 0.01 5-(4 - gas phenoxy)-3-(2'-hydroxybiphenyl-3-yl)-1,3,4-furadiazole-2(3Η)-one 6.02 5-(2,4-difluorobenzene Oxy)-3-(4-hydroxy-3-methylphenyl)-1,3,4-oxadiazole- 2(3Η)-ketone 0.09 5-(4-Vephenoxy)-3-(4-hydroxy-3-methylphenyl)-1,3,4-furadiazole-2(3Η)-one 0.31 5-(2,4-Difluorophenoxy)-3-(2'-hydroxybiphenyl-4-yl)-1,3,4-furodi-β-spin-2(3Η)-嗣1.48 5- (4-gasooxy)-3-(2'-methoxybiphenyl-3-yl)-1,3,4-furadiazole-2(3Η)-one 4.91 5-(2,4 -difluorophenoxy)-3-(4-carboxy-3,5-diamidinophenyl)-1,3,4-furadiazole-2(311)-one 0.18 5-(4-gas Oxy)-3-(4-hydroxy-3,5-diamidinophenyl)-1,3,4-furadiazole-2(3Η)-one 0.51 5-(2,4-difluorophenoxy 3-(4-(4-decyloxybenzyloxy)phenyl)-1,3,4-furadiazole-2(3Η)-one 0.48 5-(2,4-difluorophenoxy 3-(4-(3-decyloxybenzyloxy)phenyl)-1,3,4-furadiazole-2(3Η)-one 0.2 5-(4-phenoxy)- 3-(3,5-dihydroxyphenyl)-1,3,4-furadiazole-2(3Η)-one 2.42 5-(2,4-difluorophenoxy)-3-(4-( 2-methoxybenzyloxy)phenyl)-1,3,4-furadiazole-2(3Η)-one 0.27 3-(4-benzylideneoxyphenyl)-5-(4-gas Phenoxy)-1,3,4-furadiazole-2(3Η)-one 8.13 3-(4-acetoxyphenyl)-5-(2,4-difluorophenoxy)-1 , 3,4-furadiazole-2(3Η)-one 0.38 3-(4-benzhydryloxyphenyl)- 5-(2,4-difluorophenoxy)-1,3,4-furadiazole-2(3Η)-one 0.79 3-(4-isobutyldecyloxyphenyl)-5-(2,4- Difluorophenoxy)-1,3,4-furadiazole-2(3Η)-one 0.26 5-(2,4-difluorophenoxy)-3-(3-methoxy-4-nitro Phenyl)-1,3,4-furadiazole-2(3Η)-one 52.39 11Β

〇 200932732 5-(2,4-二氟苯氧基)-3-(3-羥基-4-硝基苯基)-1，3,4-呋二 4-2i3HV 酮 51.6 5-(4-氯苯氧基)-3-(3-經基-4-石肖基苯基)-1，3,4-咬二°坐 -2i3HV 酮 _ _ 56.4 5-(2,4-二氣苯氧基)-3-(7-羥基萘-2-基)-1，3,4-吱二唑 -2GHV 酮 3-(4-胺基-3-經基苯基)-5-(2,4-二氟苯乳基)-1，3,4-吱二岫-2GH)-酮 __ 3-(4-胺基-3-甲氧基苯基)-5-(2,4-二氟苯氧基)-1，3,4-咬 -唑-2GH)-酮鹽酸鹽 3-(4-胺基-3-(2-曱氧基乙氧基)苯基)-5-(2,4-二氟苯氧其卩1.3.4-呔二唑-2(3印-嗣 _ 3-(4-胺基苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二嗤 -2(3H)-酮〇.〇4 3-(4-(1Η-° 比洛-I-基)苯基)-5-(2,4-二氣苯乳基)-1，3,4_咬二唑-2(3H)-酮 7.4 3-(4-胺基苯基)-5-(4-氣苯氧基)-1，3,4-呋二唑-2(3H)-酮 0.51 3-(4-(1Η-β比咯-1-基)苯基)-5-(4-氣苯氧基)-1,3,4-吱二 9.33 唑-2(3Η)-酮 3-(3-胺基-4-甲氧基苯基)-5-(對-甲苯基氧)-1,3,4-呋二唑-2(3Η)-酮 3-(3-胺基-4-甲氧基苯基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑-2(3Η)-酮 5-(2,4-二氟笨氧基)-3-(4-甲氧基-3-(1Η-«比咯-1-基)苯基)-1,3,4-呋二唑-2(311)-酮 3-(5-胺基-2-氟-4-曱氧基苯基)-5-(2,4-二氟苯氧 37.03 1.9 0.35 0.35 〇.〇4 0.31 基)-1,3,4-呋二唑-2(3Η)-酮鹽酸鹽 5-(2,4-二氟苯氧基)-3-(2-氟-4-羥基苯基)-1，3,4-呋二唑 -2(3Η)-酮 3-(4-胺基-3-甲氧基苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二。坐·2(3Η)-嗣 Ο 依據下列方法，在投予本發明的化合物之動物組、織中，測定活體内的FAAH抑制性活性。動物之處理實驗中所用的動物係自Interfauna Ulrica公司（西班牙）所取得之雄性NMRI小鼠（體重27-44克）。在受控的環户 (12小時光/暗週期及室溫為22±1。〇下，每籠飼養5隹' 飼料與自來水均自由取用，及實驗皆在白天期間鼠。使用動物餵食用彎曲型不鏽鋼注射針（美國丁。 (Perfectum)公司），經由口服途徑，對於動費克垣 119 铋予30毫克/ 200932732 公斤的ΒΙΑ化合物（8毫升/公斤；化合物懸浮於〇5%羧基甲基纖雉素(CMC)或溶於水），或投予8毫升/公斤的〇 5%CMC (對照組）。在犧牲前15分鐘’藉由以腹膜内方式投予6〇毫克 /公斤的戊巴比妥(pentobarbital)，將動物麻醉。移除一部份 5 的肝、左肺葉及不包括小腦之腦部，及置入含有膜緩衝液 (3mM氣化鎂、ImMEDTA、酸驗值為7.4的50mM Tris HC1) 的塑膠瓶中。在分析之前，將組織儲存於_3〇。匚。在化合物投藥作用之前，讓動物禁食過夜，除非該期間超過18小時；在投藥當天的早晨將飼料移除，及在同一 φ 10 天下午投予化合物。然後只供給動物水。所有動物處理程序均嚴格遵守歐洲實驗用與其他科學 - 用途的脊椎動物之保護法令（86/609CEE)及葡萄牙法律 ‘ (Decreto-Lei 129/92、Portarias l〇〇5/92e 1131/97)。所用的動物數目，係與目前立法及科學正直品性相符之可能最少量。 15 試劑輿溶液極樂醯胺（anandamide)[乙醇胺_ 1 _3H_K40-60Ci/毫莫耳）係自美國放射線化學樂品（American Radiochemicals)公司 ❹ 取得。其他所有試劑係自西克瑪艾爾迪希（Sigma_Aldrich) 公司取得。〇ptiphase Supermix係自柏金愛默(Perkin Elmer) 20 公司取得，而活性碳係自西克瑪艾爾迪希（Sigma-Aldrich) 公司取得。組織製備作闲組織在冰上解凍，及置於10倍體積的膜緩衝液(3 mM 氣化鎂、1 mM EDTA、酸驗值為7·4的50 mM Tris HC1)中， 120 200932732 以波特愛維瀚(PotterElvejhem)均化器（腦：於5〇〇rpm打擊8 次）或海朵夫迪愛斯(Heidolph Diax)均化器（肝：在第5級20 秒打擊2次及暫停30秒），進行均化作用。 5 ❹ 10 15 ❹ 20 使用BSA(50-250微克/毫升）的一標準曲線，以BioRad 蛋白質分析(BioRad)測定組織中的總蛋白質。酵素分析反應混合物(總體積為200微升)含有：2 μΜ ΑΕΑ(2 μΜ ΑΕΑ + 5 ηΜ 3Η-ΑΕΑ) ; 0.1 % 無脂肪酸的BSA ;位於lmM EDTA中的15微克(腦）、5微克(肝）或50微克(肺)蛋白質；酸鹼質為7.6的lOmMTris。在37°C預培養15分鐘之後，藉由添加受質溶液（冷的AEA+經放射線標記的AEA + BSA)而起始反應。反應進行10分鐘（腦與肝）或7分鐘（肺），然後藉由添加400微升活性碳懸浮液（位於32毫升的〇 5M鹽酸中之8克的炭及處於連續攪拌狀態），而終止反應。在攪拌作用下，在室溫中培養30分鐘之後，藉由在微量離心機中的離心作用（於13000 rpm離心10分鐘），將炭沈澱。在先行置入槽式平ja中的800微升〇ptiphaseSupermix閃爍液中添加細微升的上清液。在Microbeta TriLux閃爍計數器中，測〜每分鐘計數值(cpm)。在各分析中，皆製備空白組(不具有蛋白質卜在減去空白組之後，計算剩餘酵素活性相對於對照組 (無化合物）之百分比。 ’'…' 結果示於第4表： 121 200932732 第4表化合物 FAAHi 活性(％對照組小鼠肝 (30mgkglh)) FAAHi活性 (%對照組小鼠腦（30mg kg lh)) 3-(3’-甲氧基聯苯基-4-基)-5-苯氧基 -1，3,4-呋二唑-2(3H)-酮 67.58 93.2 5-(节氧基)-3-(2-氟苯基)-1，3,4-呋二唑-2(3H)-酮 31.12 103.63 3-(3-靖基苯基)-5-苯乳基-1，3,4-咬二唑-2(3H)-酮 73.47 87.28 3-(4-羥基苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 46.3 97.32 5-(苄氧基)-3-(3-溪苯基)-1,3,4-吱二唑-2(3Η)-酮 70.43 96.92 5-(苄氧基)-3-(聯苯基-3-基)-1，3,4-呋二唑-2(3Η)-酮 71.36 71.23 5-(4-氯苯氧基)-3-(2-氟苯基)-1，3,4_ 吱二嗤-2(3Ϊί)-調 45.9 76.22 3-(2-氟苯基)-5-苯氧基-1,3,4 -呋二唑 -2(3Η)-酮 72.15 97 3-(2-氟苯基)-5-(4-甲氧基苯氧基)-1，3,4-呋二唑-2C3H)-酮 72.04 68.77 5-(苄氧基)-3-(2,4-二氟苯基)-1，3,4-吱二0i-2(3H)-_ 69.86 79.94 5-(4-氣苯氧基)-3-(2,5-二氟苯基)-1，3,4-呋二唑-2(3H)-酮 70.5 77.59 3-(2,4-二氟苯基)-5-苯氧基-1,3,4-呋二唑-2(3H)-酮 65.24 86.48 3-(2,4-二氟苯基)-5-(秦-1-基氧)-1，3,4-呋二唑-2(3H)-酮 78.72 94.69 5-(2-氣苯氧基)-3-(2-氟苯基)-1，3,4-呋二唑-2(3H)-酮 67.76 106.7 5-(2,4-二乳苯氧基)-3-苯基· 1，3,4-咬二 σ坐-2(3H)-明 39.07 93.97 5-(2,4-二氟苯氧基)-3-(4-曱氧基苯基)-1,3,4-呋二唑-2(3H)-酮 52.81 94.15 3-(4-氣-2-氟苯基)-5-(4-甲氧基苯氧基)-1，3,4-呋二唑-2PH)-酮 75.9 90.87 5-(4-氣苯氧基)-3-(4-曱氧基苯基)-1,3,4-呋二唑-2(3H)-酮 75.22 92.94 5-(4-氣苯氧基)-3-(4-羥基苯基)-1，3,4-呋二唑-2(3H)-酮 19.56 37.69 5-(3,5-二曱氧基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2PH)-酮 76.19 87.43 5-(4-氰基苯氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(311)-酮 74.33 85.02〇200932732 5-(2,4-Difluorophenoxy)-3-(3-hydroxy-4-nitrophenyl)-1,3,4-furodi 4-2i3HV ketone 51.6 5-(4-chloro Phenoxy)-3-(3-transyl-4-stone-cholylphenyl)-1,3,4-bito-2°3i3HV ketone _ _ 56.4 5-(2,4-diphenoxy)- 3-(7-hydroxynaphthalen-2-yl)-1,3,4-oxadiazole-2GHV keto 3-(4-amino-3-phenylphenyl)-5-(2,4-difluoro Benzyl lactyl-1,3,4-indenyl-2GH)-keto__ 3-(4-amino-3-methoxyphenyl)-5-(2,4-difluorophenoxy )-1,3,4-Bite-azole-2GH)-ketohydrochloride 3-(4-amino-3-(2-decyloxyethoxy)phenyl)-5-(2,4- Difluorophenoxy oxime 1.3.4-oxadiazole-2 (3-indole-3-(4-aminophenyl)-5-(2,4-difluorophenoxy)-1,3, 4-furodiindole-2(3H)-ketooxime.〇4 3-(4-(1Η-°Bilo-I-yl)phenyl)-5-(2,4-diphenylphenyl)- 1,3,4_ oxadiazole-2(3H)-one 7.4 3-(4-aminophenyl)-5-(4-phenoxy)-1,3,4-furadiazole-2 (3H)-ketone 0.51 3-(4-(1Η-βpyrrol-1-yl)phenyl)-5-(4-phenoxy)-1,3,4-indenyl 9.33 azole-2 ( 3-Η)-keto 3-(3-amino-4-methoxyphenyl)-5-(p-tolyloxy)-1,3,4-furadiazole-2(3Η)-one 3-( 3-amino-4-methoxyphenyl)-5-(2,4-difluoro Oxy)-1,3,4-furadiazole-2(3Η)-one 5-(2,4-difluoroindolyl)-3-(4-methoxy-3-(1Η-« ratio [rho-1-yl)phenyl)-1,3,4-furadiazole-2(311)-one 3-(5-amino-2-fluoro-4-indolylphenyl)-5- 2,4-difluorophenoxy 30.7.03 1.9 0.35 0.35 〇.〇4 0.31 base)-1,3,4-furadiazole-2(3Η)-one hydrochloride 5-(2,4-difluorophenoxy 3-(2-fluoro-4-hydroxyphenyl)-1,3,4-furadiazole-2(3Η)-one 3-(4-amino-3-methoxyphenyl)- 5-(2,4-difluorophenoxy)-1,3,4-furodi. Sodium 2(3Η)-嗣Ο According to the following method, in the animal group and woven fabric to which the compound of the present invention is administered, The FAAH inhibitory activity in vivo was measured. The animals used in the animal treatment experiments were male NMRI mice (body weight 27-44 g) obtained from Interfauna Ulrica (Spain). In a controlled household (12 hours light/dark cycle and room temperature of 22 ± 1. under the armpit, 5 每 per cage) feed and tap water are free to use, and the experiment is carried out during the day. Curved stainless steel injection needle (Perfectum), via oral route, for the treatment of 费垣垣垣 30 30 30 mg / 200932732 kg of bismuth compound (8 ml / kg; compound suspended in 〇 5% carboxymethyl Fibrin (CMC) or dissolved in water), or 5% CMC (control) administered at 8 ml/kg. 15 minutes before sacrifice 'by intraperitoneal administration of 6 mg/kg pentane Pentobarbital, anesthetize the animal. Remove a portion of the 5 liver, left lobe, and brain that does not include the cerebellum, and place the membrane buffer (3 mM magnesium oxide, ImMEDTA, acid test value 7.4). In a 50 mM Tris HC1) plastic bottle, store the tissue at _3 〇 before analysis. 让 Allow the animal to fast overnight before the compound is administered, unless the period exceeds 18 hours; feed on the morning of the day of administration Remove and apply compound on the same φ 10th afternoon Then only animal water is supplied. All animal handling procedures are in strict compliance with the European Law and Other Science-Use Vertebrate Protection Act (86/609 CEE) and Portuguese Law' (Decreto-Lei 129/92, Portarias l〇〇5 /92e 1131/97). The number of animals used is the least likely to be in line with current legislation and scientific integrity. 15 Reagent 舆 solution anandamide [ethanolamine _ 1 _3H_K40-60Ci / millimolar) Obtained from American Radiochemicals. All other reagents were obtained from Sigma_Aldrich. 〇ptiphase Supermix was obtained from Perkin Elmer 20 and activated carbon was obtained from Sigma-Aldrich. The tissue-prepared tissue was thawed on ice and placed in 10 volumes of membrane buffer (3 mM magnesium carbonate, 1 mM EDTA, 50 mM Tris HC1 with an acid value of 7.4), 120 200932732 Potter Elvejhem homogenizer (brain: 8 hits at 5 rpm) or Heidolph Diax homogenizer (liver: 2 hits and pauses at level 5 for 20 seconds) 30 seconds), homogenization. 5 ❹ 10 15 ❹ 20 Total protein in tissues was determined by BioRad Protein Assay (BioRad) using a standard curve of BSA (50-250 μg/ml). The enzyme assay reaction mixture (total volume of 200 μl) contains: 2 μΜ ΑΕΑ (2 μΜ ΑΕΑ + 5 ηΜ 3Η-ΑΕΑ); 0.1% fatty acid-free BSA; 15 μg (brain), 5 μg in lmM EDTA ( Liver) or 50 micrograms (lung) protein; 10 mM Tris with a pH of 7.6. After pre-incubation for 15 minutes at 37 ° C, the reaction was initiated by the addition of a substrate solution (cold AEA + radiolabeled AEA + BSA). The reaction was carried out for 10 minutes (brain and liver) or 7 minutes (lung) and then terminated by the addition of 400 microliters of activated carbon suspension (8 grams of charcoal in 32 ml of 5M hydrochloric acid and in continuous stirring). reaction. After incubating for 30 minutes at room temperature with stirring, the carbon was precipitated by centrifugation in a microcentrifuge (centrifugation at 13,000 rpm for 10 minutes). A fine liter of supernatant was added to an 800 microliter 〇ptiphaseSupermix scintillation fluid placed in a trough ja. In the Microbeta TriLux scintillation counter, measure the count value per minute (cpm). In each analysis, a blank group was prepared (no protein was added. After subtracting the blank group, the percentage of remaining enzyme activity relative to the control group (no compound) was calculated. ''...' The results are shown in Table 4: 121 200932732 4 Table compound FAAHi activity (% control mouse liver (30 mg kglh)) FAAHi activity (% control mouse brain (30 mg kg lh)) 3-(3'-methoxybiphenyl-4-yl)-5 -phenoxy-1,3,4-furadiazole-2(3H)-one 67.58 93.2 5-(hydroxy)-3-(2-fluorophenyl)-1,3,4-furadiazole -2(3H)-ketone 31.12 103.63 3-(3-jingylphenyl)-5-phenyllacyl-1,3,4-oxadiazole-2(3H)-one 73.47 87.28 3-(4-hydroxybenzene 5-(phenoxy-1,3,4-furadiazole-2(3H)-one 46.3 97.32 5-(benzyloxy)-3-(3-xylphenyl)-1,3,4 -oxadiazole-2(3Η)-ketone 70.43 96.92 5-(Benzyloxy)-3-(biphenyl-3-yl)-1,3,4-furadiazole-2(3Η)-one 71.36 71.23 5-(4-Chlorophenoxy)-3-(2-fluorophenyl)-1,3,4_吱二嗤-2(3Ϊί)-调45.9 76.22 3-(2-Fluorophenyl)-5 -phenoxy-1,3,4-furadiazole-2(3Η)-one 72.15 97 3-(2-fluorophenyl)-5-(4-methoxyphenoxy)-1,3, 4-furadiazole-2C3H)-ketone 72.04 68.77 5-(Benzyloxy)-3-(2,4-difluorophenyl)-1,3,4-indenyl 2i-2(3H)-- 69.86 79.94 5-(4-Vephenoxy)- 3-(2,5-Difluorophenyl)-1,3,4-furadiazole-2(3H)-one 70.5 77.59 3-(2,4-difluorophenyl)-5-phenoxy- 1,3,4-furadiazole-2(3H)-one 65.24 86.48 3-(2,4-difluorophenyl)-5-(qin-1-yloxy)-1,3,4-furo Azole-2(3H)-one 78.72 94.69 5-(2-Vinylphenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 67.76 106.7 5 -(2,4-dilacphenoxy)-3-phenyl· 1,3,4-bito-sigma-spin-2(3H)-ming 39.07 93.97 5-(2,4-difluorophenoxy) -3-(4-decyloxyphenyl)-1,3,4-furadiazole-2(3H)-one 52.81 94.15 3-(4-Gas-2-fluorophenyl)-5-(4- Methoxyphenoxy)-1,3,4-furadiazole-2PH)-one 75.9 90.87 5-(4-Vephenoxy)-3-(4-decyloxyphenyl)-1,3 , 4-furadiazole-2(3H)-one 75.22 92.94 5-(4-Vephenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2 (3H) -ketone 19.56 37.69 5-(3,5-Dimethoxyphenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2PH)-one 76.19 87.43 5-(4 -Cyanophenoxy)-3-(2-fluorophenyl)-1,3,4-furadiazole-2(311)-one 74.33 85.02

122 200932732 5-(4-氟苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3印-酮 30.89 81.63 5-(2,4-二氟苯氧基)-3-(4-羥基苯基)- 1,3,4-呋二唑-2(311)-酮 11.94 85.59 5-(聯苯基-4-基氧)-3-(2-氟苯基)_ 1，3,4-呋二唑-2(3H)-酮 60.42 99.51 3-(4-羥基苯基)-5-(3-(三氟曱基)苯氧基)-1,3,4-呋二唑-2(3H)-酮 69.9 95.5 5-(3,5-二羥基苯氧基)-3-(2-氟苯基)-1，3,4-呋二唑-2(3H)-酮 39.57 72.49 3-(4-¾基苯基)-5-(4-梢基苯乳基)-1，3,4-呋二唑-2(3H)-酮 45 96.3 5-(2,4-二氣苯氧基)-3-(4-羥基苯基)- 1，3,4-呋二唑-2(311)-酮 9.17 59.18 5-(環己氧基)-3-(2-氟苯基)-1,3,4-呋二唑-2(3H)-酮 56.98 77.59 3-(3-¾基苯基)-5-苯乳基-1，3,4-咬二 33.01 94.66 5-(4-氣苯氧基)-3-(3-羥基苯基)-1,3,4-呋二唑-2(3田-酮 10.26 100.2 5-(4-氟苯氧基)-3-(3-羥基苯基)-1，3,4-呋二唑-2(3H)-酮 24.27 99.06 3-(2-氟苯基)-5-異丁氧基-1,3,4-呋二嗤-2(311)-嗣 26.55 83.52 3-(4-經基苯基)-5-(3-苯基丙氧基)_ 1，3,4-呋二唑-2(311)-酮 38.45 85.58 3-(4-羥基苯基)-5-(4-苯基丁氧基)-1，3,4-呋二唑-2(311)-酮 65.84 95.66 3-(4-羥基苯基)-5-(6-苯基己基氧)-1，3,4-呋二唑-2(3H)-酮 51.19 96.15 5-(2-氣苯乙氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(3印-酮 31.37 92.16 3-(4-胺基磺醯基苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑-2(3H)-酮 45.73 74.76 3-(4-胺基羰基苯基)-5-(4-(4-氟苯基）丁氧基)-1,3,4-呋二唑-2(3H)-酮 59.61 106.79 3-(4-胺基叛基苯基)-5-(5-(4-氣苯基）戊基氧)-1，3,4-呋二唑-2(3H)-酮 71.77 105.07 3-(4-胺基羰基苯基)-5-(4-對-甲苯基丁氧基H，3,4-呋二唑-2(3H)-酮 30.46 68.63 3-(4-胺基羰基苯基)-5-(5-苯基戊基氧)-1,3,4-呋二唑-2(3H)-酮 56.07 84.41 5-(聯苯基-4-基氧)-3-(4-經基苯基)_ 1，3,4-呋二唑-2(311)-酮 17.29 62.46 5-(2-复苯氧基)-3-(4-曱氧基苯基)-1,3,4-呋二唑-2(311)-酮 44.98 88.26 5-(3,4-二氟苯氧基)-3-(4-甲氧基苯基)-1，3,4-呋二唑-2(3H)-酮 49.6 85.72 123 200932732 5-(2-氟苯氧基)-3-(4-羥基苯基)-1，3,4-呋二唑-2(311)-酮 44.44 93.98 5-(3,4-二氟苯氧基)-3-(4-羥基苯基)-1,3,4-呋二唑-2(311)-酮 17.28 58.22 3-(3-胺基笨基)-5-(2,4-二氟苯氧基)-1，3,4-呋二唑-2(3H)-酮 21.63 82.92 5-(4-氣苯氧基)-3-(3,4-二羥基苯基)-1,3,4-呋二唑-2(311)-酮 4.94 83.36 5-(2,4-二氟苯氧基)-3-(3,4-二羥基苯基)-1,3,4-呋二唑-2(3H)-酮 3.56 65.78 5-(2,4-二氟苯氧基)-3-(3-羥基苯基)- 1，3,4-呋二唑-2(311)-酮 11.85 93.77 5-(4-氣苯乳基)-3-(3-氟-4-經基苯基)_ 1,3,4-呋二唑-2(3H)-酮 49.56 86.55 5-(4-氯苯乳基)-3-(2-氣-4-¾基苯基)_ 1，3,4-呋二唑-2(3H)-酮 3.8 64.34 5-(2,4-二氟苯氧基)-3-(4-羥基-3-甲基笨基)-1,3,4-呋二唑-2(3印-酮 10.23 48.25 5-(4-氣苯氧基)-3-(4-羥基-3-甲基苯基)-1,3,4-呋二唑-2(3H)-酮 37.45 50.01 5-(2,4-二氟苯氧基)-3-(4-羥基-3,5-二甲基苯基)-1,3,4-呋二唑-2(311)-酮 7.58 67.44 5-(2,4-二氟苯氧基)-3-(4-(3-甲氧基苄氧基)笨基)-1,3,4-呋二唑-2(311)-酮 45.86 96.03 3-(4-苯甲醯基氧苯基)-5-(4-氣苯氧基)-1,3,4-呋二唑-2(3H)-酮 108.8 94.4 3-(4-乙醯氧基苯基)-5-(2,4-二氟苯氧基)-1,3,4-呋二唑-2(3H)-酮 73.67 96.55 3-(4-異丁醯基氧苯基)-5- (2,4-二氟苯氧基)-1,3,4-呋二唑-2(3H)-酮 55.9 90.41 5-(2,4-二氟苯氧基)-3-(7-經基秦-2-基)-1，3,4-呋二唑-2(3H)-酮 79.41 86.37 3-(4-胺基-3-甲乳基苯基)-5-(2,4-二氣笨氧基)-1，3,4-呋二唑-2(3H)-酮鹽酸鹽 4.19 9.61 3-(4-胺基-3-(2-甲氧基乙氧基)苯基） -5-(2,4-二氟苯氧基)-1,3,4-呋二唑 -2(3H)-酮 4.99 6.76 如自上述試驗中明顯可見，皆以具有一個5-0-取代 3-N-苯基-1,3,4-呋二唑酮結構單元為特徵之本發明的化合物，其具有意外高的FAAH抑制作用水平，使得該等新穎化合物成為用於治療或預防FAAH相關醫學病況之具潛力的 5 候選藥物。而且，該意外高的FAAH抑制作用不僅在試管 200932732 中，亦在活體内明顯可見。而且，有關活體内數據之比較亦顯示，具有一個5 〇_ 取代3-N-苯基-1，3，4-»夫二β坐酮結構單元的化合物之FAAH抑制性活性，其特徵在於相較於在中樞神經系統(CNS)的活 5 性’其對於週圍神經具有一選擇性。關於廣範圍的高活性化合物之上述數據顯示，具下列結構式（III)之5-0-取代3-N-苯基-1，3,4-吱二唾酮結構單元： 0122 200932732 5-(4-Fluorophenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2 (3 - ketone 30.89 81.63 5-(2,4-difluoro Phenoxy)-3-(4-hydroxyphenyl)- 1,3,4-furadiazole-2(311)-one 11.94 85.59 5-(biphenyl-4-yloxy)-3-(2 -fluorophenyl)_ 1,3,4-furadiazole-2(3H)-one 60.42 99.51 3-(4-hydroxyphenyl)-5-(3-(trifluoromethyl)phenoxy)- 1,3,4-furadiazole-2(3H)-one 69.9 95.5 5-(3,5-dihydroxyphenoxy)-3-(2-fluorophenyl)-1,3,4-furo Oxazole-2(3H)-one 39.57 72.49 3-(4-3⁄4ylphenyl)-5-(4-primylphenyl lactyl)-1,3,4-furadiazole-2(3H)-one 45 96.3 5-(2,4-Diphenoxy)-3-(4-hydroxyphenyl)- 1,3,4-furadiazole-2(311)-one 9.17 59.18 5-(cyclohexyloxy) )-3-(2-fluorophenyl)-1,3,4-furadiazole-2(3H)-one 56.98 77.59 3-(3-3⁄4ylphenyl)-5-phenyllacyl-1,3 , 4-biting two 33.01 94.66 5-(4-phenoxy)-3-(3-hydroxyphenyl)-1,3,4-furadiazole-2 (3 field-ketone 10.26 100.2 5-(4 -fluorophenoxy)-3-(3-hydroxyphenyl)-1,3,4-furadiazole-2(3H)-one 24.27 99.06 3-(2-fluorophenyl)-5-isobutoxy Base-1,3,4-furodiindole-2(311)-嗣26.55 83.52 3-(4-Phenylphenyl)-5-(3-phenylpropoxy)_ 1,3,4- Furadiazole-2(311)-ketone 38.45 85.58 3-(4-Hydroxyphenyl)-5-(4-phenylbutoxy)-1,3,4-furadiazole-2(311)-one 65.84 95.66 3-(4-Hydroxyphenyl)-5-(6-phenylhexyloxy)-1,3,4-furadiazole-2(3H)-one 51.19 96.15 5-(2-Phenyl ethoxylate 3-(4-hydroxyphenyl)-1,3,4-furadiazole-2 (3-acetone 31.37 92.16 3-(4-Aminosulfonylphenyl)-5-(5- Phenylpentyloxy)-1,3,4-furadiazole-2(3H)-one 45.73 74.76 3-(4-Aminocarbonylphenyl)-5-(4-(4-fluorophenyl) Oxy)-1,3,4-furadiazole-2(3H)-one 59.61 106.79 3-(4-Amino-based phenyl)-5-(5-(4-phenylphenyl)pentyloxy -1,3,4-furadiazole-2(3H)-one 71.77 105.07 3-(4-Aminocarbonylphenyl)-5-(4-p-tolylbutoxy H,3,4- Furadiazole-2(3H)-one 30.46 68.63 3-(4-Aminocarbonylphenyl)-5-(5-phenylpentyloxy)-1,3,4-furadiazole-2 (3H) -ketone 56.07 84.41 5-(biphenyl-4-yloxy)-3-(4-carbylphenyl)_ 1,3,4-furadiazole-2(311)-one 17.29 62.46 5-(2 -Vinyloxy)-3-(4-decyloxyphenyl)-1,3,4-furadiazole-2(311)-one 44.98 88.26 5-(3,4-difluorophenoxy) -3-(4-methoxyphenyl)-1,3,4-furadiazole-2(3H)-one 49.6 85.72 1 23 200932732 5-(2-Fluorophenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(311)-one 44.44 93.98 5-(3,4-Difluoro Phenoxy)-3-(4-hydroxyphenyl)-1,3,4-furadiazole-2(311)-one 17.28 58.22 3-(3-Aminophenyl)-5-(2,4 -difluorophenoxy)-1,3,4-furadiazole-2(3H)-one 21.63 82.92 5-(4-Vephenoxy)-3-(3,4-dihydroxyphenyl)- 1,3,4-furadiazole-2(311)-ketone 4.94 83.36 5-(2,4-difluorophenoxy)-3-(3,4-dihydroxyphenyl)-1,3,4 -furadiazole-2(3H)-one 3.56 65.78 5-(2,4-difluorophenoxy)-3-(3-hydroxyphenyl)- 1,3,4-furadiazole-2 (311 )-ketone 11.85 93.77 5-(4-Benzyl phenyl)-3-(3-fluoro-4-phenylphenyl)- 1,3,4-furadiazole-2(3H)-one 49.56 86.55 5 -(4-chlorophenyl-lactyl)-3-(2- gas-4-3⁄4-ylphenyl)_ 1,3,4-furadiazole-2(3H)-one 3.8 64.34 5-(2,4- Difluorophenoxy)-3-(4-hydroxy-3-methylphenyl)-1,3,4-furadiazole-2 (3 - ketone 10.23 48.25 5-(4-phenoxy) -3-(4-hydroxy-3-methylphenyl)-1,3,4-furadiazole-2(3H)-one 37.45 50.01 5-(2,4-difluorophenoxy)-3- (4-hydroxy-3,5-dimethylphenyl)-1,3,4-furadiazole-2(311)-ketone 7.58 67.44 5-(2,4-difluorophenoxy)-3- (4-(3-methoxy) Benzyloxy)phenyl)-1,3,4-furadiazole-2(311)-one 45.86 96.03 3-(4-Benzylnonyloxyphenyl)-5-(4-phenoxy) -1,3,4-furadiazole-2(3H)-one 108.8 94.4 3-(4-Ethyloxyphenyl)-5-(2,4-difluorophenoxy)-1,3, 4-furadiazole-2(3H)-one 73.67 96.55 3-(4-Isobutylguanidinooxyphenyl)-5-(2,4-difluorophenoxy)-1,3,4-furadiazole- 2(3H)-ketone 55.9 90.41 5-(2,4-difluorophenoxy)-3-(7-pyridyl-2-yl)-1,3,4-furadiazole-2(3H) -ketone 79.41 86.37 3-(4-Amino-3-methyllacylphenyl)-5-(2,4-dioxaphenyloxy)-1,3,4-furadiazole-2(3H)- Ketone hydrochloride 4.19 9.61 3-(4-Amino-3-(2-methoxyethoxy)phenyl)-5-(2,4-difluorophenoxy)-1,3,4- Furadiazole-2(3H)-one 4.99 6.76 As evident from the above tests, all are characterized by a 5-0-substituted 3-N-phenyl-1,3,4-furadiazolone structural unit. The compounds of the invention, which have an unexpectedly high level of FAAH inhibition, make these novel compounds a potential candidate for the treatment or prevention of FAAH-associated medical conditions. Moreover, this unexpectedly high FAAH inhibition is evident not only in the test tube 200932732, but also in vivo. Moreover, a comparison of in vivo data also shows that the FAAH inhibitory activity of a compound having a 5 〇 _ substituted 3-N-phenyl-1,3,4-» bis-pyrone structure is characterized by a phase It has a selectivity for peripheral nerves compared to the activity of the central nervous system (CNS). The above data for a wide range of highly active compounds shows that the 5-O-substituted 3-N-phenyl-1,3,4-indenyl dispotonone structural unit of the following formula (III): 0

(III) 係-種用於抑制FAAH之強力的藥效基團，及對於存在於該藥效基财的取代基之選擇方面具有高度的可變性。應瞭解在所附申請專利範圍的範嘴内，可修御本發明。 C圖式簡單明;j (無）【主要元件符號說明】 (無） 125(III) A pharmacological group for inhibiting the potency of FAAH, and a high degree of variability in the selection of substituents which are present in the pharmacological potency. It will be appreciated that within the scope of the appended claims, the invention may be practiced. C pattern is simple and clear; j (none) [main component symbol description] (none) 125

Claims

200932732 七、申請專利範圍： 1. 一種具化學式(I)的化合物：200932732 VII. Patent application scope: 1. A compound of formula (I):

(I) 5 其中 R1至R5係彼此獨立地代表：(I) 5 where R1 to R5 are independent of each other:

氫； CVCV烷基、c3-c8-環烷基、c6-c1()-芳基、c6-c10-芳基-crc8-烷基、CrCV烷氧基、c6-c1()-芳氧基、 10 C6_Ci〇-芳基-Ci-C8_ 烧氧基、Ci_C6-烧氧基叛基、C6-Ci〇_Hydrogen; CVCV alkyl, c3-c8-cycloalkyl, c6-c1()-aryl, c6-c10-aryl-crc8-alkyl, CrCV alkoxy, c6-c1()-aryloxy, 10 C6_Ci〇-aryl-Ci-C8_ alkoxy, Ci_C6-alkyloxy, C6-Ci〇_

芳氧基羰基、c6-c1()-芳基-crc8-烷氧基羰基、crc6-烷基羰基、C6-C1()-芳基羰基、C6-C1()-芳基-CkCV烷基羰基、Q-C6-烷基羧基、C6-C1Q-芳基羧基、Ci-CV烷基氫硫基、C6-Ci〇-芳基氯硫基、Ci_C6-烧基魏基幾基、 15 C3-C8-環烷基酼基羰基、C6-C!。-芳基巯基羰基、CrC6- 烷基毓基羧基、c6-c1Q-芳基酼基羧基、crc6-烷基磺醯基、c6-c10-芳基磺醯基、crc6-烷基氧硫基、c6-c1(r芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次： crc6-烷基；crc6-烷氧基；c6-c1()-芳氧基； 20 co2h ; so3h ; conh2 ; so2nh2 ； CONH2 或 S〇2NH2，其中該胺基官能度被選自CVCV烷基、 c6-c10-芳基或C6-C10-芳基-CVQ-烷基的殘基取代一 126 200932732 5Aryloxycarbonyl, c6-c1()-aryl-crc8-alkoxycarbonyl, crc6-alkylcarbonyl, C6-C1()-arylcarbonyl, C6-C1()-aryl-CkCV alkylcarbonyl , Q-C6-alkylcarboxy, C6-C1Q-arylcarboxy, Ci-CV alkylthiol, C6-Ci〇-arylthiothio, Ci_C6-alkylthiomethyl, 15 C3-C8 - cycloalkylcarbonylcarbonyl, C6-C!. -arylcarbonylcarbonyl, CrC6-alkyldecylcarboxy, c6-c1Q-aryldecylcarboxy, crc6-alkylsulfonyl, c6-c10-arylsulfonyl, crc6-alkyloxythio, C6-c1 (raryloxythio, each of which is optionally substituted one or more times by: crc6-alkyl; crc6-alkoxy; c6-c1()-aryloxy; 20 co2h ; so3h ; conh2 ; so2nh2 ; CONH2 or S〇2NH2, wherein the amino functionality is substituted by a residue selected from a CVCV alkyl group, a c6-c10-aryl group or a C6-C10-aryl-CVQ-alkyl group. 200932732 5

次或多次，及其中在一種經二-cvcv烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6-烷基、C6-C1(r芳基、C6-C10-芳基-CrC4-烷基、CrCV烷基羰基、C6-C1()-芳基羰基、Ci-CV烷基石黃酿基及C6-ClQ-方基確酿基，硫鼠基，經基，石肖基；氰基；氟代基；氯代基；溴代基；碘代基；cf3 或 ocf3 ; co2h ； 10 so3h ; 15 胺基；經選自下列群中的殘基取代一或多次之胺基： crc6-烷基、C6-C10-芳基、C6-C1()-芳基-CrCV烷基、 CrC6-烷基羰基、C6-C1()-芳基羰基、Q-C6-烷基磺醯基及C6_Ci〇_方基續酿基，具下列化學式(II)之一種經二取代的胺基：One or more times, and in the case of a di-cvcv alkyl-substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; selected from the group consisting of One or more amino groups substituted with a residue: CrC6-alkyl, C6-C1 (r aryl, C6-C10-aryl-CrC4-alkyl, CrCV alkylcarbonyl, C6-C1()-arylcarbonyl , Ci-CV alkyl yellow wine base and C6-ClQ-square base, sulfur mouse, meridine, schiffyl; cyano; fluoro; chloro; bromo; iodo; cf3 or Off3 ; co2h ; 10 so3h ; 15 Amino; an amine group substituted one or more times with a residue selected from the group consisting of: crc6-alkyl, C6-C10-aryl, C6-C1()-aryl- CrCV alkyl, CrC6-alkylcarbonyl, C6-C1()-arylcarbonyl, Q-C6-alkylsulfonyl and C6_Ci〇-aryl, having a disubstituted form of the following formula (II) Amino group:

Γ~\ -Ν WΗ7] L Jo (II) 其中O代表0或1，而w代表氧、CH2或NR6，R6係選自氫與Q-CV烷基，及其中化學式(II)中的亞甲基可選擇性地被CrCV烷基、氟代基或氣代基取代一或二次； conh2 ; so2nh2 ； conh2或so2nh2，其中該胺基官能度被選自 127 20 200932732 CrCV烷基、c6-c1(r芳基或cvc!。-芳基-crc6-烷基的殘基取代一或二次，及其中在一種經二-CrCA-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或 6員環； 5 硫氫基；羥基；墙基；氰基；氟項醢基； ◎ 10 選自氟代基、氣代基、溴代基或碘代基之鹵素； CF3 ; 0CF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次： 15 Ci-C6_ ，Ci-C6_ ，COOH，SO3H， conh2 ; so2nh2 ; conh2或so2nh2，其中該胺基官能度被選自CkCV烷基、c6-c1(r芳基或c6-c1(r芳基 ® -crc4-烷基的殘基取代一次或多次，及其中在一種經二-crc6-烷基取代的胺基官能度之情況下，該烷基 20 殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、c6-c10-芳基、C6-C10-芳基-Q-C4-烷基、crc6-烷基羰基、 c6-c1(r芳基羰基、crc6-烷基磺醯基及c6-c1(r芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代 128 200932732 基；溴代基；碘代基；CF3或OCF3 ; 及其中R1至R5中之任二或多者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統； η代表0或1 ; m代表0、1、2、3、4、5或6 ; 5 X代表氧或硫； Y代表： a) 氫； Ο 10 15 ⑩ 20 b) Ci-C!8_烧基、早元不飽和或多元不飽和C2_Ci8_ 亞烷基、c3-c8-環烷基、c6-c1()-芳基、c6-c1(r芳基 -Ci-Cr烧基、Ci_C6_烧氧基、C6-Ci〇-芳氧基、C6_Ci〇-芳基-Q-CV烷氧基、CrCV烷氧基羰基、C6-C1(r芳氧基羰基、C6-Ci〇-方基-Ci_C8-烧氧基幾基、Ci_C6-烧基幾基、 C6-C1()-芳基羰基、C6-C1()-芳基-CVC8-烷基羰基、CVCV 烷基羧基、c6-c1()-芳基羧基、crc6-烷基氫硫基、 C6-C1()-芳基氫硫基、CkCV烷基酼基羰基、c3-c8-環烷基巯基羰基、C6-C1G-芳基巯基羰基、Q-C6-烷基巯基羧基、c6-c1()-芳基酼基羧基、crc6-烷基磺醯基、c6-c10-芳基磺醯基、crc6-烷基氧硫基、c6-c1(r芳基氧硫基或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其中各者選擇性地被下列各者取代一次或多次： bDCrCV烷基、C3-C8-環烷基、C6-C1()-芳基、 C6_Ci〇-芳基-C「C8-烧基、Ci-C6-烧氧基、C6_Ci〇-芳氣基、C6-C1()-芳基-CrC8-烷氧基、CVC6-烷氧基羰基、 C6-C1Q-芳氧基羰基、C6-C1Q-芳基-CVC8-烷氧基羰 129 200932732 基、crc6-烷基羰基、c6-c10-芳基羰基、c6-c10-芳基 -CrCV烷基羰基、crc6-烷基羧基、c6-c1C)-芳基羧基、Ci-Cf炫基風硫基、C6-Ci〇-芳基氮硫基、Ci-C^-烷基酼基羰基、c3-c8-環烷基巯基羰基、c6-c1(r芳基 5 巯基羰基、CrC6-烷基巯基羧基、C6-C1Q-芳基酼基羧基、crc6-烷基磺醯基、c6-c1(r芳基磺醯基、crc6-烷基氧硫基、c6-c1(r芳基氧硫基；其中各者選擇性地被下列各者取代一次或多次：CVC6-烷基；CrC6-烷氧基；CONH2、S02NH2 ;其中該胺基官能度被 © 10 CVC6-烷基取代一次或二次之CONH2或S02NH2 ; so3h ; co2h ;胺基；經選自下列群中的殘基取代一 ' 或多次之胺基：Ci-CV烷基、c6-c10-芳基、c6-c10-芳 . 基-CVC6-烷基、Q-C6-烷基羰基、c6-c1()-芳基羰基、 Ci_C6_烧基續酿基及C6-Ci〇-芳基績酿基；硫氮基；經 15 基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；CF3 ;或 OCF3 ; 其中bl)中的數個取代基可結合而形成稠合的飽 ® 和、不飽和或芳族同環或雜環系統；或被： 20 b2)羥基；硫氫基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；cf3 ; co2h ; S03H ; OCF3 ; conh2 ; so2nh2 ; conh2或so2nh2，其中該胺基官能度被選自Q-C6-烷基、C6-C10-芳基或C6-C10-芳基 -CrCV烷基的殘基取代一或二次，及其中在一種經二 130 200932732Γ~\ -Ν WΗ7] L Jo (II) wherein O represents 0 or 1, and w represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and Q-CV alkyl, and the methylene group in the formula (II) The group may be optionally substituted by a CrCV alkyl, fluoro or ke group for one or two times; conh2; so2nh2; conh2 or so2nh2, wherein the amine functionality is selected from 127 20 200932732 CrCV alkyl, c6-c1 The residue of (raryl) or cvc!-aryl-crc6-alkyl is substituted one or two times, and in the case of a di-CrCA-alkyl substituted amine functionality, the alkyl residue The group may be combined to form a 5 or 6 membered ring; 5 sulfhydryl; hydroxy; wall group; cyano; fluoro fluorenyl; ◎ 10 halogen selected from fluoro, carbyl, bromo or iodo ; CF3 ; 0CF3 ; or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, which is optionally substituted one or more times by: 15 Ci-C6_ , Ci-C6_ , COOH, SO3H, conh2; so2nh2; conh2 or so2nh2, wherein the amino functionality is replaced by a residue selected from the group consisting of CkCV alkyl, c6-c1 (r aryl or c6-c1 (raryl®-crc4-alkyl) One or more times, and in the case of a di-crc6-alkyl substituted amine functionality, the alkyl 20 residue may be combined to form a 5 or 6 membered ring; an amine group; selected from the group consisting of The residue in the group is substituted with one or more amine groups: crc6-alkyl, c6-c10-aryl, C6-C10-aryl-Q-C4-alkyl, crc6-alkylcarbonyl, c6-c1 (r Arylcarbonyl, crc6-alkylsulfonyl and c6-c1 (rarylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; gas 128, 200932732; bromo; a substituent; CF3 or OCF3; and any two or more of R1 to R5 thereof may be combined to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; η represents 0 or 1; m represents 0, 1, 2, 3, 4, 5 or 6; 5 X represents oxygen or sulfur; Y represents: a) hydrogen; Ο 10 15 10 20 b) Ci-C! 8_alkyl, early unsaturated or polyunsaturated C2_Ci8_alkylene, c3-c8-cycloalkyl, c6-c1()-aryl, c6-c1 (raryl-Ci-Cr alkyl, Ci_C6_alkoxy, C6-Ci〇-aryloxy , C6_Ci〇-aryl-Q-CV alkoxy, CrCV alkoxycarbonyl, C6-C1 (r aryloxycarbonyl, C6-Ci〇-square-Ci_C8- Oxyl group, Ci_C6-alkyl group, C6-C1()-arylcarbonyl, C6-C1()-aryl-CVC8-alkylcarbonyl, CVCV alkylcarboxy, c6-c1()-aryl Carboxyl group, crc6-alkylthiol group, C6-C1()-arylhydrothio group, CkCV alkylmercaptocarbonyl group, c3-c8-cycloalkylfluorenylcarbonyl group, C6-C1G-aryldecylcarbonyl group, Q- C6-alkylmercaptocarboxy, c6-c1()-aryldecylcarboxy, crc6-alkylsulfonyl, c6-c10-arylsulfonyl, crc6-alkyloxythio, c6-c1 (r An aryl oxythio group or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, each of which is optionally substituted one or more times by: bDCrCV alkyl, C3-C8 -cycloalkyl, C6-C1()-aryl, C6_Ci〇-aryl-C "C8-alkyl, Ci-C6-alkoxy, C6_Ci〇-aryl, C6-C1()-aryl -CrC8-alkoxy, CVC6-alkoxycarbonyl, C6-C1Q-aryloxycarbonyl, C6-C1Q-aryl-CVC8-alkoxycarbonyl 129 200932732, rc6-alkylcarbonyl, c6-c10- Arylcarbonyl, c6-c10-aryl-CrCV alkylcarbonyl, crc6-alkylcarboxy, c6-c1C)-arylcarboxy, Ci-Cf phosgene, C6-Ci〇-arylsulfur , Ci-C^-alkylmercaptocarbonyl, c3-c8-cycloalkylfluorenylcarbonyl, c6-c1 (raryl 5 fluorenylcarbonyl, CrC6-alkylindenylcarboxy, C6-C1Q-aryldecylcarboxyl, Crc6-alkylsulfonyl, c6-c1 (rarylsulfonyl, crc6-alkyloxythio, c6-c1 (raryloxythio; each of which is optionally substituted once by each of the following) Or multiple times: CVC6-alkyl; CrC6-alkoxy; CONH2, S02NH2; wherein the amine functionality is replaced by 10 CVC6-alkyl one or two times CONH2 or S02NH2; so3h; co2h; amine group; Substituents selected from the group consisting of one or more amine groups: Ci-CV alkyl, c6-c10-aryl, c6-c10-aryl.yl-CVC6-alkyl, Q-C6-alkyl Carbonyl, c6-c1()-arylcarbonyl, Ci_C6_alkyl aryl and C6-Ci〇-aryl base; sulfur nitrogen; 15 base; nitro; cyano; fluoro; a substituent; a bromo group; an iodo group; CF3; or OCF3; wherein a plurality of substituents in bl) may combine to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; : 20 b2) hydroxy; sulfhydryl; nitro; cyano; fluoro; chloro; bromo Base; iodo group; cf3; co2h; S03H; OCF3; conh2; so2nh2; conh2 or so2nh2, wherein the amine functionality is selected from the group consisting of Q-C6-alkyl, C6-C10-aryl or C6-C10-aryl The residue of the base-CrCV alkyl group is substituted one or two times, and one of them is in one of the two 130 200932732

5 -CrCV烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：CVC6-烷基、C6-C10-芳基、c6-c1(r芳基-CrC8-烷基、CrC6-烷基羰基、C6-C10-芳基羰基、Q-CV烷基磺醯基及C6-C1()-芳基磺醢基；或具下列化學式(II)之一種經二取代的胺基： ❹ Γ~\ —N W Η7] ° (II) 其中0代表〇或1，而W代表氧、CH2或NR6，R6係選自氫與CrC6-烷基，及其中化學式(II)中的亞甲基可選擇 10 性地被CrC6-烷基、氟代基或氯代基取代一或二次；或被： b3)—種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次：CVCV烷基；CVC6-烷氧基；COOH ; S03H ; 15 ❹ conh2 ; so2nh2 ; conh2或so2nh2，其中該胺基官能度被選自crc6-烷基、c6-c1(r芳基或c6-c1(r芳基 -Q-Cr烷基的殘基取代一次或多次，及其中在一種經二-CKC6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群 20 中的殘基取代一或多次之胺基：CVCV烷基、C6-C10-芳基、CVC〗。-芳基-Ci-Q-烷基、CVCV烷基羰基、 c6-c1()-芳基羰基、CrC6-烷基磺醯基及C6-C1()-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氯代 131 200932732 基；溴代基；碘代基；CF3或OCF3 ; C)S03H ;胺基；經選自下列群中的殘基取代一或多次之胺基：CVQ-烷基、C6-C10-芳基、C6-C10-芳基 _Ci_C8-烧基、Ci_C6-烧基幾基、CfCio-芳基叛基、 5 CrCV烷基磺醯基及CVCi。-芳基磺醯基；CONH2 ; S02NH2; C0NHdS02NH2,其中該胺基官能度被選自 CrC6-烷基、C6-C1(r芳基或C6-C1(r芳基-CVC6-烷基的殘基取代一或二次，及其中在一種經二-CrC^-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員 10 環；硫氫基；羥基；硝基；氰基；氟磺醯基；選自氟代基、氣代基、溴代基或碘代基之i素；cf3 ;或〇CF3 ；或其一種立體異構物、藥學上可接受的鹽類或酯或前驅藥物，以用於抑制脂肪酸醯胺水解酶(FAAH)。 15 2.如申請專利範圍第1項之化合物，其中R1至R5係彼此獨立地代表：氫；羥基； crc6-烷基、c6-c1(r芳基、crc6-烷氧基、c6-c10-20 芳氧基、C6-C10-芳基-Ci-CV烷氧基、Ci-CV烷基羧基、 C6-C1()-芳基羧基、Q-C6-烷基磺醯基、c6-c1(r芳基磺醯基，其中各者選擇性地被下列各者取代一次或多次： Ci_C6-烧基、C!-C6-烧氧基、胺基、Ci_C6-烧基胺基、二-CVCV烷基胺基、羥基、氟代基、氯代基、溴代 200932732 基、氰基、CF3或OCF3 ; 胺基；經選自Q-C6-烷基、c6-c10-芳基的殘基取代一或多次之胺基； 1-吡咯基、2-吡咯基或3-吡咯基，其選擇性地被一或多個選自CrC6-烷基、胺基、氟代基、氣代基或CF3之殘基取代；或具下列化學式(II)之一種經二取代的胺基： ❹ ❹ ° (II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選 10 自氫與Ci-CV烷基，及其中化學式(II)中的亞曱基可選擇性地被CVCV烷基、氟代基或氣代基取代一或二次； CONH2 ; so2nh2 ； CONH2或S02NH2，其中該胺基官能度被選自cr 15 c6-烷基或c6-c1(r芳基的殘基取代一或二次；氟代基；氯代基；溴代基； CF3 ;或 20 OCF3。 3. 如申請專利範圍第1或2項之化合物，其中R1至R5中之一或多者代表氫、氟或氯。 4. 如申請專利範圍第3項之化合物，其中R1或R5代表氫或氟。 133 200932732 5. 如申請專利範圍第1至4項中任一項之化合物，其中R1 至R5中之一或多者代表：羥基；或 crc6-烷氧基、c6-c10-芳氧基、c6-c10-芳基-crc6-5 烧氧基、Ci_C6_烧基叛基、C6_Ci〇-芳基叛基、Ci_C6_烧基磺醯基、c6-c1()-芳基磺醯基，其中各者選擇性地被下列各者取代一次或多次：CVC6-烷基、crc6-烷氧基、胺基、CrCV烷基胺基、二-crc6-烷基胺基、選擇性地被Ci-CV烷基或Q-Ci。-芳基取代一或二次之CONH2或 10 so2NH2、羥基、氟代基、氯代基、溴代基、氰基、 CF3 或 OCF3。 6. 如申請專利範圍第5項之化合物，其中R2、R3或R4中之一者代表：羥基；或 15 CVCV烷氧基、C6-C1(r芳氧基或C6-C1(r芳基-Q-CV 烷氧基，其中各者選擇性地被下列各者取代一或多次： CVCV烷基、CrC6-烷氧基、胺基、CVC6-烷基胺基、二-CrC6-烷基胺基、選擇性地被CVCV烷基或C6-C10-芳基取代一或二次之conh2或so2nh2、羥基、氟代基、 20 氣代基或溴代基。 7. 如申請專利範圍第1至6項中任一項之化合物，其中R1 至R5中之一或多者代表：胺基；經選自CrCV烷基、C6-C10-芳基的殘基取代一或多 200932732 次之胺基；或具下列化學式(II)之一種經二取代的胺基： 5 —N W Η7] ° (II) 其中0代表〇或1，而W代表氧、CH2或NR6，R6係選自氫與Q-cv烷基，及其中化學式(II)中的亞甲基可選擇 ❹ 性地被Ci-CV烧基、氟代基或氣代基取代一或二次。 8.如申請專利範圍第7項之化合物，其中R2、R3或R4中之一者代表：胺基； 10 被選自CVC6-烷基、C6-C1(r芳基的殘基取代一或二次之胺基；或 Ο 15 具下列化學式(II)之一種經二取代的胺基： Γ~\ —N W Η7] ° (II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-C6-烷基，及其中化學式(II)中的亞甲基可選擇性地被CrC6-烷基、氟代基或氣代基取代一或二次。 9.如申請專利範圍第1至8項中任一項之化合物，其中η代表0 ; m代表0、1、2、3、4、5或6 ;及Υ代表C3-C6-環烷基或C6-C1(r芳基，其中各者選擇性地被下列各者取 20 代一或多次： a)Ci-C6-烧基、C6-Ci〇-芳基、C6-Ci〇-芳基-C1-C4-烧基、CrC6-烷氧基、C6-C1()-芳氧基、C6-C1()-芳基-CrC4-烷 135 200932732 氧基，其中各者選擇性地被下列各者取代一次或多次： Q-CV烷基；CrC6-烷氧基；COOH ; CONH2 ; so2nh2 ;被crc6-烷基或c6-c10-芳基取代一或二次之conh2或so2nh2 ; so3h ;胺基；經選自下列群中 5 的殘基取代一或多次之胺基：CVCV烷基、C6-C10-芳In the case of 5-CrCV alkyl-substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; one or more amine groups substituted with a residue selected from the group consisting of :CVC6-alkyl, C6-C10-aryl, c6-c1 (raryl-CrC8-alkyl, CrC6-alkylcarbonyl, C6-C10-arylcarbonyl, Q-CV alkylsulfonyl and C6 -C1()-arylsulfonyl; or a disubstituted amino group of the following formula (II): ❹ Γ~\ -NW Η7] ° (II) where 0 represents 〇 or 1, and W represents oxygen , CH2 or NR6, R6 is selected from the group consisting of hydrogen and CrC6-alkyl, and the methylene group in the formula (II) may be optionally substituted one or two times by CrC6-alkyl, fluoro or chloro group. Or by: b3) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, which is optionally substituted one or more times by: CVCV alkyl; CVC6-alkoxy (COOH; S03H; 15 ❹ conh2 ; so2nh2 ; conh2 or so2nh2, wherein the amine functionality is selected from the group consisting of crc6-alkyl, c6-c1 (r aryl or c6-c1 (r aryl-Q-Crane) The residue of the group is substituted one or more times, and in one of the di-CKC6-alkanes In the case of a substituted amino functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; one or more amine groups substituted with a residue selected from the group 20 below: CVCV alkane , C6-C10-aryl, CVC. -Aryl-Ci-Q-alkyl, CVCV alkylcarbonyl, c6-c1()-arylcarbonyl, CrC6-alkylsulfonyl and C6-C1 ( )-arylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; chloro131 200932732; bromo; iodo; CF3 or OCF3; C) S03H; One or more amino groups substituted with a residue selected from the group consisting of CVQ-alkyl, C6-C10-aryl, C6-C10-aryl-Ci_C8-alkyl, Ci_C6-alkyl, CfCio- Aryl-rebase, 5 CrCV alkylsulfonyl and CVCi.-arylsulfonyl; CONH2; S02NH2; C0NHdS02NH2, wherein the amine functionality is selected from the group consisting of CrC6-alkyl, C6-C1 (r-aryl or The C6-C1 (r-aryl-CVC6-alkyl residue is substituted one or two times, and in the case of a di-CrC-alkyl-substituted amine functionality, the alkyl residue can be combined And forming 5 or 6 members of 10 rings; sulfhydryl; hydroxy; nitro; cyano; fluorosulfonyl; a fluoro, an alkenyl, a bromo or iodo group; a cf3; or a guanidine CF3; or a stereoisomer thereof, a pharmaceutically acceptable salt or ester or a prodrug thereof, for use in inhibition Fatty acid guanamine hydrolase (FAAH). 15. The compound of claim 1, wherein R1 to R5 are independently of each other: hydrogen; hydroxy; crc6-alkyl, c6-c1 (raryl, crc6-alkoxy, c6-c10- 20 aryloxy, C6-C10-aryl-Ci-CV alkoxy, Ci-CV alkylcarboxy, C6-C1()-arylcarboxy, Q-C6-alkylsulfonyl, c6-c1 ( Rarylsulfonyl, each of which is optionally substituted one or more times by: Ci_C6-alkyl, C!-C6-alkoxy, amine, Ci_C6-alkylamino, di-CVCV Alkylamino, hydroxy, fluoro, chloro, bromo 200932732, cyano, CF3 or OCF3; amine; substituted with a residue selected from Q-C6-alkyl, c6-c10-aryl One or more amine groups; 1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, optionally selected from one or more selected from the group consisting of CrC6-alkyl, amine, fluoro, valyl or Substituted by a residue of CF3; or a disubstituted amino group of the following formula (II): ❹ ❹ ° (II) wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen And a Ci-CV alkyl group, and the fluorenylene group in the formula (II) thereof can be selectively used by CVCV Substituting an alkyl group, a fluoro group or a gas group for one or two times; CONH2; so2nh2; CONH2 or S02NH2, wherein the amine functionality is selected from the group consisting of cr 15 c6-alkyl or c6-c1 (r-aryl) Substituting one or two; fluoro group; chloro group; bromo group; CF3; or 20 OCF3. 3. A compound according to claim 1 or 2, wherein one or more of R1 to R5 represents hydrogen 4. A compound of claim 3, wherein R1 or R5 represents hydrogen or fluorine. 133 200932732 5. A compound according to any one of claims 1 to 4, wherein R1 to R5 One or more of them represent: hydroxy; or crc6-alkoxy, c6-c10-aryloxy, c6-c10-aryl-crc6-5 alkoxy, Ci_C6_alkyl group, C6_Ci〇-aryl a base group, a Ci_C6-alkylsulfonyl group, a c6-c1()-arylsulfonyl group, each of which is optionally substituted one or more times by: CVC6-alkyl, crc6-alkoxy , Amino, CrCV alkylamino, di-crc6-alkylamino, optionally substituted by Ci-CV alkyl or Q-Ci.-aryl, one or two times of CONH2 or 10 so2NH2, hydroxyl, fluorine Substituted, chlorinated , bromo, cyano, CF3 or OCF3. 6. A compound according to claim 5, wherein one of R2, R3 or R4 represents: hydroxy; or 15 CVCV alkoxy, C6-C1 (r An aryloxy group or a C6-C1 (raryl-Q-CV alkoxy group, each of which is optionally substituted one or more times by: CVCV alkyl, CrC6-alkoxy, amine, CVC6- Alkylamino, di-CrC6-alkylamino, optionally substituted by CVCV alkyl or C6-C10-aryl, one or two times of conh2 or so2nh2, hydroxy, fluoro, 20, or bromo Daiji. 7. The compound of any one of claims 1 to 6, wherein one or more of R1 to R5 represents: an amine group; substituted with a residue selected from the group consisting of CrCV alkyl and C6-C10-aryl One or more of 200932732 amino groups; or a disubstituted amino group of the following formula (II): 5-NW Η7] ° (II) wherein 0 represents hydrazine or 1, and W represents oxygen, CH2 or NR6, R6 is selected from the group consisting of hydrogen and Q-cv alkyl, and the methylene group in the chemical formula (II) may be optionally substituted one or two times with a Ci-CV alkyl group, a fluoro group or a gas group. 8. A compound according to claim 7 wherein one of R2, R3 or R4 represents: an amine group; 10 is substituted with one or two residues selected from the group consisting of CVC6-alkyl and C6-C1 (r-aryl) Amino group; or 15 a disubstituted amino group of the following formula (II): Γ~\ —NW Η7] ° (II) wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R6 is selected from the group consisting of hydrogen and Q-C6-alkyl, and the methylene group of the formula (II) thereof may be optionally substituted one or two times with a CrC6-alkyl group, a fluoro group or a gas group. The compound of any one of claims 1 to 8, wherein η represents 0; m represents 0, 1, 2, 3, 4, 5 or 6; and Υ represents C3-C6-cycloalkyl or C6-C1 (raryl), each of which is optionally taken one or more times by 20 generations: a) Ci-C6-alkyl, C6-Ci〇-aryl, C6-Ci〇-aryl-C1- C4-alkyl, CrC6-alkoxy, C6-C1()-aryloxy, C6-C1()-aryl-CrC4-alkane 135 200932732 oxy, each of which is optionally substituted once by Or multiple times: Q-CV alkyl; CrC6-alkoxy; COOH; CONH2; so2nh2; substituted by crc6-alkyl or c6-c10-aryl Or a second conh2 or so2nh2; so3h; an amine group; an amine group substituted one or more times by a residue selected from the group consisting of CVCV alkyl, C6-C10-aryl

基、C6-C!〇-芳基-CrC4-烧基、Ci-C6_烧基幾基、 c6-c1(r芳基羰基、crc6-烷基磺醯基及c6-c1()-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；CF3或OCF3 ; 10 或被： b)羥基；硫氫基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；cf3 ; ocf3 ; co2h ; so3h ; conh2 ; so2nh2 ; conh2或so2nh2，其中該胺基官能度被選自Crc6-烷基、c6-c1(r芳基或c6-c1()-芳基 15 -Ci-C4_炫基的殘基取代一次或多次’及其中在一種經二, C6-C! 〇-aryl-CrC4-alkyl, Ci-C6-alkyl, c6-c1 (rarylcarbonyl, crc6-alkylsulfonyl and c6-c1()-aryl Sulfhydryl; sulfhydryl; hydroxy; nitro; cyano; fluoro; carbyl; bromo; iodo; CF3 or OCF3; 10 or by: b) hydroxy; sulfhydryl; Cyano; fluoro; ketone; bromo; iodo; cf3; ocf3; co2h; so3h; conh2; so2nh2; conh2 or so2nh2, wherein the amine functionality is selected from the group consisting of Crc6-alkyl, C6-c1 (r-aryl or c6-c1()-aryl 15-Ci-C4_thrylenyl residue substituted one or more times' and

-CrC6·烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；被Cl_c6_烷基或苯基取代一或多次之胺基；具下列化學式(II)之一種經二取代的胺基：In the case of a -CrC6.alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times with a Cl_c6-alkyl or phenyl group; a disubstituted amino group of the following formula (II):

其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與CnCr烧基，及其中化學式⑼中的亞甲基可選擇性地被G-Cr烷基、氟代基或氣代基取代一或二次； 136 200932732 或被： c) 一種由至多10個原子組成之飽和、不飽和或务族雜環式環系統，其選擇性地被下列各者取代一或多次： 5 CVQ-烷基；CrC6-烷氧基；COOH ; CONH2 ; S02NH2 ;被。-。-烷基或C6-C10-芳基取代一或二次之conh2或so2nh2 ; so3h ;胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、c6-c10-芳基、C6_Ci〇-芳基-C1-C4-烧基、Ci-C6-烧基幾基、C6-Ci〇- 0 芳基羰基、crc6-烷基磺醯基及c6-c1()-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；CF3或OCF3。 1〇·如申請專利範圍第9項之化合物，其中η代表0 ; m代表〇 $ 或1 ;及Y代表一個苯基、卜萘基、2-萘基、2-»比淀基、 3、°比啶基或4-吡啶基環系統。 U*如申請專利範圍第10項之化合物，其中γ被下列各者取代一或多次：CrCV院基；苯基；crC6-烧氧基；經基；氟代基；氯代基；溴代基；CF3 ; 〇CF3 ;胺基；或〇選擇性地被Cj-CV烧基取代一或二次之c〇nh2或 ShNH2,其中該等選擇性的Cl-cv燒基殘基可結合而形成5或6員環。如申请專利範圍第11項之化合物，其代表〇，及γ代表被經基、氟代基、氯代基或漠代基取代一或二次之苯基。 13·如申請專利範圍第11項之化合物，其中m代表〇,及γ代 137 200932732 表苯基，其在4-位置被氟代基或被氣代基取代、在2-與 4-位置被氟代基取代、在2-與4-位置被氣代基取代或在 4-位置被苯基取代。 14. 如申請專利範圍第丨項之化合物，其中m為〇 ; n為〇 ; γ 5 代表被氟代基、氣代基或溴代基取代一或二次之苯基；及R2至R4中之任一者代表0R7，其中R7係選自氫與 Ci-Cy烧基。 15. 如申請專利範圍第14項之化合物，其中γ代表苯基，其在4-位置被氟代基或被氣代基取代、在2與4_位置被氟 1〇代基取代或在2-與4-位置被氣代基取代。 16. 如申請專利範圍第14或15項之化合物，其中r1*r5代表氫或氟。 17. 如申請專利範圍第至16項中任一項之化合物，其中R2 或R3與R4代表羥基。 15 I8.如申請專利範圍第1至Π項中任一項之化合物，用於治療因FAAH抑制作用而受到正面影響之一病症。 19.如申請專利範圍第18項之化合物，其中該病症係選自疼痛，暈眩、嘔吐及噁心；飲食失調病症；神經與精神病變，急性與慢性神經退化性疾病；癲癇症；睡眠障礙； 20 心血管疾病；癌症；免疫系統病症；寄生蟲、病毒或細菌性傳染病；炎性疾病；骨質疏鬆症；眼部病況；肺部病況及胃腸疾病。 20·如申請專利範圍第1至Π項中任-項之化合物，用於抑制FAAH之用途。 200932732 21. 如申請專利範圍第1至17項中任一項之化合物，用於治療因FAAH抑制作用而受到正面影響的一病症之用途。 22. 如申請專利範圍第1至17項中任一項之化合物，用於製造一藥物之用途，該藥物係用於治療因FAAH抑制作用而受到正面影響的一病症。 ❹ ⑩ 15 23. 如申請專利範圍第21至22項之用途，其中該病症係選自疼痛；暈眩、嘔吐及噁心；飲食失調病症；神經與精神病變；急性與慢性神經退化性疾病；癲癇症；睡眠障礙；心血管疾病；癌症；免疫系統病症；寄生蟲、病毒或細菌性傳染病；炎性疾病；骨質疏鬆症；眼部病況；肺部病況及胃腸疾病。 24. —種具化學式(I)的化合物： P1 〇Wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and C nCr alkyl, and the methylene group in the formula (9) is optionally G-Cr alkyl, fluoro or Substituting one or two times for a gas radical; 136 200932732 or by: c) a saturated, unsaturated or branched heterocyclic ring system consisting of up to 10 atoms, which is optionally substituted one or more times by: : 5 CVQ-alkyl; CrC6-alkoxy; COOH; CONH2; S02NH2; -. - an alkyl or C6-C10-aryl group substituted one or two times of conh2 or so2nh2; so3h; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of: crc6-alkyl, c6- C10-aryl, C6_Ci〇-aryl-C1-C4-alkyl, Ci-C6-alkyl, C6-Ci〇- 0 arylcarbonyl, crc6-alkylsulfonyl and c6-c1() -arylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; ketone; bromo; iodo; CF3 or OCF3. 1. A compound of claim 9, wherein η represents 0; m represents 〇$ or 1; and Y represents a phenyl group, a naphthyl group, a 2-naphthyl group, a 2-» ratio of a decyl group, a ratio of 3, ° Pyridyl or 4-pyridyl ring system. U* is a compound of claim 10, wherein γ is substituted one or more times by: CrCV, phenyl, crC6-alkoxy; thiol; fluoro; chloro; bromo a group; CF3; 〇CF3; an amine group; or hydrazine optionally substituted by a Cj-CV alkyl group for one or two times c〇nh2 or ShNH2, wherein the selective Cl-cv alkyl group residues can be combined to form 5 or 6 member rings. A compound of claim 11, which represents hydrazine, and γ represents a phenyl group substituted one or two times with a fluoro, fluoro, chloro or hydroxy group. 13. A compound of claim 11 wherein m represents hydrazine and gamma 137 200932732 phenyl, which is substituted at the 4-position with a fluoro group or by a gas group, at the 2- and 4-positions The fluoro group is substituted, substituted with a gas group at the 2- and 4-positions or substituted with a phenyl group at the 4-position. 14. A compound according to the scope of claim 2, wherein m is hydrazine; n is hydrazine; γ 5 represents a phenyl group substituted one or two times by a fluoro, a gas or a bromo group; and R2 to R4 Any of them represents 0R7, wherein R7 is selected from the group consisting of hydrogen and Ci-Cy alkyl. 15. A compound according to claim 14, wherein γ represents a phenyl group which is substituted at the 4-position with a fluoro group or by a gas group, at the 2 and 4 positions by a fluorine 1 hydryl group or at 2 - Replacement with the 4-position by a gas group. 16. A compound as claimed in claim 14 or 15, wherein r1*r5 represents hydrogen or fluorine. 17. The compound of any one of claims 16 to 16, wherein R2 or R3 and R4 represent a hydroxy group. The compound of any one of claims 1 to 3 for use in the treatment of a condition which is positively affected by FAAH inhibition. 19. The compound of claim 18, wherein the condition is selected from the group consisting of pain, dizziness, vomiting, and nausea; eating disorders; neurological and psychiatric disorders, acute and chronic neurodegenerative diseases; epilepsy; sleep disorders; 20 cardiovascular disease; cancer; immune system disorders; parasitic, viral or bacterial infectious diseases; inflammatory diseases; osteoporosis; eye conditions; lung conditions and gastrointestinal diseases. 20. A compound as claimed in any of claims 1 to 3 for the purpose of inhibiting FAAH. The use of a compound according to any one of claims 1 to 17 for the treatment of a condition which is positively affected by FAAH inhibition. 22. The use of a compound according to any one of claims 1 to 17 for the manufacture of a medicament for the treatment of a condition which is positively affected by FAAH inhibition. ❹ 10 15 23. The use of paragraphs 21 to 22 of the patent application, wherein the condition is selected from the group consisting of pain; dizziness, vomiting and nausea; eating disorders; neurological and psychiatric disorders; acute and chronic neurodegenerative diseases; Symptoms; sleep disorders; cardiovascular disease; cancer; immune system disorders; parasitic, viral or bacterial infectious diseases; inflammatory diseases; osteoporosis; ocular conditions; pulmonary conditions and gastrointestinal diseases. 24. A compound of formula (I): P1 〇

N —Ο—(C=X)n—(CH2)m_Y (I) 其中 R1至R5係彼此獨立地代表：氫； Ci_C6-烧基、C3-C8-環烧基、C6-Ci〇-芳基、Cg-Cio-芳基-crc8-烷基、crc6-烷氧基、c6-c10-芳氧基、 C6-Ci〇-芳基-Ci_C8_烧氧基、Ci-C6·烧氧基幾基、C6-Ci〇_ 芳氧基羰基、c6-c1()-芳基-CVC8-烷氧基羰基、Q-cv烷基羰基、c6-c1()-芳基羰基、c6-c1(r芳基-crc8-烷基羰 139 20 200932732 基、CrCV烷基羧基、c6-c1()-芳基羧基、crc6-烷基氳硫基、C6-C10-芳基氫硫基、CrCr烷基酼基羰基、 c3-c8-環烷基酼基羰基、c6-c1(r芳基巯基羰基、crc6-烷基酼基羧基、C6-C1G-芳基巯基羧基、crc6-烷基磺醯 5 基、C6-C1()-芳基磺醯基、CrC6-烷基氧硫基、C6-C1(r芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次： CVC6-烷基；CrCV烷氧基；c6-c1()-芳氧基； co2h ； S03H ； CONH2 ； SO2NH2 ； CONH2 或 so2nh2，其中該胺基官能度被選自CVC6-烷基、〇 10 CVQ。-芳基或C6-C1(r芳基-Q-C4-烷基的殘基取代一次或多次，及其中在一種經二-Ci-Cr烷基取代的胺基 ‘ 官能度之情況下，該烷基殘基可結合而形成5或6員 ’ 環；胺基；經選自下列群中的殘基取代一或多次之胺基：CVC6-烷基、C6-C10-芳基、C6-C1()-芳基-CVC4-15 烷基、CVQ-烷基羰基、C6-C1(r芳基羰基、CVCV烷基績酿基及C6-Ci〇-芳基績酿基；硫氮基；經基；石肖基；氰基；氟代基；氣代基；溴代基；碘代基；cf3 ® 或 OCF3 ; co2h ； 20 SO3H ；胺基；經選自下列群中的殘基取代一或多次之胺基： Ci-CV烷基、C6-C10-芳基、C6-C1()-芳基-Ci-Q-烷基、 crc6-烷基羰基、C6-C1()-芳基羰基、CVCV烷基磺醯基 140 200932732 及C6-C10-芳基磺醯基；具下列化學式(II)之一種經二取代的胺基： —N WN—Ο—(C=X)n—(CH2)m_Y (I) wherein R1 to R5 are independently of each other: hydrogen; Ci_C6-alkyl, C3-C8-cycloalkyl, C6-Ci〇-aryl , Cg-Cio-aryl-crc8-alkyl, crc6-alkoxy, c6-c10-aryloxy, C6-Ci〇-aryl-Ci_C8_alkoxy, Ci-C6·alkoxy , C6-Ci〇_ aryloxycarbonyl, c6-c1()-aryl-CVC8-alkoxycarbonyl, Q-cv alkylcarbonyl, c6-c1()-arylcarbonyl, c6-c1(r-aryl Base-crc8-alkylcarbonyl 139 20 200932732 base, CrCV alkyl carboxyl group, c6-c1()-arylcarboxy group, crc6-alkylsulfonylthio group, C6-C10-arylhydrosulfanyl group, CrCr alkylsulfonyl group Carbonyl, c3-c8-cycloalkylfluorenylcarbonyl, c6-c1 (rarylcarbonylcarbonyl, crc6-alkylmercaptocarboxy, C6-C1G-aryldecylcarboxy, crc6-alkylsulfonyl-5, C6 -C1()-arylsulfonyl, CrC6-alkyloxythio, C6-C1 (raryloxythio, each of which is optionally substituted one or more times by: CVC6-alkyl ;CrCV alkoxy; c6-c1()-aryloxy; co2h; S03H; CONH2; SO2NH2; CONH2 or so2nh2, wherein the amine functionality is selected from CVC6-alkyl, 〇10 CVQ.-aryl Or C6-C1 (the residue of the r-aryl-Q-C4-alkyl group substituted one or more times, and in the case of an amine group substituted by a di-Ci-Cr alkyl group), the alkyl group The residues may be combined to form a 5 or 6 membered 'ring; an amine group; one or more amine groups substituted with a residue selected from the group consisting of CVC6-alkyl, C6-C10-aryl, C6-C1 ( )-aryl-CVC4-15 alkyl, CVQ-alkylcarbonyl, C6-C1 (r arylcarbonyl, CVCV alkyl base and C6-Ci 〇-aryl base; sulfur nitrogen; ; succinyl; cyano; fluoro; thiol; bromo; iodo; cf3 ® or OCF3; co2h; 20 SO3H; amine; substituted one or more times with a residue selected from the group below Amine group: Ci-CV alkyl group, C6-C10-aryl group, C6-C1()-aryl-Ci-Q-alkyl group, crc6-alkylcarbonyl group, C6-C1()-arylcarbonyl group, CVCV alkane Sulfosyl group 140 200932732 and C6-C10-arylsulfonyl; a disubstituted amine group of the following formula (II): —NW

10 15 ❹ 其中〇代表〇或1，而W代表氧、CH2或NR6，R6係選自氫與CkC^-烷基，及其中化學式(II)中的亞曱基可選擇性地被CkCp烷基、氟代基或氣代基取代一或二次； CONH2 ; so2NH2; conh2或so2nh2，其中該胺基官能度被選自 CVCV烷基、C6-C10-芳基或C6-C1()-芳基-CrQr烷基的殘基取代一或二次，及其中在一種經二-CrCy烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6 員環；硫氫基；羥基；硝基；氰基；氟磺醯基；選自氟代基、氣代基、溴代基或碘代基之鹵素； cf3 ; OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次： 141 20 200932732 CrCV烷基；CVC6-烷氧基；COOH ; S03H ; CONH2 ; S02NH2 ; CONH2或S02NH2，其中該胺基官能度被選自crc6-烷基、c6-c1(r芳基或c6-c1()-芳基 -crc4-烷基的殘基取代一次或多次，及其中在一種經 5 二-Ci-CfT烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：Ci-CV烷基、c6-c10-芳基、c6-c10-芳基-CrC4-烷基、Ci-CV烷基羰基、 C6-C1(r芳基羰基、CVCV烷基磺醯基及c6-c1()-芳基磺〇 10 醯基；硫氫基；羥基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；CF3或OCF3 ; ' 及其中R1至R5中之任二或多者可結合而形成稠合 · 的飽和、不飽和或芳族同環或雜環系統； η代表0或1 ; m代表0、1、2、3、4、5或6 ; 15 X代表氧或硫； Y代表： a) 氫； V b) Ci-Ci8_烧基、早元不飽和或多元不飽和C2_Ci8_ 亞烷基、c3-c8-環烷基、C6-C1(r芳基、CVQ。-芳基10 15 ❹ wherein 〇 represents 〇 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and CkC^-alkyl, and the fluorenyl group in the formula (II) is optionally CkCp alkyl Substituting one or two times with a fluoro or a gas group; CONH2; so2NH2; conh2 or so2nh2, wherein the amine functionality is selected from a CVCV alkyl group, a C6-C10-aryl group or a C6-C1()-aryl group Substituting a residue of a -CrQr alkyl group one or two times, and in the case of an amine functional group substituted with a di-CrCy alkyl group, the alkyl residue may be bonded to form a 5 or 6 membered ring; Hydroxy; nitro; cyano; fluorosulfonyl; halogen selected from fluoro, carbyl, bromo or iodo; cf3; OCF3; or a saturated An unsaturated or aromatic heterocyclic ring system which is optionally substituted one or more times by: 141 20 200932732 CrCV alkyl; CVC6-alkoxy; COOH; S03H; CONH2; S02NH2; CONH2 or S02NH2, Wherein the amine functionality is substituted one or more times by a residue selected from the group consisting of crc6-alkyl, c6-c1 (raryl or c6-c1()-aryl-crc4-alkyl, and Wherein in the case of an amine functionality substituted with 5 di-Ci-CfT alkyl, the alkyl residue may combine to form a 5 or 6 membered ring; an amine group; substituted with a residue selected from the group consisting of One or more amine groups: Ci-CV alkyl, c6-c10-aryl, c6-c10-aryl-CrC4-alkyl, Ci-CV alkylcarbonyl, C6-C1 (rarylcarbonyl, CVCV Alkylsulfonyl and c6-c1()-arylsulfonyl 10 fluorenyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; chloro; bromo; iodo; OCF3; ' and any two or more of R1 to R5 may be combined to form a fused, saturated or unsaturated homocyclic or heterocyclic ring system; η represents 0 or 1; m represents 0, 1, 2 , 3, 4, 5 or 6; 15 X represents oxygen or sulfur; Y represents: a) hydrogen; V b) Ci-Ci8_alkyl, early-unsaturated or polyunsaturated C2_Ci8_alkylene, c3-c8- Cycloalkyl, C6-C1 (r aryl, CVQ.-aryl

20 -CrC8-烷基、CkQ-烷氧基、c6-c1()-芳氧基、c6-c10-芳基-crc8-烷氧基、CVCV烷氧基羰基、c6-c1(r芳氧基羰基、C6-C1()-芳基-CrC8-烷氧基羰基、Ci-CV烷基羰基、 c6-c10-芳基羰基、c6-c10-芳基-crc8-烷基羰基、crc6-烷基羧基、c6-c1()-芳基羧基、crc6-烷基氫硫基、 142 200932732 C^Cio-芳基氫硫基、CVC6-烧基疏基幾基、C3_c8_環^ 基魏基獄基、C6_Ci〇-芳基疏基幾基、CpC^-貌基疏其緩基、C6-C1()-芳基Μ基羧基、CVC6-烧基續醯基、c6_c 方基績醯基、Ci-CV烧基氧硫基、C6-C1(r芳基氧硫美戈一 5 種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其中各者選擇性地被下列各者取代一次或多-欠. blKVCV烷基、C3-C8-環烷基、c6-c1〇_ 芳基、魯 C6-Ci〇-芳基-Ci-Cg-烧基、Ci-C6-烧氧基、C6_C1〇_芳氣基、C6-C1()-芳基-CVCs-烧氧基、Ci-C6-燒氧基幾基、 - C6-C]〇-芳氧基叛基、C6-Ci〇-芳基燒氧基_ 基、Ci_C6_烧基幾基、C6-Ci〇-芳基幾基、C6-C1〇-芳其^ -Ci-C8-烧基幾基、Ci_C6_烧基叛基、C6-C1〇-芳基幾^ 基、Ci-C6-烧基鼠硫基、C6-Ci〇-芳基氮琉基、CpC 烷基巯基羰基、CVC8-環烷基巯基羰基、c6_Ci(r芳基疏基幾基、Ci-CV烧基魏基叛基、CVCiq-芳基疏基竣春基、Ci-C6-烧基續醯基、C6-Ci〇-芳基續酿基、Ci—Cg 烧基氧硫基、C6_Ci〇-芳基氧硫基；其中各者選擇性地被下列各者取代一次或多次：CrC6-烷基；CrC6_ 烷氧基；CONH2、S〇2NH2 ;其中該胺基官能度被 20 crc6-烷基取代一次或二次之conh2或s〇2nh2 ; S〇3H ; C〇2H ;胺基；經選自下列群中的殘基取代— 或多次之胺基.Ci_C6_烧基、C6-Ci〇-芳基、C6-Ci〇-芳基-C!-C6_烧基、Ci_C6_烧基叛基、CVCiq-芳基幾基、 Ci-CV烧基績醯基及CVCiq-芳基續酿基；硫氫基；輕 143 200932732 基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；CF3 ;或 OCF3 ; 其中bl)中的數個取代基可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統；或被： 10 1520-CrC8-alkyl, CkQ-alkoxy, c6-c1()-aryloxy, c6-c10-aryl-crc8-alkoxy, CVCV alkoxycarbonyl, c6-c1 (r aryloxy) Carbonyl, C6-C1()-aryl-CrC8-alkoxycarbonyl, Ci-CV alkylcarbonyl, c6-c10-arylcarbonyl, c6-c10-aryl-crc8-alkylcarbonyl, crc6-alkyl Carboxyl, c6-c1()-arylcarboxyl, crc6-alkylthiol, 142 200932732 C^Cio-arylthiol, CVC6-alkylthiol, C3_c8_cyclopropyl , C6_Ci〇-aryl sulfhydryl group, CpC^- phenotype group, C6-C1()-aryl decylcarboxy group, CVC6-alkyl group, c6_c square base, Ci-CV Alkylthio-, C6-C1 (r-aryloxythiometh) - a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, each of which is optionally replaced by One or more - owed. blKVCV alkyl, C3-C8-cycloalkyl, c6-c1 〇 aryl, 鲁 C6-Ci 〇-aryl-Ci-Cg-alkyl, Ci-C6-alkoxy, C6_C1〇_aryl, C6-C1()-aryl-CVCs-alkoxy, Ci-C6-alkoxy, -C6-C]indole-aryloxy, C6-Ci〇- Aryloxy group _ base, Ci_C6_ burning Alkyl, C6-Ci〇-aryl, C6-C1〇-aryl^^-Ci-C8-alkyl group, Ci_C6_alkyl group, C6-C1〇-aryl group, Ci-C6-alkylsulfanyl, C6-Ci〇-arylazinyl, CpC alkylmercaptocarbonyl, CVC8-cycloalkylfluorenylcarbonyl, c6_Ci (rarylthiol, Ci-CV alkyl) Weiji ruthenium, CVCiq-aryl sulfhydryl fluorenyl, Ci-C6-alkyl thiol, C6-Ci 〇-aryl continuation, Ci-Cg alkyl oxythio, C6_Ci 〇-aryl An oxythio group; each of which is optionally substituted one or more times by: CrC6-alkyl; CrC6_alkoxy; CONH2, S〇2NH2; wherein the amine functionality is replaced by 20 crc6-alkyl Or a second conh2 or s〇2nh2; S〇3H; C〇2H; an amine group; substituted with a residue selected from the group consisting of - or a plurality of amine groups. Ci_C6_alkyl, C6-Ci〇-芳, C6-Ci〇-aryl-C!-C6_alkyl, Ci_C6_alkyl group, CVCiq-aryl group, Ci-CV alkyl group and CVCiq-aryl renewable base; sulfur Hydrogen; light 143 200932732 base; nitro; cyano; fluoro; chloro; bromo; iodo; CF3; or OCF3; Substituents may combine to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; or: 1015

b2)羥基；硫氫基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；cf3 ; co2h ; so3h ; OCF3 ; conh2 ; so2nh2 ; conh2或so2nh2，其中該胺基官能度被選自CrCV烷基、c6-c1(r芳基或c6-c1()-芳基 -CrCV烷基的殘基取代一或二次，及其中在一種經二 -Q-C6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、c6-c10-芳基、CVQ。-芳基-CrCV烷基、CVCV烷基羰基、 c6-c1(r芳基羰基、CVC6-烷基磺醯基及c6-c1()-芳基磺醯基；或具下列化學式（II)之一種經二取代的胺基：B2) hydroxy; sulfhydryl; nitro; cyano; fluoro; chloro; bromo; iodo; cf3; co2h; so3h; OCF3; conh2; so2nh2; conh2 or so2nh2, wherein the amine group The functionality is substituted one or two times with a residue selected from the group consisting of a CrCV alkyl group, a c6-c1 (r aryl group or a c6-c1()-aryl-CrCV alkyl group, and a di-Q-C6-alkane thereof In the case of a substituted amino functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of: crc6-alkane , c6-c10-aryl, CVQ.-aryl-CrCV alkyl, CVCV alkylcarbonyl, c6-c1 (rarylcarbonyl, CVC6-alkylsulfonyl and c6-c1()-arylsulfonate A thiol group; or a disubstituted amino group of the following formula (II):

ί~\ —N W Η7] 0 (II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-C6-烷基，及其中化學式(II)中的亞甲基可選擇性地被G-C6-烷基、氟代基或氯代基取代一或二次；或被： b3) —種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一 144 20 200932732 或多次：CrC6-烷基；CrC6-烷氧基；COOH ; so3h ; conh2;so2nh2 ; CONH2或S02NH2，其中該胺基官能度被選自crc6-烷基、c6-c1(r芳基或c6-c10-芳基-crc4-烷基的殘基取代一次或多次，及其中在一 5 種經二-CrC6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、 c6-c1(r芳基、CVQ。-芳基-OC4-烷基、CVCV烷基羰基、c6-c1()-芳基羰基、crc6-烷基磺醯基及c6-c10-芳 10 基續酿基；硫氫基；經基；确基；氰基；氟代基；氣代基；溴代基；碘代基；CF3或OCF3 ; c)S03H ;胺基；經選自下列群中的殘基取代一或多次之胺基：crc6-烷基、c6-c10-芳基、c6-c10-芳基 -crc8-烷基、crc6-烷基羰基、c6-c1()-芳基羰基、 15 CrCV烷基磺醯基及C6-Cnr芳基磺醯基；CONH2 ; S02NH2 ; CONH2或S02NH2，其中該胺基官能度被選自 CrC6-烷基、C6-C1(r芳基或C6-C1(r芳基-CrC6-烷基的殘基取代一或二次，及其中在一種經二-Q-C6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員 20 環；硫氫基；羥基；硝基；氰基；氟磺醯基；選自氟代基、氣代基、溴代基或碘代基之i素；CF3 ;或〇cf3 ; 前提在於在η代表0及m代表0之情況下： a)R2 或 R4並非代表取代基C(=A)-N(B)-S〇2-NR6R7， 145 200932732 其中A代表氧或硫，B代表氳、氰基、CrC6-烷基、CrC6-烷氧基-烷基、C3-C7-環烷基、C3-C6-烯烴基、C3-C6-炔基或選擇性地經取代的苄基衍生物，及R6與R7係彼此獨立地代表氫或一有機殘基或一起代表一個有機環狀 5 結構； b) 當Y代表未經取代的苯基時，R1至R5係彼此獨立地並非代表氫、氟代基、溴代基、氯代基、碘代基或一烷基游離基； c) R2或R4並非代表一種吡唑-3-基-衍生物；及 10 d)經R1至R5取代的苯基環及Y並非代表下列組合：經R1至R5取代的苯基環 Y 2-氣苯基 4-氣苯基 2,3-二曱基苯基 4-氣苯基 2,4-二乳苯基 4-氣苯基 2-氣-3-甲基苯基 4-氣苯基 2,5-二氟苯基 4-甲基苯基 2-甲氧基-4-氯苯基 4-氣苯基 2-氣苯基 4-甲基苯基 2,6-二氣苯基 4-氣苯基 2-(三氟曱基氫硫基）苯基苯基 2,3,4-三甲基苯基 4-氣苯基 2,5-二氟苯基 4->臭苯基 2,4-二甲基苯基 4-氣苯基 4-氣苯基 4-氣苯基 3-氣苯基 4-氣苯基 4->臭苯基 4-氣苯基 2-氣苯基 4-溴苯基 2,5-二氟苯基 4-氣苯基 4-氣苯基 4->臭苯基 3,5-二甲基苯基 4-氣苯基 200932732 4-三氟曱氧基苯基 4-辛基苯基 4-三氟曱氧基苯基 3-苯氧基苯基 2,3-二氫-2,2-二甲基-7-苯並呋喃基苯基另一前提在於在η代表0及m代表1之情況下，Y並非代表未經取代的苯基，若R1、R2及R5代表氫，R4代表氫、三氟甲氧基、三氟丁氧基、3,3,5,5-四甲基環己氧基、苄氧基、苯氧基、苯基、2-二甲基胺基乙氧基或3-5 曱基苯氧基-甲基，及R3代表氫、三氟甲氧基、三氟丁 0 氧基、3,3,5,5-四甲基環己氧基、苯氧基、4-氣苯氧基、環己基、苯基、嗎啉磺醯基、3,3,5-三甲基環己基 - 胺基磺醯基、2,2,6,6-四曱基哌啶-4-基胺基磺醯基、 2-(二異丙基胺基乙基）胺基磺醯基、4-甲基哌嗪-l-基-10 磺醯基、3,3-二曱基哌啶羰基或3,5-二氯苯氧基、2-二甲基胺基乙氧基或3-甲基苯氧基-曱基；及另一前提在於在m為0及η為0之情況下，Y並非代表Ci_C4_烧基，〇及另一前提在於該化合物並非下列化合物之一： 15 5-苯氧基-3-苯基-(1,3,4)-呋二唑啉-2-酮； 5-十二烷基氧-3-(4-三氟甲氧基-苯基)-3Η-(1,3,4)-呋二唑-2-酮； 5-十六烷基氧-3-(4-三氟甲氧基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 2〇 5-辛基氧-3-(4-三氟甲氧基-苯基)-3Η-(1,3,4)-呋二哇-2-酮； 5-十六烷基氧-3-(3-三氟甲氧基-苯 147 200932732 基)-3Η-(1,3,4)-呋二唑-2-酮； 5-十六烧基氧-3-(4-(4-氣本氧基）-苯基)-3Η-(1,3,4)-呋二唑-2-酮； 5-辛基氧-3-苯基-3H-(1,3,4)-呋二唑-2-酮； 5 5-辛基氧-3-(3-氟-苯基)-3Η-(1,3,4)-呋二唑-2-酮； 5-十六烷基氧-3-(3-氟-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 5-十六烷基氧-3-(3-节氧基-苯基）-3Η-(1,3,4)-呋二唑-2-酮； 5-十六烷基氧-3-苯基-3H-(1，3,4)-呋二唑-2-酮； 10 5-十六烷基氧-3-(4-硝基-苯基）-3Η-(1,3,4)-呋二唑 -2-酮； 5-十六烷基氧-3-(4-甲氧基-苯基）-3Η-(1,3,4)-呋二唾-2-酮； 5-十六烷基氧-3-(4-苄氧基-苯基）-3Η-(1，3,4)-呋二 15 唑-2-酮； 5-癸基氧-3-(4-三氟甲氧基-苯基）-3Η-(1,3,4)-呋二唑-2-酮； 5-十一烷基氧-3-(4-三氟甲氧基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 20 5-十四烷基氧-3-(4-三氟甲氧基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 5-十三烷基氧-3-(4-三氟甲氧基-苯基)-3Η-(1,3,4)-呋二唑-2-酮； 5-(2-(2-己基氧-乙氧基)-乙氧基)-3-(4-三氟曱氧基- 200932732 苯基)-3Η-(1，3,4)-呋二唑-2-酮； 5-((Z)-十八碳-9-烯基氧）-3-(4-三氟甲氧基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 5-(十二烷基氧-乙氧基）-3-(4-三氟甲氧基-苯 5 基)-3Η-(1，3,4)-呋二唑-2-酮； 5-(2-(4-氟苯基）-乙氧基）-3-(4-三氟甲氧基-苯基)-3Η-(1,3,4)-呋二唑-2-酮； 5-((3ss-膽留烷-3-基）-氧）--3-(4-三氟甲氧基-苯 ❹ 基)-3H-(1，3,4)-呋二唑-2-酮； 10 5-(2-丁氧基-乙氧基)-3-(4-三氟甲氧基-苯基)-3H- (1.3.4) -呋二唑-2-酮； ' 5-(7-苯基-庚基氧）-3-(4-三氟曱氧基-苯基）-3H- (1.3.4) -呋二唑-2-酮； 5-(二十二烷基氧-乙氧基）-3-(4-三氟曱氧基-苯 15 基)-3Η-(1，3,4)-呋二唑-2-酮； 5-(2-(1-萘氧基）-乙氧基）-3-(4-三氟甲氧基-苯基)-3Η-(1,3,4)-呋二唑-2-酮； 5-(4-辛基苯氧基）-3-(4-三氟甲氧基-苯基)-3Η-(1,3,4)-呋二唑-2-酮； 2〇 5-(3-苯氧基-苯氧基)-3-(4-三氟甲氧基-苯基)-3H- (1.3.4) -呋二唑-2-酮； 5-(十二烷基氧）-3-(4-三氟曱氧基-苯基)-3Η-(1，3,4)-呋二唑-2-酮； 5-(十二烷基氧)-3-(3,4-二氯-苯基)-311-(1，3,4)-呋二 149 200932732 唑-2-酮； 5-(十二烷基氧)-3-(3，5-二氣-苯基)-3Η-(1,3,4)-呋二唾-2-酮； 5-(十二烷基氧)-3-(3-甲氧基-苯基)-3Η-(1,3,4)-呋二 5 唑-2-酮； 5-(十二烷基氧)-3-(4-甲氧基-苯基)-3Η-(1,3,4)-呋二唾-2-酮；或其一種立體異構物、藥學上可接受的鹽類或酯或前驅藥物。 10 25.如申請專利範圍第24項之化合物，其中R1至R5係彼此獨立地代表：氫；羥基； CrC6-烷基、C6-C10-芳基、Q-CV烷氧基、C6-C10-15 芳氧基、C6-C10-芳基-CrC6-烷氧基、CVCV烷基羧基、 C6-C1()-芳基羧基、CrC6-烷基磺醯基、C6-C1()-芳基磺醯基，其中各者選擇性地被下列各者取代一次或多次： CrC6-烷基、CVCV烷氧基、胺基、crc6-烷基胺基、二-Cl-C6-烧基胺基、經基、氟代基、氣代基、溴代 20 基、氰基、CF3或OCF3 ; 胺基；經選自crc6-烷基、c6-c10-芳基的殘基取代一或多次之胺基； 1-°比D各基、2-°比11 各基或各基，其選擇性地被一 150 200932732 5 或多個選自CVCV烷基、胺基、氟代基、氯代基或cf3 之殘基取代；具下列化學式(II)之一種經二取代的胺基： —N W ° (Π) 其中0代表0或1，而W代表氧、CH2或NR6，R6係選自氫與CrC6-烷基，及其中化學式(II)中的亞甲基可選擇性地被Q-C6-烷基、氟代基或氣代基取代一或二次； ❹ CONH2 ; so2NH2; 10 CONH2或so2nh2，其中該胺基官能度被選自 crc6-烷基或C6-C1Q-芳基的殘基取代一或二次；氟代基；氯代基；溴代基； 15 ❹ cf3 ;或 OCF3。 26. 如申請專利範圍第24或25項之化合物，其中R1至R5中之一或多者代表氳、氣或氯。 27. 如申請專利範圍第26項之化合物，其中R1或R5代表氫或氟。 20 28.如申請專利範圍第24至27項中任一項之化合物，其中R1 至R5中之一或多者代表：羥基；或 crc6-烷氧基、C6-C10-芳氧基、C6-C1(r芳基-CrC6- 151 200932732 烷氧基、crc6-烷基羧基、c6-c1()-芳基羧基、crc6-烷基磺醯基、c6-c1(r芳基磺醯基，其中各者選擇性地被下列各者取代一次或多次：CVC6-烷基、CkCV烷氧基、胺基、Q-C6-烷基胺基、二-crc6-烷基胺基、選擇性地 5 被C i-CV烷基或C6-C 1()-芳基取代一或二次之CONH2或 so2nh2、羥基、氟代基、氯代基、溴代基、氰基、 CF3 或 OCF3。 29. 如申請專利範圍第28項之化合物，其中R2、R3或R4中之一者代表： 10 羥基；或 CVCV烷氧基、C6-C1()-芳氧基或(：6-(：1()-芳基-crc6-烷氧基，其中各者選擇性地被下列各者取代一或多次： CrCV烷基、crc6-烷氧基、胺基、crc6-烷基胺基、二-CrCV烷基胺基、選擇性地被crc6-烷基或c6-c10-芳 15 基取代一或二次之conh2或so2nh2、羥基、氟代基、氯代基或演代基。 30. 如申請專利範圍第24至29項中任一項之化合物，其中R1 至R5中之一或多者代表：胺基； 20~~\ —NW Η7] 0 (II) wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and Q-C 6-alkyl, and the methylene group in the formula (II) a group optionally substituted by a G-C6-alkyl, fluoro or chloro group for one or two times; or by: b3) a saturated, unsaturated or aromatic heterocyclic ring consisting of up to 10 atoms A ring system, which is optionally substituted by 144 20 200932732 or multiple times: CrC6-alkyl; CrC6-alkoxy; COOH; so3h; conh2; so2nh2; CONH2 or S02NH2, wherein the amine functionality is Residues selected from the group consisting of crc6-alkyl, c6-c1 (raryl or c6-c10-aryl-crc4-alkyl substituted one or more times, and substituted in one of five substituted by two-CrC6-alkyl groups In the case of an amino functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of: crc6-alkyl, c6 -c1(r aryl, CVQ.-aryl-OC4-alkyl, CVCV alkylcarbonyl, c6-c1()-arylcarbonyl, crc6-alkylsulfonyl and c6-c10-aryl 10 Sulfhydryl; thiol; thiol; cyano; fluoro; a gas group; a bromo group; an iodo group; CF3 or OCF3; c) S03H; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of crc6-alkyl, c6-c10- Aryl, c6-c10-aryl-crc8-alkyl, crc6-alkylcarbonyl, c6-c1()-arylcarbonyl, 15 CrCV alkylsulfonyl and C6-Cnr arylsulfonyl; CONH2; S02NH2; CONH2 or S02NH2, wherein the amine functionality is one or two times selected from the group consisting of CrC6-alkyl, C6-C1 (r-aryl or C6-C1 (r-aryl-CrC6-alkyl), and Wherein in the case of a di-Q-C6-alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 member 20 ring; a sulfhydryl group; a hydroxyl group; a nitro group; a cyano group; Fluorosulfonyl; an imine selected from the group consisting of fluoro, carbyl, bromo or iodo; CF3; or 〇cf3; provided that η represents 0 and m represents 0: a) R2 or R4 does not represent a substituent C(=A)-N(B)-S〇2-NR6R7, 145 200932732 wherein A represents oxygen or sulfur, and B represents anthracene, cyano, CrC6-alkyl, CrC6-alkoxy-alkane Base, C3-C7-cycloalkyl, C3-C6-alkenyl, C3-C6-alkynyl or selectively substituted benzyl derivative And R6 and R7 independently of each other represent hydrogen or an organic residue or together represent an organic cyclic 5 structure; b) when Y represents an unsubstituted phenyl group, R1 to R5 are independently of each other and do not represent hydrogen, Fluoryl, bromo, chloro, iodo or monoalkyl radical; c) R2 or R4 does not represent a pyrazol-3-yl-derivative; and 10 d) substituted by R1 to R5 The phenyl ring and Y do not represent the following combinations: phenyl ring Y 2-phenylphenyl 4-phenylphenyl 2,3-dimercaptophenyl 4-phenylphenyl 2,4-disaccharide substituted by R1 to R5 Phenyl 4-oxophenyl 2-gas-3-methylphenyl 4-phenylphenyl 2,5-difluorophenyl 4-methylphenyl 2-methoxy-4-chlorophenyl 4- Phenyl 2-phenylphenyl 4-methylphenyl 2,6-diphenylphenyl 4-phenylphenyl 2-(trifluoromethylsulfonyl)phenylphenyl 2,3,4-trimethyl Phenyl 4-phenylphenyl 2,5-difluorophenyl 4-> odor phenyl 2,4-dimethylphenyl 4-phenylphenyl 4-phenylphenyl 4-phenylphenyl 3- benzene 4-Phenylphenyl 4->odor phenyl 4-phenylphenyl 2-phenylphenyl 4-bromophenyl 2,5-difluorophenyl 4-phenylphenyl 4-phenylphenyl 4-> Odor phenyl 3,5-dimethylphenyl 4- Phenyl 200932732 4-trifluorodecyloxyphenyl 4-octylphenyl 4-trifluoromethoxyphenyl 3-phenoxyphenyl 2,3-dihydro-2,2-dimethyl-7 - benzofuranylphenyl is another premise that in the case where η represents 0 and m represents 1, Y does not represent an unsubstituted phenyl group, and if R1, R2 and R5 represent hydrogen, R4 represents hydrogen, trifluoromethoxy , trifluorobutoxy, 3,3,5,5-tetramethylcyclohexyloxy, benzyloxy, phenoxy, phenyl, 2-dimethylaminoethoxy or 3-5 曱Phenoxy-methyl, and R3 represents hydrogen, trifluoromethoxy, trifluorobutoxy, 3,3,5,5-tetramethylcyclohexyloxy, phenoxy, 4-oxobenzene Oxyl, cyclohexyl, phenyl, morpholinsulfonyl, 3,3,5-trimethylcyclohexyl-aminosulfonyl, 2,2,6,6-tetradecylpiperidin-4-yl Aminosulfonyl, 2-(diisopropylaminoethyl)aminosulfonyl, 4-methylpiperazine-l-yl-10sulfonyl, 3,3-dimercaptopiperidinylcarbonyl Or 3,5-dichlorophenoxy, 2-dimethylaminoethoxy or 3-methylphenoxy-indenyl; and another premise is that in the case where m is 0 and η is 0, Y does not represent Ci_C4_ burning base, and another before Insofar as the compound is not one of the following compounds: 15 5-phenoxy-3-phenyl-(1,3,4)-furadiazolin-2-one; 5-dodecyloxy-3-(4) -trifluoromethoxy-phenyl)-3Η-(1,3,4)-furadiazol-2-one; 5-hexadecyloxy-3-(4-trifluoromethoxy-phenyl -3Η-(1,3,4)-furadiazol-2-one; 2〇5-octyloxy-3-(4-trifluoromethoxy-phenyl)-3Η-(1,3, 4)-furovaw-2-one; 5-hexadecyloxy-3-(3-trifluoromethoxy-benzene 147 200932732 base)-3Η-(1,3,4)-furadiazole- 2-keto; 5-hexadecyloxy-3-(4-(4-carbenyloxy)-phenyl)-3Η-(1,3,4)-furadiazole-2-one; 5- Octyloxy-3-phenyl-3H-(1,3,4)-furadiazol-2-one; 5 5-octyloxy-3-(3-fluoro-phenyl)-3Η-(1, 3,4)-furadiazol-2-one; 5-hexadecyloxy-3-(3-fluoro-phenyl)-3indole-(1,3,4)-furadiazol-2-one; 5-hexadecyloxy-3-(3-hydroxy-phenyl)-3Η-(1,3,4)-furadiazol-2-one; 5-hexadecyloxy-3-benzene 3-H-(1,3,4)-furadiazol-2-one; 10 5-hexadecyloxy-3-(4-nitro-phenyl)-3Η-(1,3,4) -furadiazol-2-one; 5-hexadecyloxy-3-(4-methoxy-phenyl)-3indole-(1,3,4)-furodis-2-one; 5-hexadecyloxy-3-(4-benzyloxy-phenyl)-3indole-(1,3,4)-furodi-15oxazol-2-one; 5-mercaptooxy-3-(4) -trifluoromethoxy-phenyl)-3Η-(1,3,4)-furadiazol-2-one; 5-undecyloxy-3-(4-trifluoromethoxy-phenyl -3Η-(1,3,4)-furadiazol-2-one; 20 5-tetradecyloxy-3-(4-trifluoromethoxy-phenyl)-3Η-(1,3 , 4)-furadiazol-2-one; 5-tridecyloxy-3-(4-trifluoromethoxy-phenyl)-3Η-(1,3,4)-furadiazole-2 -ketone; 5-(2-(2-hexyloxy-ethoxy)-ethoxy)-3-(4-trifluorodecyloxy- 200932732 phenyl)-3Η-(1,3,4)- Furadiazol-2-one; 5-((Z)-octadeca-9-enyloxy)-3-(4-trifluoromethoxy-phenyl)-3Η-(1,3,4) -furadiazol-2-one; 5-(dodecyloxy-ethoxy)-3-(4-trifluoromethoxy-phenyl-5yl)-3Η-(1,3,4)-fur Dioxazol-2-one; 5-(2-(4-fluorophenyl)-ethoxy)-3-(4-trifluoromethoxy-phenyl)-3Η-(1,3,4)- Furadiazol-2-one; 5-((3ss-choline-3-yl)-oxo)--3-(4-trifluoromethoxy-phenylhydrazinyl)-3H-(1,3, 4)-furadiazol-2-one; 10 5-(2-butoxy-ethoxy)-3-(4-trifluoromethoxy-phenyl)-3H- (1.3.4)-fur Diazol-2-one ' 5-(7-Phenyl-heptyloxy)-3-(4-trifluorodecyloxy-phenyl)-3H-(1.3.4)-furadiazol-2-one; 5-(II Dodecyloxy-ethoxy)-3-(4-trifluorodecyloxy-phenyl-15-yl)-3indole-(1,3,4)-furadiazol-2-one; 5-(2- (1-naphthyloxy)-ethoxy)-3-(4-trifluoromethoxy-phenyl)-3indole-(1,3,4)-furadiazol-2-one; 5-(4 -octylphenoxy)-3-(4-trifluoromethoxy-phenyl)-3indole-(1,3,4)-furadiazol-2-one; 2〇5-(3-phenoxy -Phenoxy)-3-(4-trifluoromethoxy-phenyl)-3H-(1.3.4)-furadiazol-2-one; 5-(dodecyloxy)-3- (4-Trifluoromethoxy-phenyl)-3Η-(1,3,4)-furadiazol-2-one; 5-(dodecyloxy)-3-(3,4-dichloro -phenyl)-311-(1,3,4)-furo 149 200932732 oxazol-2-one; 5-(dodecyloxy)-3-(3,5-di-phenyl)-3Η -(1,3,4)-furodis-2-one; 5-(dodecyloxy)-3-(3-methoxy-phenyl)-3Η-(1,3,4)- Furodi-5oxazol-2-one; 5-(dodecyloxy)-3-(4-methoxy-phenyl)-3indole-(1,3,4)-furodis-2-one; Or a stereoisomer thereof, a pharmaceutically acceptable salt or ester or a prodrug. 10 25. The compound of claim 24, wherein R1 to R5 are independently of each other: hydrogen; hydroxy; CrC6-alkyl, C6-C10-aryl, Q-CV alkoxy, C6-C10- 15 aryloxy, C6-C10-aryl-CrC6-alkoxy, CVCV alkylcarboxy, C6-C1()-arylcarboxy, CrC6-alkylsulfonyl, C6-C1()-arylsulfonate A thiol group, each of which is optionally substituted one or more times by: CrC6-alkyl, CVCV alkoxy, amine, crc6-alkylamino, bis-Cl-C6-alkylamino, Base group, fluoro group, gas group, bromo 20 group, cyano group, CF3 or OCF3; amine group; amine substituted one or more times by a residue selected from a crc6-alkyl group, a c6-c10-aryl group a group of 1-° ratio D, a ratio of 2-° to 11 or a group, optionally selected from a 150 200932732 5 or a plurality selected from CVCV alkyl, amine, fluoro, chloro or Substituted by a residue of cf3; a disubstituted amino group of the following formula (II): -NW ° (Π) wherein 0 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and CrC 6 - an alkyl group, and the methylene group in the formula (II) thereof may be selectively Q-C6- Substituting one or two groups with a fluoro, or fluoro group; ❹ CONH2 ; so2NH2; 10 CONH2 or so2nh2, wherein the amino functionality is replaced by a residue selected from the group consisting of crc6-alkyl or C6-C1Q-aryl Or twice; fluoro; chloro; bromo; 15 ❹ cf3 ; or OCF3. 26. The compound of claim 24 or 25, wherein one or more of R1 to R5 represents hydrazine, gas or chlorine. 27. The compound of claim 26, wherein R1 or R5 represents hydrogen or fluorine. The compound according to any one of claims 24 to 27, wherein one or more of R1 to R5 represents: a hydroxyl group; or a crc6-alkoxy group, a C6-C10-aryloxy group, a C6- C1(raryl-CrC6- 151 200932732 alkoxy, crc6-alkylcarboxy, c6-c1()-arylcarboxy, crc6-alkylsulfonyl, c6-c1 (rarylsulfonyl), wherein Each is optionally substituted one or more times by: CVC6-alkyl, CkCV alkoxy, amine, Q-C6-alkylamino, di-crc6-alkylamino, optionally 5 29. One or two times of CONH2 or so2nh2, hydroxy, fluoro, chloro, bromo, cyano, CF3 or OCF3 substituted by C i-CV alkyl or C6-C 1()-aryl. A compound according to claim 28, wherein one of R2, R3 or R4 represents: 10 hydroxy; or CVCV alkoxy, C6-C1()-aryloxy or (:6-(:1()) An aryl-crc6-alkoxy group, each of which is optionally substituted one or more times by: CrCV alkyl, crc6-alkoxy, amine, crc6-alkylamino, di-CrCv alkane An amino group, optionally substituted by a crc6-alkyl or a c6-c10-aryl15 group, one or two times c The compound of any one of the claims 25 to 29, wherein one or more of R1 to R5 represents: an amine group, or a hydroxy group, a fluoro group, a chloro group, or a thiol group. ; 20

經選自CVC6-烷基、c6-c10-芳基的殘基取代一或多次之胺基；或具下列化學式（II)之一種經二取代的胺基：An amine group substituted one or more times with a residue selected from a CVC 6-alkyl group, a c6-c10-aryl group; or a disubstituted amino group having the following formula (II):

152 (II) ^]0 200932732 其中0代表〇或1，而W代表氧、CH2或NR6，R6係選自氫與Q-C6-烷基，及其中化學式(II)中的亞曱基可選擇性地被Q-C6-烷基、氟代基或氣代基取代一或二次。 31.如申請專利範圍第30項之化合物，其中R2、R3或R4中之一者代表：胺基；經選自CrC6-烷基、C6-C10-芳基的殘基取代一或多次之胺基；或152 (II) ^]0 200932732 where 0 represents 〇 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and Q-C 6 -alkyl, and the fluorenyl group in formula (II) It is substituted one or two times with a Q-C6-alkyl group, a fluoro group or a gas group. 31. The compound of claim 30, wherein one of R2, R3 or R4 represents: an amine group; one or more times substituted with a residue selected from the group consisting of CrC6-alkyl, C6-C10-aryl Amine; or

10 具下列化學式(II)之一種經二取代的胺基： —N W ° (II) 其中0代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-CV烷基，及其中化學式(II)中的亞甲基可選擇性地被CrC6-烷基、氟代基或氣代基取代一或二次。 32.如申請專利範圍第24至31項中任一項之化合物，其中η 15 代表0 ; m代表0、1、2、3、4、5或6 ;及Υ代表C3-C6- 環烷基或C6-C1(r芳基，其中各者選擇性地被下列各者取代一或多次： ajQ-CV烷基、C6-C10-芳基、C6-C1()-芳基-Q-Cr烷基、Ci_C6-烧氧基、C6-Ci〇-芳氧基、C6_Ci〇-芳基-C1-C4-20 烷氧基，其中各者選擇性地被下列各者取代一次或多次： CrC6-烷基；CVC6-烷氧基；COOH ; CONH2 ; S02NH2 ;被(^-(：6-烷基或c6-c1()-芳基取代一或二次之 153 200932732 conh2或so2nh2 ; S03H ;胺基；經選自下列群中的殘基取代一或多次之胺基：Q-C6-烷基、c6-c10-芳基、 C6-C1()-芳基-CrCr烷基、Q-CV烷基羰基、C6-C1()-芳基羰基、Q-C6-烷基磺醯基及c6-c1()-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；CF3或OCF3 ; 或被： 10 1510 A disubstituted amino group of the following formula (II): —NW ° (II) wherein 0 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and Q-CV alkyl, And the methylene group in the formula (II) thereof may be optionally substituted one or two times with a CrC6-alkyl group, a fluoro group or a gas group. The compound according to any one of claims 24 to 31, wherein η 15 represents 0; m represents 0, 1, 2, 3, 4, 5 or 6; and Υ represents C3-C6-cycloalkyl Or C6-C1 (raryl, each of which is optionally substituted one or more times by: ajQ-CV alkyl, C6-C10-aryl, C6-C1()-aryl-Q-Cr Alkyl, Ci_C6-alkoxy, C6-Ci〇-aryloxy, C6_Ci〇-aryl-C1-C4-20 alkoxy, each of which is optionally substituted one or more times by: CrC6 -alkyl; CVC6-alkoxy; COOH; CONH2; S02NH2; substituted by one or two times (^-(:6-alkyl or c6-c1()-aryl) 200932732 conh2 or so2nh2; S03H; amine One or more amine groups substituted with a residue selected from the group consisting of Q-C6-alkyl, c6-c10-aryl, C6-C1()-aryl-CrCr alkyl, Q-CV Alkylcarbonyl, C6-C1()-arylcarbonyl, Q-C6-alkylsulfonyl and c6-c1()-arylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro Base; gas group; bromo group; iodo group; CF3 or OCF3; or by: 10 15

b)羥基；硫氫基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；cf3 ; ocf3 ; co2h ; so3h ; conh2 ; so2nh2 ; conh2或so2nh2，其中該胺基官能度被選自CkCV烷基、c6-c1()-芳基或c6-c1(r芳基 -CrCr烷基的殘基取代一次或多次，及其中在一種經二 -CrC6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；被心/^烷基或苯基取代一或多次之胺基；具下列化學式（II)之一種經二取代的胺基：b) hydroxy; sulfhydryl; nitro; cyano; fluoro; chloro; bromo; iodo; cf3; ocf3; co2h; so3h; conh2; so2nh2; conh2 or so2nh2, wherein the amine group The functionality is substituted one or more times by a residue selected from a CkCV alkyl group, a c6-c1()-aryl group or a c6-c1 (raryl-CrCr alkyl group, and wherein it is substituted with a di-CrC6-alkyl group In the case of an amine functional group, the alkyl residue may be bonded to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times by a heart/alkyl group or a phenyl group; having the following chemical formula (II) a disubstituted amino group:

其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-C4-烷基，及其中化學式(II)中的亞曱基可選擇性地被Q-C4-烷基、氟代基或氣代基取代一或二次；或被： c)一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次： 154 20 200932732 CrC6-烷基；Q-CV烷氧基；c〇OH ; CONH2 ; S〇2NH2 ;被CVCV烧基或CVCht芳基取代一或二次之 CONH2或S02NH2 ; SO3H ;胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6-烷基、c6-C10-芳基、 5 C6-Ci〇-芳基-Ci-C4-烷基、CVCV烷基羰基、C6-Cicr芳基羰基、CVCV炫基磺醯基及C6-C1(r芳基磺酿基；硫氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；cf3或ocf3。 33.如申請專利範圍第32項之化合物，其中n代表〇 ; m代表0 10 或1 ;及Y代表一個苯基、1-萘基、2-萘基、2-吡啶基、 3- »比啶基或4-»比啶基環系統。 • 34·如申請專利範圍第33項之化合物，其中γ被下列各者取代一或多次：CkCV烷基；苯基；q-CV烷氧基；羥基；氟代基；氯代基；溴代基；cf3 ; ocf3 ;胺基；或 15 選擇性地被CrC6·烷基取代一或二次之c〇NH2或 S〇2NH2，其中該等選擇性的crC6-烷基殘基可結合而形成5或6員環。 35. 如申請專利範圍第34項之化合物，其中m代表〇,及γ代表被羥基、氟代基、氯代基或溴代基取代一或二次之苯 20 基。 36. 如申請專利範圍第34項之化合物，其中m代表0 ;及Y代表本基，其在4-位置被氣代基或被氣代基取代、在2-與 4- 位置被氟代基取代、在2-與4-位置被氣代基取代或在 4-位置被苯基取代。 155 200932732 37.如申請專利範圍第24項之化合物，其中爪為〇 ; η為〇 ; γ 代表被鼠代基、氣代基或漠代基取代一或二次之苯基；及R2至R4中之任一者代表〇R7，其中R7係選自氫與 Ci_C6_ 燒基。 5 38.如申凊專利範圍第37項之化合物，其中γ代表苯基，其在4-位置被氟代基或被氯代基取代、在2與4位置被氟代基取代或在2-與4-位置被氣代基取代。 39.如申請專利範圍第37或38項之化合物，其中r1*r5代表氫或氟。 1〇 40.如申請專利範圍第37至39項中任一項之化合物，其中R2 或R3與R4代表羥基。 41. 一種具化學式(I)的化合物：Wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and Q-C 4 -alkyl, and the fluorenyl group in the formula (II) is optionally Q-C 4 -alkane a fluoro, fluoro or ke group substituted one or two times; or by: c) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, optionally substituted by One or more times: 154 20 200932732 CrC6-alkyl; Q-CV alkoxy; c〇OH; CONH2; S〇2NH2; CONH2 or S02NH2 substituted by CVCV or CVCht aryl; Amine; one or more amine groups substituted with a residue selected from the group consisting of CrC6-alkyl, c6-C10-aryl, 5 C6-Ci〇-aryl-Ci-C4-alkyl, CVCV Alkylcarbonyl, C6-Cicr arylcarbonyl, CVCV sulfonylsulfonyl and C6-C1 (rarylsulfonic acid; sulfhydryl; hydroxy; nitro; cyano; fluoro; gas; bromine a thiol group; cf3 or ocf3. 33. A compound according to claim 32, wherein n represents hydrazine; m represents 0 10 or 1; and Y represents a phenyl group, 1-naphthyl group, 2-naphthalene Base, 2-pyridyl, 3-»pyridinyl or 4-»pyridinyl The ring system. 34. The compound of claim 33, wherein γ is substituted one or more times by: CkCV alkyl; phenyl; q-CV alkoxy; hydroxy; fluoro; chloro a bromo group; cf3; ocf3; an amine group; or 15 optionally substituted by CrC6.alkyl, one or two times, c〇NH2 or S〇2NH2, wherein the selective crC6-alkyl residue is Combining to form a 5 or 6 membered ring. 35. A compound of claim 34, wherein m represents hydrazine, and γ represents benzene substituted by a hydroxy, fluoro, chloro or bromo group. The base of claim 34, wherein m represents 0; and Y represents the base, which is substituted at the 4-position by a gas group or by a gas group, at the 2- and 4- positions. a fluoro group substituted, substituted by a gas group at the 2- and 4-positions or substituted with a phenyl group at the 4-position. 155 200932732 37. The compound of claim 24, wherein the claw is ruthenium; η is ruthenium; γ represents a phenyl group substituted one or two times by a murine base, a gas group or a moiety group; and any one of R2 to R4 represents 〇R7, wherein R7 is selected Hydrogen and Ci_C6_alkyl. 5 38. A compound according to claim 37, wherein γ represents a phenyl group which is substituted at the 4-position with a fluoro group or by a chloro group, and is fluorinated at positions 2 and 4. The base is substituted or substituted with a gas group at the 2- and 4-positions. 39. A compound according to claim 37 or 38, wherein r1*r5 represents hydrogen or fluorine. The compound according to any one of claims 37 to 39, wherein R2 or R3 and R4 represent a hydroxyl group. 41. A compound of formula (I):

R1至R5係彼此獨立地代表：氫； ocv烧基、C3_C8_環燒基、c6_Ci。芳基、c6_Ci〇· 芳基-crc8-烧基、CKV烷氧基、c6_Ci〇_芳氧基、 20 C6_Cl0_芳基-Cl—C8·貌氧基、CrC6-院氧基幾基、C6-Cl0_ 芳氧基叛基、C6<V芳基-cvc8-炫氧基錄、CVCV燒基羰基、c6-c10-芳基羰基、C6_Ci〇_芳基々々烷基羰 156 200932732 5 Ο 10 15 ❹ 20 基、CVC6-烷基羧基、C6-C1(r芳基羧基、CrQ-烷基氫硫基、C6-Ci〇-方基鼠硫基、C!-C6-烧基疏基援基、 c3-c8-環烷基毓基羰基、c6-c1(r芳基酼基羰基、crc6-烷基Μ基羧基、C6-C1Q-芳基锍基羧基、CrC6-烷基磺醯基、c6-c1()-芳基磺醯基、crc6-烷基氧硫基、c6-c1()-芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次： CkCV烷基；crc6-烷氧基；c6-c1()-芳氧基； C02H ； SO3H ； CONH2 ； SO2NH2 ； CONH2 或 so2nh2，其中該胺基官能度被選自crc6-烷基' c6-c10-芳基或C6-C10-芳基-CVC4-烷基的殘基取代一次或多次，及其中在一種經二-CrCV烷基取代的胺基官能度之情況下、該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6-烷基、C6-C1(r芳基、C6-C10-芳基-CVC4-烷基、CkCV烷基羰基、C6-C1()-芳基羰基、CrCer烷基績酿基及C6-C 1 〇-方基續酿基，硫氮基；輕基；石肖基；氰基；氟代基；氯代基；溴代基；碘代基；cf3 或 ocf3 ; co2h ; so3H ; 胺基；經選自下列群中的殘基取代一或多次之胺基： CrC6-烷基、C6-C10-芳基、C6-C10-芳基-CVC6-烷基、 crc6-烷基羰基、C6-C1()-芳基羰基、CVCV烷基磺醯基 157 200932732 及C6-C1()-芳基續醯基；具下列化學式(II)之一種經二取代的胺基： Γ~\ —N WR1 to R5 are independently of each other: hydrogen; ocv alkyl, C3_C8_cycloalkyl, c6_Ci. Aryl, c6_Ci〇·aryl-crc8-alkyl, CKV alkoxy, c6_Ci〇_aryloxy, 20 C6_Cl0_aryl-Cl-C8·morphoxy, CrC6-homoyloxy, C6- Cl0_ aryloxy group, C6<Varyl-cvc8-decyloxy, CVCV alkylcarbonyl, c6-c10-arylcarbonyl, C6_Ci〇_aryldecylcarbonyl 156 200932732 5 Ο 10 15 ❹ 20 base, CVC 6-alkyl carboxyl group, C6-C1 (r aryl carboxyl group, CrQ-alkyl thiol group, C6-Ci 〇-aryl thiol group, C!-C6-alkyl group, c3 -c8-cycloalkylcarbonylcarbonyl, c6-c1 (rarylcarbonylcarbonyl, crc6-alkylindenylcarboxy, C6-C1Q-aryldecylcarboxy, CrC6-alkylsulfonyl, c6-c1 ()-Arylsulfonyl, crc6-alkyloxythio, c6-c1()-aryloxythio, each of which is optionally substituted one or more times by: CkCV alkyl; crc6 - alkoxy; c6-c1()-aryloxy; C02H; SO3H; CONH2; SO2NH2; CONH2 or so2nh2, wherein the amine functionality is selected from the group consisting of crc6-alkyl 'c6-c10-aryl or C6- Residue of a C10-aryl-CVC4-alkyl group substituted one or more times, and an amine function substituted with a di-CrCV alkyl group In the case of a degree, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of CrC6-alkyl, C6-C1 ( Raryl, C6-C10-aryl-CVC4-alkyl, CkCV alkylcarbonyl, C6-C1()-arylcarbonyl, CrCer alkyl, and C6-C 1 〇-aryl aryl, Sulfuryl; light base; schiffki; cyano; fluoro; chloro; bromo; iodo; cf3 or ocf3; co2h; so3H; amine; substituted by a residue selected from the group below Or multiple amino groups: CrC6-alkyl, C6-C10-aryl, C6-C10-aryl-CVC6-alkyl, crc6-alkylcarbonyl, C6-C1()-arylcarbonyl, CVCV alkyl Sulfosyl group 157 200932732 and C6-C1()-aryl thiol group; a disubstituted amine group of the following formula (II): Γ~\ -NW

其中〇代表0或1，而w代表氧、CH2或NR6，R6係選自氫與Q-CV烷基，及其中化學式(π)中的亞甲基可選擇性地被Q-CV烷基、氟代基或氯代基取代一或二次； CONH2 ; so2NH2; 10 15Wherein 〇 represents 0 or 1, and w represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and Q-CV alkyl, and the methylene group in the chemical formula (π) thereof is optionally Q-CV alkyl, One or two substitutions of a fluoro or chloro group; CONH2; so2NH2; 10 15

conh2或so2nh2,其中該胺基官能度被選自crc6-烧基、C6-C1Q-方基或C6-Ci〇-^基-C1-C6-烧基的殘基取代一或二次，及其中在一種經二-CrC6-烷基取代的胺基官能度之情況下、該烷基殘基可結合而形成5或6員環；硫氫基；羥基；硕基；Conh2 or so2nh2, wherein the amino functionality is substituted one or two times with a residue selected from the group consisting of a crc6-alkyl group, a C6-C1Q-aryl group or a C6-Ci〇-yl-C1-C6-alkyl group, and In the case of a di-CrC6-alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; a sulfhydryl group; a hydroxyl group;

氰基；氟確醜基；選自氟代基、氣代基、溴代基或蛾代基之自素； CF3 ; OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次： Ci-CV：^ 基；Ci-C6_院氧基；C〇〇H ; so3h · 158 20 200932732 CONH2 ; S02NH2 ; CONH2或so2nh2，其中該胺基官能度被選自Crc6-烷基、C6-C1()-芳基或C6-C1(r芳基 -CVC4-烷基的殘基取代一次或多次，及其中在一種經二烷基取代的胺基官能度之情況下，該烷基殘 5 基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6-烷基、C6-C10-芳基、C6-C1(r芳基-OC4-烷基、crc6-烷基羰基、 c6-c1()-芳基羰基、crc6-烷基磺醯基及c6-c1(r芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代 10 基；溴代基；碘代基；CF3或OCF3 ; 及其中R1至R5中之任二或多者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統； η代表0 ; m代表0 ; Y代表選擇性地被下列各者取代一或多次之苯基： 15 a)C!-C6-烧基、C6-Ci〇-方基、C6-C!。-芳基-Ci_C8_烧基、CrCV烷氧基、C6-C10-芳氧基、C6-C1(r芳基-CVC8-烷氧基、CrCV烷氧基羰基、C6-C1(r芳氧基羰基、 C6_Ci〇- ^•基-Ci_C8-烧乳基幾基、Ci_C6_烧基祿基、 c6-c1(r芳基羰基、c6-c1()-芳基-crc8-烷基羰基、crc6-20 烧基叛基、C6-Ci〇-芳基叛基、C1-C6-烧基氮硫基、 c6-c1()-芳基氫硫基、Q-CV烷基巯基羰基、c3-c8-環烷基Μ基羰基、C6-C1Q-芳基巯基羰基、CVC6-烷基酼基羧基、C6-C1()-芳基酼基羧基、CkQ-烷基磺醯基、c6-c10-芳基磺醯基、crc6-烷基氧硫基、c6-c1()-芳基氧硫基； 159 200932732 其中各者選擇性地被下列各者取代一或多次： Cj-CV烷基；crc6-烷氧基；選擇性地被crc6-烷基取代一或二次之conh2或so2nh2 ; so3h ; co2h ; 胺基；經選自下列群中的殘基取代一或多次之胺 5 基：CrCV烷基、C6-C10-芳基、C6-C10-芳基-CVC4-烷基、Ci-C6-烧基幾基、C6-Ci〇-^基獄基、Ci_C6-烧基磺醯基及C6-C1()-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；cf3 或 ocf3 ; 10 其中該等選擇性取代基中之數者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統；或 b)—種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次：OC6-烷基；CkCV烷氧基；COOH ;選擇性地被 15 CVC6-烷基取代一或二次之conh2或so2nh2 ; so3h ; 胺基；經選自下列群中的殘基取代一或多次之胺基： Ci_C6_ 烧基、C6-Ci〇-芳基、C6_Ci〇-芳基-C1-C4-烧基、 CrCV烷基羰基、C6-C1()-芳基羰基、（VCV烷基磺醯基及(:6-(:1()-芳基磺醯基；硫氫基；羥基；硝基；氰基； 20 氟代基；氯代基；溴代基；碘代基；CF3或OCF3 ;或 C)羥基；硫氫基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；cf3 ; ocf3 ; co2h ; S03H ; conh2 ; so2nh2 ; conh2或so2nh2，其中該胺基官能度被選IQ-Ce-烷基、C6-C1(r芳基或C6-C1()-芳基-CrC4- 200932732 5 烷基的殘基取代一次或多次’及其中在一種經二-Crc6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6-烷基、C6-C1(r芳基、C6-C10-芳基 -CrC8-烷基、CrC6-烷基羰基、C6-C1(r芳基羰基、 CVC6-烷基磺醯基及c6-c1(r芳基磺醯基；具下列化學式 (IV)之一種經二取代的胺基： /~\ ❹ W ° (IV) 其中〇代表0或1 ’而W代表氧、CH2或NR6，R6係選 10 自氫與CrCV烷基，及其中化學式(1\^中的亞甲基可選擇性地被(^-(：4-烷基、氟代基或氯代基取代一或二次；或其一種立體異構物、藥學上可接受的鹽類或酯或前驅藥物；月1J提在於： 15 ❹ a)R2或R4並非代表取代基c(=A)_N(B)_s〇2_NR6R7，其中A代表氧或硫，B代表氫、氰基、Ci_c6_烷基、Ci_C6_ 烧氧基-烧基、c3-c7-環燒基、C3_C6_稀烴基、C3_c6_快基或選擇性地經取代的节基衍生物，及R6與r7係彼此 20 獨立地代表氫或一有機殘基或一起代表一個有機環狀結構； b)田Y代表未經取代的苯基時，“至尺5係彼此獨立地並非代表氫、_基1代基、氯代基、魏基或-烧基游離基； 161 200932732 c) R2或R4並非代表一種吡唑-3-基-衍生物；及 d) 經取代R1至R5的苯基環及Y並非代表下列組合：經R1至R5取代的苯基環 Y 2-氣苯基 4-氣苯基 2,3-二曱基苯基 4-氣苯基 2,4-二氣苯基 4-氣苯基 2-氯-3-甲基苯基 4-氣苯基 2,5-二氟苯基 4-甲基苯基 2-甲氧基-4-氣笨基 4-氣苯基 2-氣苯基 4-曱基苯基 2,6-二氣苯基 4-氣苯基 2-(三氟甲基氫硫基）苯基苯基 2,3,4-三甲基苯基 4-氣苯基 2,5-二氟苯基 4->臭苯基 2,4-二甲基苯基 4-氣苯基 4-氣苯基 4-氣苯基 3-氣苯基 4-氣苯基 4-溴苯基 4-氣苯基 2-氣苯基 4-溴苯基 2,5-二氟苯基 4-氣苯基 4-氣苯基 4-溴苯基 3,5-二甲基苯基 4-氣苯基 4-三氟甲氧基苯基 4-辛基苯基 4-三氟曱氧基苯基 3-苯氧基苯基 2,3-二氫-2,2-二甲基-7-苯並呋喃基苯基 42.如申請專利範圍第41項之化合物，其中R1至R5係彼此獨 5 立地代表：氫；羥基； 200932732 5 Ci-C6-烧基、C6-Ci〇-方基、Ci_C6-烧氣基、C6-Ci〇-芳氧基、C6-C10-芳基-CrC6-烷氧基、Q-Q-烷基羧基、 C6_Ci〇-^基叛基、Ci_C6_烧基績酿基、C6-Ci〇-芳基績酿基，其中各者選擇性地被下列各者取代一次或多次： Ci_C6_烧基、Ci_C6-院氧基、胺基、Ci-Cg-炫基胺基、二-Ci_C6-烧基胺基、輕基、氣代基、氣代基、漠代基、氰基、CF3或OCF3 ; 胺基； ❹ 經選自crc6-烷基、c6-c10-芳基的殘基取代一或多 10 次之胺基； 1-吡咯基、2-吡咯基或3-吡咯基，其選擇性地被一或多個選自之殘基取RQ-Qr烷基、胺基、氟代基、氯代基或CF3 ; 具下列化學式(II)之一種經二取代的胺基： 15 ❿ —N W ° (II) 其中〇代表〇或1，而W代表氧、CH2或NR6，R6係選自氫與CrC6-烷基，及其中化學式(II)中的亞甲基可選擇性地被CrCV烷基、氟代基或氯代基取代一或二次； conh2 ； 20 so2nh2 ； CONH2或S02NH2，其中該胺基官能度被選自crc6-烷基或c6-c1(r芳基的殘基取代一或二次；銳代基； 163 200932732 氣代基；溴代基； cf3 ;或 OCF3。 5 43.如申請專利範圍第41或42項之化合物，其中R1或R5中之一或多者代表氫、氣或氯。 44. 如申請專利範圍第43項之化合物，其中R1或R5代表氫或氟。 45. 如申請專利範圍第41至44項中任一項之化合物，其中R1 10 或R5中之一或多者代表：經基；或 Ci-C6-烧氧基、C6-Ci〇-芳氧基、C6-Ci〇-芳基-Ci_C6-烷氧基、CVC6-烷基羧基、C6-C1()-芳基羧基、CVCV烷基磺醯基、c6-c1()-芳基磺醯基，其中各者選擇性地被下 15 列各者取代一次或多次：CVCV烷基、CVCV烷氧基、胺基、CVC6-烷基胺基、二-CVCV烷基胺基、選擇性地被CrC6-烷基或C6-C1()-芳基取代一或二次之CONH2或 S02NH2、羥基、氟代基、氣代基、溴代基、氰基、 CF3 或 OCF3。 20 46.如申請專利範圍第45項之化合物，其中R2、R3或R4中之一者代表羥基；或 crc6-烷氧基、C6-C10-芳氧基或c6-c10-芳基-crc6-烷氧基，其中各者選擇性地被下列各者取代一或多次： CrC6-烷基、CrC6-烷氧基、胺基、CVCV烷基胺基、 200932732 5 二-CrC6-烷基胺基、選擇性地被CVC6-烷基或c6-c10-芳基取代一或二次之conh2或so2nh2、羥基、氟代基、氣代基或溴代基。 47.如申請專利範圍第41至46項中任一項之化合物，其中R1 至R5中之一或多者代表胺基；經選自CrC6-烷基、C6-C10-芳基的殘基取代一或多次之胺基；或 Ο 具下列化學式(II)之一種經二取代的胺基： !~\ —N W H7] °(11) 羲 10 其中0代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-CV烷基，及其中化學式(II)中的亞甲基可選擇性地被Q-CV烷基、氟代基或氣代基取代一或二次。 48.如申請專利範圍第47項之化合物，其中R2、R3或R4中之一者代表胺基； 15 ❹ 被選自CrC6-烷基、C6-C1(r芳基的殘基取代一或二次之胺基；或具下列化學式(II)之一種經二取代的胺基： 20 Γ~\ —N W Ή7] °(ΙΙ) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-Cr烷基，及其中化學式(II)中的亞甲基可選擇性地被Ci_C6-烧基、氣代基或氯代基取代一或二次。 49.如申請專利範圍第41至48項中任一項之化合物，其中Y 165 200932732 10 代表被下列各者取代一或多次之苯基： aKVQ-烧基、C6-C10-芳基、C6-C10-芳基_CrC6_烧基、Q-CV烧氧基、C6-C10-芳氧基、C6-C1(r芳基烷氧基，其中各者選擇性地被下列各者取代一次或多次：CVCV烷基；CVC6-烷氧基；so3h ; C02H ;胺基；經選自下列群中的殘基取代一或多次之胺基： Ci-C6-烧基、C6-Ci〇-方基、C6-Ci〇-方基-Ci-C。-烧基、 Ci_C6_烧基幾基、C6-Ci〇-^r基幾基、Ci-C6_烧基>6黃酿基及C6-ClQ-芳基項酿基，硫Hi基，經基，確基；氛基；氟代基；氣代基；溴代基；碘代基；cf3 ; conh2 ; S〇2NH2; 〇CF3 ;或其中該胺基官能度被(^-(：6-烷基取代一次或二次之CONH2或S02NH2 ; 或被：Cyano; fluorinated; selected from fluoro, carbyl, bromo or mothyl; CF3; OCF3; or a saturated, unsaturated or aromatic complex consisting of up to 10 atoms A ring system, which is optionally substituted one or more times by: Ci-CV: ^ group; Ci-C6_houseneoxy; C〇〇H; so3h · 158 20 200932732 CONH2 ; S02NH2 ; CONH2 or So2nh2, wherein the amino functionality is substituted one or more times by a residue selected from the group consisting of Crc6-alkyl, C6-C1()-aryl or C6-C1 (raryl-CVC4-alkyl, and in one In the case of a dialkyl substituted amine functionality, the alkyl residue 5 group can be combined to form a 5 or 6 membered ring; an amine group; one or more amine groups substituted with a residue selected from the group consisting of :CrC6-alkyl, C6-C10-aryl, C6-C1 (raryl-OC4-alkyl, crc6-alkylcarbonyl, c6-c1()-arylcarbonyl, crc6-alkylsulfonyl and C6-c1 (rarylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; gas 10; bromo; iodo; CF3 or OCF3; and R1 to R5 thereof Any two or more of them can be combined to form a fused saturation, a saturated or aromatic homocyclic or heterocyclic ring system; η represents 0; m represents 0; Y represents a phenyl group which is optionally substituted by one or more of the following: 15 a) C!-C6-alkyl, C6- Ci〇-square, C6-C!-aryl-Ci_C8_alkyl, CrCV alkoxy, C6-C10-aryloxy, C6-C1 (raryl-CVC8-alkoxy, CrCV alkoxylate Carbonyl group, C6-C1 (r aryloxycarbonyl group, C6_Ci〇-^• group-Ci_C8-lactyl group, Ci_C6_alkyl group, c6-c1 (r arylcarbonyl, c6-c1()- Aryl-crc8-alkylcarbonyl, crc6-20 alkyl group, C6-Ci〇-aryl group, C1-C6-alkylthio group, c6-c1()-arylthio group, Q -CV alkylmercaptocarbonyl, c3-c8-cycloalkylfluorenylcarbonyl, C6-C1Q-aryldecylcarbonyl, CVC6-alkylindenylcarboxy, C6-C1()-aryldecylcarboxy, CkQ-alkane Sulfosyl, c6-c10-arylsulfonyl, crc6-alkyloxythio, c6-c1()-aryloxythio; 159 200932732 wherein each is optionally replaced by one or the following Multiple times: Cj-CV alkyl; crc6-alkoxy; conh2 or so2nh2 selectively substituted by crc6-alkyl one or two; so3h; co2h; amine group; residue selected from the following group One or more amines 5 groups: CrCV alkyl, C6-C10-aryl, C6-C10-aryl-CVC4-alkyl, Ci-C6-alkyl group, C6-Ci〇-^ , Ci_C6-alkylsulfonyl and C6-C1()-arylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; chloro; bromo; iodo; Cf3 or ocf3; 10 wherein the number of such selective substituents may combine to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; or b) the species is saturated with up to 10 atoms An unsaturated or aromatic heterocyclic ring system which is optionally substituted one or more times by the following: OC6-alkyl; CkCV alkoxy; COOH; optionally substituted by 15 CVC6-alkyl a second conh2 or so2nh2; so3h; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of Ci_C6_alkyl, C6-Ci〇-aryl, C6_Ci〇-aryl-C1- C4-alkyl, CrCV alkylcarbonyl, C6-C1()-arylcarbonyl, (VCV alkylsulfonyl and (:6-(:1()-arylsulfonyl; sulfhydryl; hydroxy; Nitro; cyano; 20 fluoro; chloro; bromo; iodo; CF3 or OCF3 Or C) hydroxy; sulfhydryl; nitro; cyano; fluoro; chloro; bromo; iodo; cf3; ocf3; co2h; S03H; conh2; so2nh2; conh2 or so2nh2, where The amine functionality is selected one or more times by the residue of IQ-Ce-alkyl, C6-C1 (r-aryl or C6-C1()-aryl-CrC4-200932732 5 alkyl" and In the case of a di-Crc6-alkyl substituted amine functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; one or more amines substituted with a residue selected from the group consisting of one or more Base: CrC6-alkyl, C6-C1 (r aryl, C6-C10-aryl-CrC8-alkyl, CrC6-alkylcarbonyl, C6-C1 (rarylcarbonyl, CVC6-alkylsulfonyl and C6-c1 (rarylsulfonyl; a disubstituted amino group of the following formula (IV): /~\ ❹ W ° (IV) wherein 〇 represents 0 or 1 ' and W represents oxygen, CH 2 or NR 6 R6 is selected from the group consisting of hydrogen and CrCV alkyl, and the methylene group of the formula (1) is optionally substituted by one or two (^-(: 4-alkyl, fluoro or chloro group) Or one of its stereoisomers, pharmaceutically acceptable salts or esters or precursor drugs; The month 1J is: 15 ❹ a) R2 or R4 does not represent a substituent c(=A)_N(B)_s〇2_NR6R7, where A represents oxygen or sulfur, and B represents hydrogen, cyano, Ci_c6_alkyl, Ci_C6_ An oxy-alkyl group, a c3-c7-cycloalkyl group, a C3_C6_dilute hydrocarbon group, a C3_c6-fast group or a selectively substituted aryl group derivative, and the R6 and r7 systems 20 independently of each other represent hydrogen or an organic residue The base or together represent an organic cyclic structure; b) when Y represents an unsubstituted phenyl group, "to the rule 5 is independent of each other and does not represent hydrogen, _yl 1 phenyl, chloro, wei or or Radical; 161 200932732 c) R2 or R4 does not represent a pyrazol-3-yl-derivative; and d) the phenyl ring substituted with R1 to R5 and Y do not represent the following combinations: benzene substituted by R1 to R5 Base ring Y 2-phenylphenyl 4-phenylphenyl 2,3-dimercaptophenyl 4-phenylphenyl 2,4-diphenylphenyl 4-phenylphenyl 2-chloro-3-methylphenyl 4-Phenylphenyl 2,5-difluorophenyl 4-methylphenyl 2-methoxy-4-indolyl 4-phenylphenyl 2-phenylphenyl 4-mercaptophenyl 2,6- Diphenyl phenyl 4-phenylphenyl 2-(trifluoromethylhydrothio)phenylphenyl 2,3,4-trimethylphenyl 4-gas Base 2,5-difluorophenyl 4->odor phenyl 2,4-dimethylphenyl 4-phenylphenyl 4-phenylphenyl 4-phenylphenyl 3-phenylphenyl 4-phenylphenyl 4-bromophenyl 4-epoxyphenyl 2-phenylphenyl 4-bromophenyl 2,5-difluorophenyl 4-phenylphenyl 4-phenylphenyl 4-bromophenyl 3,5-dimethyl Phenyl 4-phenylphenyl 4-trifluoromethoxyphenyl 4-octylphenyl 4-trifluoromethoxyphenyl 3-phenoxyphenyl 2,3-dihydro-2,2-di Methyl-7-benzofuranylphenyl 42. A compound according to claim 41, wherein R1 to R5 are independently represented by each other: hydrogen; hydroxy; 200932732 5 Ci-C6-alkyl, C6-Ci 〇-square, Ci_C6-aerate, C6-Ci〇-aryloxy, C6-C10-aryl-CrC6-alkoxy, QQ-alkylcarboxy, C6_Ci〇-^-based, Ci_C6_ Base-based, C6-Ci〇-aryl base, each of which is optionally substituted one or more times by: Ci_C6_alkyl, Ci_C6-homolyl, amine, Ci-Cg- Anthracene, di-Ci_C6-alkylamino, light, gas, carbyl, thio, cyano, CF3 or OCF3; amine; ❹ selected from crc6-alkyl, c6- C10-aryl residue One or more 10 amino groups; 1-pyrrolyl, 2-pyrrolyl or 3-pyrrolyl, which are optionally taken from one or more residues selected from the group consisting of RQ-Qr alkyl, amine, fluorine Substituted, chloro or CF3; a disubstituted amino group of the following formula (II): 15 ❿ —NW ° (II) wherein 〇 represents 〇 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 It is selected from hydrogen and CrC6-alkyl, and the methylene group in the formula (II) thereof may be optionally substituted one or two times with a CrCV alkyl group, a fluoro group or a chloro group; conh2; 20 so2nh2; CONH2 or S02NH2 Wherein the amino functionality is selected from the group consisting of crc6-alkyl or c6-c1 (residyl of the raryl group substituted one or two times; a sharp group; 163 200932732 gas group; bromo group; cf3; or OCF3. The compound of claim 41 or 42, wherein one or more of R1 or R5 represents hydrogen, gas or chlorine. 44. A compound according to claim 43 wherein R1 or R5 represents hydrogen or fluorine. The compound of any one of claims 41 to 44, wherein one or more of R1 10 or R5 represents: a thiol group; or a Ci-C6-alkoxy group, a C6-Ci 〇-aryloxy group , C6-Ci〇-aryl-Ci_C6-alkoxy, CVC6-alkylcarboxy, C6-C1()-arylcarboxy, CVCV alkylsulfonyl, c6-c1()-arylsulfonyl , each of which is optionally substituted one or more times by each of the following 15 columns: CVCV alkyl, CVCV alkoxy, amine, CVC6-alkylamino, di-CVCV alkylamino, optionally CrC6-alkyl or C6-C1()-aryl substituted one or two times of CONH2 or S02NH2, hydroxy, fluoro, carbyl, bromo, cyano, CF3 or OCF3. 20. The compound of claim 45, wherein one of R2, R3 or R4 represents a hydroxyl group; or crc6-alkoxy, C6-C10-aryloxy or c6-c10-aryl-crc6- Alkoxy, each of which is optionally substituted one or more times by: CrC6-alkyl, CrC6-alkoxy, amine, CVCV alkylamino, 200932732 5 di-CrC6-alkylamine Optionally, one or two of conh2 or so2nh2, hydroxy, fluoro, carbyl or bromo are substituted by CVC6-alkyl or c6-c10-aryl. The compound according to any one of claims 41 to 46, wherein one or more of R1 to R5 represents an amine group; and is substituted with a residue selected from the group consisting of CrC6-alkyl and C6-C10-aryl One or more amine groups; or a disubstituted amine group of the following formula (II): !~\ —NW H7] °(11) 羲10 where 0 represents 0 or 1, and W represents oxygen, CH2 or NR6, R6 is selected from the group consisting of hydrogen and Q-CV alkyl, and the methylene group in the formula (II) may be optionally substituted one or two times with a Q-CV alkyl group, a fluoro group or a gas group. . 48. The compound of claim 47, wherein one of R2, R3 or R4 represents an amine group; 15 ❹ is substituted by a residue selected from the group consisting of CrC6-alkyl and C6-C1 (r-aryl) Amino group; or a disubstituted amino group of the following formula (II): 20 Γ~\ —NW Ή7] °(ΙΙ) where 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 It is selected from the group consisting of hydrogen and Q-Cr alkyl, and the methylene group in the chemical formula (II) thereof may be optionally substituted one or two times with a Ci_C6-alkyl group, a gas group or a chloro group. The compound of any one of items 41 to 48, wherein Y 165 200932732 10 represents a phenyl group substituted by one or more of the following: aKVQ-alkyl, C6-C10-aryl, C6-C10-aryl _CrC6_alkyl, Q-CV alkoxy, C6-C10-aryloxy, C6-C1 (raryl alkoxy, each of which is optionally substituted one or more times by: CVCV alkane a group; CVC6-alkoxy; so3h; C02H; an amine group; an amine group substituted one or more times with a residue selected from the group consisting of Ci-C6-alkyl, C6-Ci〇-square, C6- Ci〇-square-Ci-C.-alkyl, Ci_C6_alkyl group, C6-Ci 〇-^r yl group, Ci-C6_alkyl group>6 yellow wine base and C6-ClQ-aryl base, sulfur Hi group, thiol group, aryl group; fluoro group; a bromo group; an iodo group; cf3; conh2; S〇2NH2; 〇CF3; or wherein the amine functionality is replaced by (^-(6-alkyl substituted once or twice CONH2 or S02NH2; :

15 20 b)羥基；硫氫基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；cf3 ; ocf3 ; co2H ; so3H ; conh2 ; so2nh2 ;或conh2或so2nh2，其中該胺基官能度被CVCV烧基、C6-C10-芳基、C6-C10-芳基-CVQ-烧基取代一次或二次，及其中在一種經二-CrC6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6 貝環，胺基，被C^-C6-烧基或苯基取代一或多次之胺基；具下列化學式(II)之一種經二取代的胺基：15 20 b) hydroxy; sulfhydryl; nitro; cyano; fluoro; ke group; bromo; iodo; cf3; ocf3; co2H; so3H; conh2; so2nh2; or conh2 or so2nh2, wherein The amine functionality is substituted once or twice with CVCV alkyl, C6-C10-aryl, C6-C10-aryl-CVQ-alkyl, and wherein one is substituted with a di-CrC6-alkyl group. In the case of a degree, the alkyl residue may be bonded to form a 5 or 6-shell ring, an amine group, an amine group substituted one or more times by a C^-C6-alkyl group or a phenyl group; and having the following chemical formula (II) A disubstituted amine group:

-N/_XW-N/_XW

(II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選 166 200932732 自氫與crc6-烷基，及其中化學式(II)中的亞甲基可選擇性地被CrCV烷基、氟代基或氣代基取代一或二次；或被： C)一種由至多10個原子組成之飽和、不飽和或芳 5 族雜環式環系統，其選擇性地被下列各者取代一或多次：CrC6-烷基；CrC6-烷氧基；COOH ; CONH2 ; S〇2NH2 ;其中該胺基官能度被CrC6-烷基取代一次或 -—次之CONH2或SO2NH2，該Ci_C6-烧基可結合而形成5 ® 或6員環；S03H ;胺基；經選自下列群中的殘基取代 10 —或多次之胺基：crc6-烷基、c6-c10-芳基、c6-c10-芳基-CVC6-烷基、crc6-烷基羰基、c6-c1(r芳基羰基、 Ci-CV烧基績醯基及C6-Ci〇-芳基績酿基；硫氫基；經基，硝基；氰基；氟代基；氯代基；漠代基；蛾代基;cf3 ;或〇cf3。 15 50.如申請專利範圍第49項之化合物，其中Y為被下列各者取代一或多次之苯基：Q-C6-烷基；苯基；crC6-烷氧基；羥基；氟代基；氯代基；溴代基；cf3 ; ocf3 ;胺基；或選擇性地被CrC6-烧基取代一或二次之c〇NH2，其中該等選擇性的Ci-CV烧基殘基可結合而形成5或6員 20 環。 51·如申請專利範圍第50項之化合物，其中γ為苯基，其被羥基、氟代基、氣代基或溴代基取代一或二次。 52.如申請專利範圍第50項之化合物，其中γ為苯基，其在 4-位置被氟代基或被氯代基取代、在2-與4-位置被氟代 167 200932732 基取代、在2-與4-位置被氣代基取代或在4-位置被苯基取代。 53. 如申請專利範圍第41項之化合物，其中Y為被氟代基、氣代基或溴代基取代一或二次之苯基；及R2至R4中之任一者代表OR7，其中R7係選自氫與CrC6-烷基。 54. 如申請專利範圍第53項之化合物，其中γ為苯基，其在 4-位置被氟代基或被氣代基取代、在2-與4-位置被氟代基取代或在2-與4-位置被氣代基取代。 55. 如申請專利範圍第53或54項之化合物，其中R1或R5代表 © 氟或氫。 56. 如申6青專利範圍第53至55項中任一項之化合物，其中R3 - 或者R3與R4代表羥基。 — 57. —種具化學式⑴的化合物：(II) wherein 〇 represents 0 or 1, and W represents oxygen, CH2 or NR6, and R6 is selected from 166 200932732 from hydrogen and crc6-alkyl, and wherein the methylene group in formula (II) is selectively substituted by CrCV a fluoro, fluoro or aldehyde group substituted one or two times; or by: C) a saturated, unsaturated or aryl 5-membered heterocyclic ring system consisting of up to 10 atoms, optionally selected by Substituted one or more times: CrC6-alkyl; CrC6-alkoxy; COOH; CONH2; S〇2NH2; wherein the amine functionality is replaced by CrC6-alkyl once or - secondly CONH2 or SO2NH2, the Ci_C6- The alkyl groups may be combined to form a 5 ® or 6 membered ring; S03H; an amine group; 10 or more amine groups substituted with a residue selected from the group consisting of: crc6-alkyl, c6-c10-aryl, c6 -c10-aryl-CVC6-alkyl, crc6-alkylcarbonyl, c6-c1 (rarylcarbonyl, Ci-CV alkyl thiol and C6-Ci〇-aryl aryl; thiol; Base group, nitro group; cyano group; fluoro group; chloro group; moiety group; moth base; cf3; or 〇cf3. 15 50. The compound of claim 49, wherein Y is the following Replace one or more benzene :Q-C6-alkyl; phenyl; crC6-alkoxy; hydroxy; fluoro; chloro; bromo; cf3; ocf3; amine; or alternatively substituted by CrC6-alkyl a secondary c〇NH2, wherein the selective Ci-CV alkyl residue can be combined to form a 5 or 6 member 20 ring. 51. A compound according to claim 50, wherein γ is a phenyl group, Substituted one or two times by a hydroxyl group, a fluoro group, a gas group or a bromo group. 52. A compound according to claim 50, wherein γ is a phenyl group which is fluorinated or chlorine at the 4-position Substituted, substituted at the 2- and 4- positions by a fluoro-167 200932732 group, substituted at the 2- and 4-positions by a gas group or at the 4-position by a phenyl group. 53. a compound wherein Y is a phenyl group substituted one or two times by a fluoro group, a gas group or a bromo group; and any one of R2 to R4 represents OR7, wherein R7 is selected from the group consisting of hydrogen and CrC6-alkyl 54. The compound of claim 53, wherein γ is phenyl, which is substituted at the 4-position with a fluoro group or by a gas group, at the 2- and 4-positions by a fluoro group or The 2- and 4-positions are substituted by a gas group. 55. A compound according to claim 53 or 54 wherein R1 or R5 represents © fluorine or hydrogen. 56. A compound according to any of the preceding claims, wherein R3 - or R3 and R4 represent a hydroxy group. — 57. — A compound of formula (1):

其中R1或R5為氫或氟； R至尺中之任-者代表經基，而其他的R殘基為：氫； ^ Cl_CV烧基、C3-C8-環烧基、C6-C1()-芳基、c6-c10-方基-Cl-C8_燒基、Ci_C6-烧氧基、C6-C1(r芳氧基、 ^Cur方基-CVCV燒氧基、Ci_C6炫氧基幾基、c6_c】『芳氧基m基' c6<v芳基_Ci_C8烧氧基絲、Ci_C6烧 168 200932732Wherein R1 or R5 is hydrogen or fluorine; R to the ruler represents a meridine, and the other R residues are: hydrogen; ^ Cl_CV alkyl, C3-C8-cycloalkyl, C6-C1()- Aryl, c6-c10-aryl-Cl-C8_alkyl, Ci_C6-alkoxy, C6-C1 (r aryloxy, ^Cur aryl-CVCV alkoxy, Ci_C6 methoxyl group, c6_c 】"Aryloxym-based 'c6<v-aryl_Ci_C8 alkoxylated wire, Ci_C6 168 </ br> 200932732

1010

基羰基、c6-c1(r芳基羰基、C6-C10-芳基-Ci-CV烷基羰基、CrC6-烷基羧基、C6-C1(r芳基羧基、CrCV烷基氫硫基、c6-c1(r芳基氫硫基、q-cv烷基酼基羰基、 C3-C8-環烷基巯基羰基、C6-C10-芳基Μ基羰基、CrC6-烷基巯基羧基、c6-c1(r芳基酼基羧基、CVC6-烷基磺醯基、c6-c10-芳基磺醯基、crc6-烷基氧硫基、c6-c10-芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次：crc6-烷基、crc6-烷氧基、c6-c1(r芳氧基、 C02H、S03H、胺基、crc6-烷基胺基、二-crc6-烷基胺基、硫氫基、羥基、硝基、氰基、氟代基、氣代基、溴代基、碘代基、CF3或OCF3 ; co2h ； so3h ; 胺基；經選自下列群中的殘基取代一或多次之胺基： Ci-C6-烧基、C6-Ci〇-芳基、C6_Ci(T 芳基-Ci-C6_ 炫基、 Ci_C6_烧基幾基、C6-Ci〇-芳基幾基、Ci-C6_烧基續酿基及C6-CiQ-方基績酿基；具下列化學式(II)之一種經二取代的胺基： —N W Η7] ο (II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Ci-Cr烷基，及其中化學式(II)中的亞甲基可選擇性地被Ci-CV烷基、氟代基或氣代基取代一或二次； 169 20 200932732 conh2 ； so2nh2 ; 5 10 15 conh2或so2nh2，其中該胺基官能度被選自 crc6-烷基、C6-C1(r芳基或C6-C1Q-芳基-CVCV烷基的殘基取代一次或多次：及其中在一種經二-CVC6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5 或6員環；硫氫基；經基； ί肖基；氰基；氟磺醯基；選自氟代基、氣代基、溴代基或碘代基之鹵素； CF3 ; OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次；CrCV烷基、CVCV烷氧基、COOH、S03H、胺基、硫氫基、羥基、硝基、氰基、氟代基、氯代基、溴代基、碘代基、CF3或OCF3 ; 及其中R2至R4中之二或多者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統； η與m為0 ;及 Y為被下列各者取代一或多次之苯基：CrC6-烷 20 200932732 基；苯基；CrCV烷氧基；羥基；氟代基；氣代基；溴代基；CF3 ; OCF3 ;胺基；或選擇性地被crc6-烷基取代一或二次之CONH2，其中該等選擇性的crc6-烷基殘基可結合而形成5或6員環；或其一種立體異構物、藥學上可接受的鹽類或酯或前驅藥物。 58.—種具化學式（I)的化合物：Carbonyl group, c6-c1 (r arylcarbonyl group, C6-C10-aryl-Ci-CV alkylcarbonyl group, CrC6-alkylcarboxy group, C6-C1 (r arylcarboxy group, CrCV alkyl thiol group, c6-) C1(rarylthiothio, q-cvalkylmercaptocarbonyl, C3-C8-cycloalkylfluorenylcarbonyl, C6-C10-aryldecylcarbonyl, CrC6-alkylindenylcarboxy, c6-c1(r Aryl fluorenylcarboxy, CVC6-alkylsulfonyl, c6-c10-arylsulfonyl, crc6-alkyloxythio, c6-c10-aryloxythio, each of which is selectively Each one is substituted one or more times: crc6-alkyl, crc6-alkoxy, c6-c1 (r aryloxy, C02H, S03H, amine, crc6-alkylamino, bis-rcc6-alkylamino , sulfhydryl, hydroxy, nitro, cyano, fluoro, carbyl, bromo, iodo, CF3 or OCF3; co2h; so3h; amine; substituted by a residue selected from the group below One or more amine groups: Ci-C6-alkyl, C6-Ci〇-aryl, C6_Ci (T aryl-Ci-C6_ 炫, Ci_C6_alkyl group, C6-Ci〇-aryl Base, Ci-C6_alkyl base and C6-CiQ-square base; a disubstituted amine group of the following formula (II): -NW Η7] ο (II) wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and Ci-Cr alkyl, and the methylene group in the formula (II) is optionally Ci- CV alkyl, fluoro or ke group substituted one or two times; 169 20 200932732 conh2 ; so2nh2 ; 5 10 15 conh2 or so2nh2, wherein the amine functionality is selected from the group consisting of crc6-alkyl, C6-C1 (r Residues of an aryl or C6-C1Q-aryl-CVCV alkyl group substituted one or more times: and in the case of a di-CVC6-alkyl substituted amine functionality, the alkyl residue can be combined And forming a 5- or 6-membered ring; a sulfhydryl group; a thiol group; a cyano group; a fluorosulfonyl group; a halogen selected from a fluoro group, a gas group, a bromo group or an iodo group; CF3; OCF3 Or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, which is optionally substituted one or more times by: CrCV alkyl, CVCV alkoxy, COOH, S03H, Amino, sulfhydryl, hydroxy, nitro, cyano, fluoro, chloro, bromo, iodo, CF3 or OCF3; and two or more of R2 to R4 thereof Condensed to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; η and m are 0; and Y is a phenyl group substituted by one or more of the following: CrC6-alkane 20 200932732 base; benzene a group; a CrCV alkoxy group; a hydroxyl group; a fluoro group; a gas group; a bromo group; a CF3; an OCF3; an amine group; or a CONH2 which is optionally substituted by a crc6-alkyl group one or two times, wherein the selectivity The crc6-alkyl residue may be combined to form a 5 or 6 membered ring; or a stereoisomer thereof, a pharmaceutically acceptable salt or ester or a prodrug. 58. - A compound of formula (I):

❹ 10 ❹ 其中R1或R5為氫或氟； R2至R4中之任一者代表胺基，而其他的R殘基為： CrC6-烷基、C3-C8-環烷基、C6-C1()-芳基、C6-C10-芳基-CkQ-烷基、cvcv烷氧基、C6-C10-芳氧基、 C6-C1()-芳基-CVCV烷氧基、CrC6-烷氧基羰基、C6-C10-芳氧基叛基、C6_Ci〇-芳基-Ci-Cg-烧氧基幾基、C1-C6-烧基羰基、C6-Cnr芳基羰基、C6-C1(r芳基-CVQ-烷基羰基、CrC6-烷基羧基、C6-C1(r芳基羧基、q-cv烷基氫硫基、C6-C1()-芳基氩硫基、Q-CV烷基酼基羰基、 C3-C8-環烷基巯基羰基、C6-C1(r芳基巯基羰基、q-cv 烷基巯基羧基、C6-C1Q-芳基Μ基羧基、CrC^-烷基磺醯基、C6-Ci〇-芳基績酿基、Ci-Ce-炫《基氧硫基、C6-Ci〇-芳 171 200932732 基氧硫基，其中各者選擇性地被下列各者取代一次或多次：Ci-C6-炫•基、Ci-C6-炫•氧基、C6_C1(d 乳基、 c〇2H、s〇3H、胺基、CrCV炫基胺基、二-Q-CV烧基胺基、硫氫基、羥基、硝基、氰基、氟代基、氣代基、溴代基、碘代基、Cp3或0cp3， C02H ; so3H; 胺基，經選自下列群中的殘基取代一或多次之胺基： 0 CrC6-炫基、CrCi。-芳基、c6-Ci〇-芳基-Ci-C6-烧基、 CrC6_炫基幾基、C6-C10-芳基羰基、CrCV烷基磺醯基 - 及C6-C1()-芳基磺酿基； - 具下列化學式(Π)之一種經二取代的胺基： 0 (II) 其中〇代表0或1 ’而|代表氧、CH2或nr6，R6係選自氫與CVCV烷基’及其中化學式(11)中的亞甲基可選擇〇性地被Ci-C6-炫基、氟代基或氣代基取代一或二次； CONH2 ; S02NH2; 20 conh2或so2nh2，其中該胺基官能度被選自Crc6- 烷基、c6-c1()-芳基或c6-c1(r芳基-crc6-烧基的殘基取代一次或多次，及其中在一種經二-CrCV烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環； 172 200932732 硫氫基；羥基；硝基；氰基； 5 氟磺醯基；選自氟代基、氣代基、溴代基或峨代基之函素； cf3 ； ❺ 10 〇cf3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次： Ci-C6-烷基、CrQ-烷氧基、COOH、S03H、胺基、硫氫基、羥基、硝基、氰基、氟代基、氯代基、溴代基、碘代基、cf3或ocf3 ; 15 及其中R2至R4中之任二或多者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統； η與m為0 ;及 20 Y為被下列各者取代一或多次之苯基：CrC6-烷基；苯基；CrC6-烷氧基；羥基；氟代基；氣代基；溴代基；CF3 ; OCF3 ;胺基；或選擇性地被Crc6_烷基取代一或二次之CONH2，其中該等選擇性的Cl_c6_烷基殘基可結合而形成5或6員環；或其一種立體異構物、藥學上可接受的鹽類或酯或前驅藥物。 59.—種具化學式⑴的化合物： 173 200932732❹ 10 ❹ wherein R1 or R5 is hydrogen or fluorine; any of R2 to R4 represents an amine group, and the other R residues are: CrC6-alkyl, C3-C8-cycloalkyl, C6-C1() -aryl, C6-C10-aryl-CkQ-alkyl, cvcv alkoxy, C6-C10-aryloxy, C6-C1()-aryl-CVCV alkoxy, CrC6-alkoxycarbonyl, C6-C10-aryloxy-reactive, C6_Ci〇-aryl-Ci-Cg-alkoxy group, C1-C6-alkylcarbonyl, C6-Cnr arylcarbonyl, C6-C1(r-aryl-CVQ -alkylcarbonyl, CrC6-alkylcarboxy, C6-C1 (rarylcarboxy, q-cv alkylthiothio, C6-C1()-arylsulfothio, Q-CV alkylthiocarbonyl, C3-C8-cycloalkylfluorenylcarbonyl, C6-C1 (rarylcarbonylcarbonyl, q-cvalkylmercaptocarboxy, C6-C1Q-aryldecylcarboxy, CrC^-alkylsulfonyl, C6-Ci 〇-aryl base, Ci-Ce-Hyun "yloxythio", C6-Ci〇-aryl 171 200932732 oxythio group, each of which is optionally substituted one or more times by: Ci- C6-Hyun·Base, Ci-C6-Hyun•oxy, C6_C1 (d-milyl, c〇2H, s〇3H, amine group, CrCV-based amine group, di-Q-CV alkylamino group, sulfuric acid Base, hydroxyl, nitro, cyano, fluorine Substituent, carbyl, bromo, iodo, Cp3 or 0cp3, C02H; so3H; an amine group, one or more amine groups substituted with a residue selected from the group consisting of: 0 CrC6-croplex, CrCi.-aryl, c6-Ci〇-aryl-Ci-C6-alkyl, CrC6-Huntyl, C6-C10-arylcarbonyl, CrCV alkylsulfonyl- and C6-C1()- An aryl sulfonyl group; - a disubstituted amino group having the formula (Π): 0 (II) wherein 〇 represents 0 or 1 ' and | represents oxygen, CH 2 or nr 6 , and R 6 is selected from hydrogen and CVC V alkane The methylene group in the formula 'and its intermediate formula (11) may be optionally substituted one or two times with a Ci-C6-dishyl group, a fluoro group or a gas group; CONH2; S02NH2; 20 conh2 or so2nh2, wherein The amino functionality is substituted one or more times by a residue selected from the group consisting of Crc6-alkyl, c6-c1()-aryl or c6-c1 (raryl-crc6-alkyl), and in one of the di-CrCV In the case of an alkyl substituted amine functionality, the alkyl residue may combine to form a 5 or 6 membered ring; 172 200932732 sulfhydryl; hydroxy; nitro; cyano; 5 fluorosulfonyl; Substituent, gas-based, bromo or deuterated a singly; cf3; ❺ 10 〇 cf3 ; or a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, which is optionally substituted one or more times by: Ci-C6- Alkyl, CrQ-alkoxy, COOH, S03H, amine, sulfhydryl, hydroxy, nitro, cyano, fluoro, chloro, bromo, iodo, cf3 or ocf3; Wherein two or more of R2 to R4 may be combined to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; η and m are 0; and 20 Y is substituted by one or more of the following: Lower phenyl: CrC6-alkyl; phenyl; CrC6-alkoxy; hydroxy; fluoro; ketone; bromo; CF3; OCF3; amine; or alternatively substituted by Crc6-alkyl One or two times of CONH2, wherein the selective Cl_c6-alkyl residues may be combined to form a 5 or 6 membered ring; or a stereoisomer thereof, a pharmaceutically acceptable salt or ester or a prodrug. 59.—A compound of formula (1): 173 200932732

(i) 其中R1或R5為氫或氟； R3或R4中之一者為CrC6-烷氧基、C6-C10-芳氧 5 基、C6-C1(r芳基-CrC8-烷氧基、CrC6-烷基羧基、 C6-C1()-芳基羧基、Q-CV烷基巯基羧基、C6-C1(r芳基输基叛基、Ci_C6_烧基氧硫基、CVCiq-芳基氧硫基’其 © 中各者選擇性地被下列各者取代一次或多次：crc6-烷基、CVCV烷氧基、c6-c10-芳氧基、co2H、so3H、 ' 10 胺基、Ci_C6_烧基胺基、二-Ci_C6_烧基胺基、硫氮 · 基、經基、确基、氰基、氟代基、氯代基、>臭代基、碘代基、CF3或OCF3 ; R3或R4中之另一者係經選自下列群中的殘基取代一或多次之胺基：Ci_C6_烧基、C6-Ci〇-芳基、C6-Ci〇-15 芳基-CrCV烷基、CVCV烷基羰基、c6-c1(r芳基羰 ® 基、CVCV烷基磺醯基及c6-c1()-芳基磺醯基；及R2為：氫； Ci-CV烷基、c3-c8-環烷基、c6-c1()-芳基、c6-c10-20 芳基-C1-C8-烧基、Ci_C6_烧氧基、C6_Ci〇-芳氧基、C6_Ci〇_ 芳基-crc8-烷氧基、crc6-烷氧基羰基、C6-C1Q-芳氧基-羰基、c6-c10-芳基-CrC8-烷氧基羰基、CVCV烷基羰 174 200932732 基、c6-c1()-芳基羰基、c6-c10-芳基-crc8-烷基羰基、 CrC6-烷基羧基、C6-C1()-芳基羧基、CVCV烷基氫硫基、 C6-C1(r芳基氫硫基、CrC6-烷基Μ基羰基、C3-C8-環烷基巯基羰基、C6-C1()-芳基巯基羰基、CVCV烷基Μ基羧 5 基、C6-C1()-芳基Μ基羧基、Q-CV烷基磺醯基、C6-C10- 芳基磺醯基、CrC6-烷基氧硫基、C6-C1()-芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次：crc6-烷基、Ci-CV烷氧基、c6-c1(r芳氧基、co2h、so3h、 ® 胺基、CVCV烷基胺基、二-CVC6-烷基胺基、硫氫基、 10 經基、确基、氰基、氟代基、氯代基、漠代基、峨代基、 CF3 或 OCF3 ; • co2h ; so3h ; 胺基； 15 經選自下列群中的殘基取代一或多次之胺基： crc6-烷基、C6-C1()-芳基、C6-C10-芳基-Q-C6-烷基、 Crc6-烷基羰基、C6-C1(r芳基羰基、CrC6-烷基磺醯基及C6_CiQ-芳基績酿基；具下列化學式(II)之一種經二取代的胺基： —N W 20 °(11) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與C! -C6-烷基，及其中化學式(II)中的亞甲基可選擇性地被crc6-烷基、氟代基或氯代基取代一或二次； 175 200932732 conh2 ； so2nh2 ; conh2或so2nh2，其中該胺基官能度被選自 crc6-烷基、C6-C1(r芳基或C6-C1(r芳基-CrCV烷基的殘 5 基取代一次或多次，及其中在一種經二-c^-cv烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或 6員環；硫氫基；羥基； ❹ 10 硝基；氰基； 1 氣績酿基， - 選自氟代基、氯代基、漠代基或峨代基之鹵素； CF3 ; 15 OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次： CrQ-烷基、CkCV烷氧基、COOH、S03H、胺基、硫氫基、經基、頌基、氰基、氟代基、氯代基、漠代 20 基、碘代基、CF3或OCF3 ; η與m為0 ;及 Y為苯基，其被下列各者取代一或多次：CrC6-烷基；苯基；Q-CV烷氧基；羥基；氟代基；氯代基；溴代基；CF3 ; OCF3 ;胺基；或選擇性地被CrC6-烷基 176 200932732 取代一或二次之CONH2，其中該等選擇性的CVCV烷基殘基可結合而形成5或6員環；或其一種立體異構物、藥學上可接受的鹽類或酯或前驅藥物。 5 Ο 10 15 60. 如申請專利範圍第57至59項中任一項之化合物，其中Y 為被下列各者取代一或多次之苯基：CVQ-烷基；苯基；Ci_C6_烧氧基；經基；氟代基；氯代基；漠代基； CF3 ; OCF3 ;胺基；或選擇性地被Q-C6-烷基取代一或二次之CONH2，其中該等選擇性的CVCV烷基殘基可結合而形成5或6員環。 61. 如申請專利範圍第60項之化合物，其中Y為被羥基、氟代基、氯代基或溴代基取代一或二次之苯基。 62. 如申請專利範圍第60項之化合物，其中Y為苯基，其在 4-位置被氟代基或被氣代基取代、在2-與4-位置被氟代基取代、在2-與4-位置被氯代基取代或在4-位置被苯基取代。 63. —種具化學式(I)的化合物：(i) wherein R1 or R5 is hydrogen or fluorine; one of R3 or R4 is CrC6-alkoxy, C6-C10-aryloxy-5, C6-C1 (raryl-CrC8-alkoxy, CrC6 -alkylcarboxy, C6-C1()-arylcarboxy, Q-CV alkylmercaptocarboxy, C6-C1 (rarylalkylthio, Ci_C6_alkyloxythio, CVCiq-aryloxythio) Each of them is optionally substituted one or more times by: crc6-alkyl, CVCV alkoxy, c6-c10-aryloxy, co2H, so3H, '10 amine, Ci_C6_alkyl Amino, di-Ci_C6-alkylamino, thiazolidine, thiol, decyl, cyano, fluoro, chloro, > odoryl, iodo, CF3 or OCF3; R3 or The other of R4 is an amine group substituted one or more times with a residue selected from the group consisting of Ci_C6_alkyl, C6-Ci〇-aryl, C6-Ci〇-15 aryl-CrCV alkyl , CVCV alkylcarbonyl, c6-c1 (rarylcarbonyl), CVCV alkylsulfonyl and c6-c1()-arylsulfonyl; and R2 are: hydrogen; Ci-CV alkyl, c3- C8-cycloalkyl, c6-c1()-aryl, c6-c10-20 aryl-C1-C8-alkyl, Ci_C6_alkoxy, C6_Ci〇-aryloxy, C6_Ci〇_ aryl-crc8 -alkoxy Crc6-alkoxycarbonyl, C6-C1Q-aryloxy-carbonyl, c6-c10-aryl-CrC8-alkoxycarbonyl, CVCV alkylcarbonyl 174 200932732, c6-c1()-arylcarbonyl, c6 -c10-aryl-crc8-alkylcarbonyl, CrC6-alkylcarboxy, C6-C1()-arylcarboxy, CVCV alkylthiol, C6-C1 (rarylthio), CrC6-alkyl Mercaptocarbonyl, C3-C8-cycloalkylfluorenylcarbonyl, C6-C1()-aryldecylcarbonyl, CVCV alkylmercaptocarboxy 5, C6-C1()-aryldecylcarboxy, Q-CV alkane Sulfosyl, C6-C10-arylsulfonyl, CrC6-alkyloxythio, C6-C1()-aryloxythio, each of which is optionally substituted one or more times by :crc6-alkyl, Ci-CV alkoxy, c6-c1 (r aryloxy, co2h, so3h, ® amine, CVCV alkylamino, bis-CVC6-alkylamino, sulfhydryl, 10 Merid, cyano, cyano, fluoro, chloro, thio, oxime, CF3 or OCF3; • co2h; so3h; amine; 15 substituted by a residue selected from the group below or Multiple amino groups: crc6-alkyl, C6-C1()-aryl, C6-C10-aryl-Q-C6-alkyl, Crc6-alkylcarbonyl, C6-C1 (r arylcarbonyl , CrC6-alkylsulfonyl and C6_CiQ-aryl base; a disubstituted amino group of the following formula (II): -NW 20 °(11) wherein 〇 represents 0 or 1, and W represents oxygen , CH 2 or NR 6 , R 6 is selected from the group consisting of hydrogen and C! -C 6 -alkyl, and the methylene group of the formula (II) thereof may be optionally substituted by a crc 6-alkyl group, a fluoro group or a chloro group. Secondary; 175 200932732 conh2 ; so2nh2 ; conh2 or so2nh2, wherein the amino functionality is selected from the group consisting of crc6-alkyl, C6-C1 (r aryl or C6-C1 (r-aryl group of r aryl-CrCV alkyl) Substituting one or more times, and in the case of an amine functional group substituted with a di-c^-cv alkyl group, the alkyl residue may be bonded to form a 5 or 6 membered ring; a sulfhydryl group; a hydroxyl group; ❹ 10 nitro; cyano; 1 gas-based base, - halogen selected from fluoro, chloro, molybdenum or halo; CF3; 15 OCF3; or a saturation consisting of up to 10 atoms An unsaturated or aromatic heterocyclic ring system which is optionally substituted one or more times by: CrQ-alkyl, CkCV alkoxy, COOH, S03H, amine, sulfhydryl, Base, fluorenyl, cyano, fluoro, chloro, dimethyl 20, iodo, CF3 or OCF3; η and m are 0; and Y is phenyl substituted by one or more of the following Sub: CrC6-alkyl; phenyl; Q-CV alkoxy; hydroxy; fluoro; chloro; bromo; CF3; OCF3; amine; or alternatively substituted by CrC6-alkyl 176 200932732 One or two times of CONH2, wherein the selective CVCV alkyl residues can be combined to form a 5 or 6 membered ring; or a stereoisomer thereof, a pharmaceutically acceptable salt or ester or a prodrug. 5 60 10 15 60. The compound of any one of claims 57 to 59, wherein Y is a phenyl group substituted by one or more of the following: CVQ-alkyl; phenyl; Ci_C6_Oxygen Base; fluoro group; chloro group; moiety group; CF3; OCF3; amine group; or CONH2 which is optionally substituted by Q-C6-alkyl one or two times, wherein the selective CVCV The alkyl residues can be combined to form a 5 or 6 membered ring. 61. The compound of claim 60, wherein Y is a phenyl group substituted one or two times with a hydroxy, fluoro, chloro or bromo group. 62. The compound of claim 60, wherein Y is phenyl, which is substituted at the 4-position with a fluoro or by a gas group, at the 2- and 4-positions by a fluoro group, at 2- Substitution with a 4-position by a chloro group or a 4-position by a phenyl group. 63. A compound of formula (I):

其中 R1至R5係彼此獨立地代表：氫； 177 200932732 Ci_C6_ 烧基、C3-C8_ 環烧基、C6_Ci〇-芳基、C6-Ci〇-芳基-CrCV烷基、CVCV烷氧基、c6-c1()-芳氧基、 C6-Ci〇-芳基-Ci_C8·烧氧基、Ci_C6_烧氧基幾基、C6-Ci〇_ 芳氧基羰基、c6-c1()-芳基-CrCs-烷氧基羰基、crc6-烷 5 基羰基、c6-c1()-芳基羰基、c6-c1()-芳基-crc8-烷基羰基、crc6-烷基羧基、c6-c1()-芳基羧基、crc6-烷基氫硫基、C6-C1()-芳基氫硫基、CrCV烷基Μ基羰基、 C3-C8-環烷基巯基羰基、C6-C1()-芳基Μ基羰基、CVCV 烷基酼基羧基、C6-C1G-芳基Μ基羧基、CrC6-烷基磺醯 10 基、C6-Ci〇-方基績酿基、Ci_C6-烧基氧硫基、C6-Ci〇-方基氧硫基，其中各者選擇性地被下列各者取代一次或多次： CVCV烷基；crc6-烷氧基；c6-c1()-芳氧基； co2h ； so3h ； CONH2 ； SO2NH2 ； CONH2 或 so2nh2，其中該胺基官能度被選自crc6-烷基、 15 C6-C1()-芳基或C6-C1()-芳基-CVQ-烷基的殘基取代一次或多次，及其中在一種經二-CrCV烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：Ci_C6-烧基、C6_Ci。-芳基、C6_Ci〇-芳基-C1-C4-20 烷基、CVCV烷基羰基、C6-C1()-芳基羰基、Ci-CV烷基磺醯基及c6-c1(r芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氯代基：漠代基；換代基；CF3 或 OCF3 ; co2H; 200932732 5 so3h ; 胺基；經選自下列群中的殘基取代一或多次之胺基： Ci-C6-烧基、C6-Ci〇-方基、C6~Ci〇-芳基-Ci-Cf 烧基、 CrC6-烷基羰基、C6-C1()-芳基羰基、Q-C6-烷基磺醯基及C6-Ci〇-芳基績酿基，具下列化學式（II)之一種經二取代的胺基： Ο ί~\ —N W Η7] ° (Π) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選 10 自氫與Q-CV烷基，及其中化學式(II)中的亞甲基可選擇性地被Q-C6-烷基、氟代基或氣代基取代一或二次； conh2 ; so2nh2 ； CONH2或S02NH2，其中該胺基官能度被選自 15 φ CrC6-烷基、C6-C1()-芳基或C6-C1(r芳基-(VC6-烷基的殘基取代一次或多次，及其中在一種經二-Ci-CV烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或 6員環；硫氫基； 20 羥基；硝基；氰基；氣績酿基； 179 200932732 選自氟代基、氣代基、溴代基或碘代基之ii素； cf3 ； OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族 5 雜環式環系統，其選擇性地被下列各者取代一或多次： CrC6-烷基；Ci-Ce-烷氧基；COOH ; S03H ; conh2 ; so2nh2 ; conh2或so2nh2，其中該胺基官能度被選自CkCV烷基、c6-c1()-芳基或c6-c1(r芳基 -Ci-Cr烷基的殘基取代一次或多次：及其中在一種 10 經二-CVCV烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一或多次之胺基：CkCV烷基、C6-C10-芳基、C6-C1(r芳基-CrCV烷基、CrC6-烷基羰基、 C6-C10-芳基羰基、Q-Q-烷基磺醯基及C6-C1(r芳基磺 15 醯基；硫氫基；羥基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；CF3或OCF3 ; 及其中R1至R5中之任二或多者可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統； η代表0 ; m代表1 ; 20 Y代表選擇性地被下列各者取代一或多次之苯基： a)Ci_C6_烧基、C6_Ci〇-芳基、C6-Ci〇-芳基-Ci_C8-烧基、CrC6-烷氧基、C6-C10-芳氧基、C6-C10-芳基-Q-CV 烷氧基、CVC6-烷氧基羰基、C6-C1()-芳氧基羰基、 C6-C1(r芳基-CrC8-烷氧基羰基、Q-CV烷基羰基、 200932732 C6-C1()-芳基羰基、C6-C1Q-芳基-CrC8-烷基羰基、CrCV 烷基羧基、c6-c10-芳基羧基、crc6-烷基氫硫基、 c6-c1()-芳基氫硫基、crc6-烷基巯基羰基、c3-c8-環烷基巯基羰基、C6-C1G-芳基巯基羰基、CVCV烷基酼基羧 5 基、C6-Ci〇-^•基疏基叛基、Ci-Cf烧基績酿基、C6-Ci〇_ 芳基磺醯基、crc6-烷基氧硫基、c6-c10-芳基氧硫基；其中各者選擇性地被下列各者取代一或多次： Cj-CV烷基；CrCV烷氧基；選擇性地被crc6-烷基 ® 取代一或二次之conh2或so2nh2 ; so3h ; co2h ; 10 胺基；經選自下列群中的殘基取代一或多次之胺基：CVC6-烷基、C6-C10-芳基、C6-C10-芳基-CrC4-烷 • 基、CrCV烷基羰基、c6-c1()-芳基羰基、Q-cv烷基績酿基及C6-C ι〇-方基確酿基，硫風基，輕基，石肖基；氰基；氟代基；氯代基；溴代基；碘代基；cf3 15 或 OCF3 ; 其中該等選擇性取代基中之數者可結合而形成稠翁合的飽和、不飽和或芳族同環或雜環系統；或 b) 一種由至多10個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多 20 次：CkCV烷基；Q-CV烷氧基；COOH ;選擇性地被 crc6-烷基取代一或二次之CONH2或S02NH2 ; S03H ; 胺基；經選自下列群中的殘基取代一或多次之胺基： Ci-C6-烧基、C^-Cio-方基、C6-Ci〇-芳基-C1-C4-烧基、 CrC6-烷基羰基、C6-C1(r芳基羰基、CVCV烷基磺醯基 181 200932732 AC6-C1(r芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；cf3或ocf3 ;或 c)羥基；硫氫基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；cf3 ; ocf3 ; co2h ; S03H ; CONH2 ; S02NH2 ; C0NH2*S02NH2，其中該胺基官能度被選自Ci_C6_烧基、C6-Ci〇-芳基或C6-Ci〇-芳基-C1-C4- 烷基的殘基取代一次或多次，及其中在一種經二-crc6- 烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的殘基取代一 © 或多次之胺基：crc6-烷基、c6-c10-芳基' C6-C10-芳基 -CrCs-烷基、CrC6-烷基羰基、c6-c10-芳基羰基、 — Ci-CV烧基績醯基及C6-C10-芳基確醯基；具下列化學式 - (IV)之一種經二取代的胺基： Γ~\ —N w 'Η/] ° (IV) 其中〇代表0或1 ’而W代表氧、CH2或NR6，R6係選自氫與C1-C4-烧基，及其中化學式(iv)中的亞甲基可選 ❹ 擇性地被CrCV烷基、氟代基或氣代基取代一或二次；前提在於Y並非代表未經取代的苯基，若Ri、R2及 R5代表氫，R4代表氫、三氟曱氧基、三氟丁氧基、 3,3,5,5-四甲基環己氧基、苄氧基、苯氧基、苯基、2_ 二甲基胺基乙氧基或3-曱基苯氧基-甲基，及R3代表氫、二氟甲氧基、三氟丁氧基、3,3,5,5-四甲基環己氧基、苯氧基、4-氣苯氧基、環己基、苯基、嗎啉磺酿基、 182 200932732 3,3,5-三曱基環己基胺基磺醯基、2,2,6,6-四甲基哌啶-4-基胺基磺醯基、2-(二異丙基胺基乙基）胺基磺醯基、4-甲基哌嗪-1-基-磺醯基、3,3-二甲基哌啶羰基或3,5-二氯苯氧基、2-二甲基胺基乙氧基或3-甲基苯氧基-曱基。 5 64.如申請專利範圍第63項之化合物，其中R1至R5係彼此獨Wherein R1 to R5 are independently of each other: hydrogen; 177 200932732 Ci_C6_ alkyl, C3-C8_ cycloalkyl, C6_Ci〇-aryl, C6-Ci〇-aryl-CrCV alkyl, CVCV alkoxy, c6- C1()-aryloxy, C6-Ci〇-aryl-Ci_C8·alkoxy, Ci_C6_alkoxy, C6-Ci〇_ aryloxycarbonyl, c6-c1()-aryl-CrCs - alkoxycarbonyl, crc6-alkyl-5 carbonyl, c6-c1()-arylcarbonyl, c6-c1()-aryl-crc8-alkylcarbonyl, crc6-alkylcarboxy, c6-c1()- Arylcarboxy, crc6-alkylthiol, C6-C1()-arylthiothio, CrCV alkylmercaptocarbonyl, C3-C8-cycloalkylfluorenylcarbonyl, C6-C1()-arylhydrazine Carbonyl group, CVCV alkyl decyl carboxyl group, C6-C1G-aryl decyl carboxyl group, CrC6-alkylsulfonyl 10 group, C6-Ci〇-aryl base group, Ci_C6-alkylthio group, C6-Ci〇 a aryloxythio group, each of which is optionally substituted one or more times by: CVCV alkyl; crc6-alkoxy; c6-c1()-aryloxy; co2h; so3h; CONH2; SO2NH2 ; CONH2 or so2nh2, wherein the amino functionality is selected from the group consisting of crc6-alkyl, 15 C6-C1()-aryl or C6-C1()-aryl-CVQ-alkyl Substituting one or more times, and in the case of an amine functionality substituted with a di-CrCV alkyl group, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; selected from the group consisting of The residue in the group is substituted with one or more amine groups: Ci_C6-alkyl, C6_Ci. -aryl, C6_Ci〇-aryl-C1-C4-20 alkyl, CVCV alkylcarbonyl, C6-C1()-arylcarbonyl, Ci-CV alkylsulfonyl and c6-c1 (rarylsulfonate) Sulfhydryl; sulfhydryl; hydroxy; nitro; cyano; fluoro; chloro: molybdenum; substituted group; CF3 or OCF3; co2H; 200932732 5 so3h; amine group; One or more amino groups substituted by a residue: Ci-C6-alkyl, C6-Ci〇-square, C6~Ci〇-aryl-Ci-Cf alkyl, CrC6-alkylcarbonyl, C6-C1 ( )-arylcarbonyl, Q-C6-alkylsulfonyl and C6-Ci〇-aryl, a disubstituted amino group of the following formula (II): Ο ί~\ —NW Η7] ° (Π) where 〇 represents 0 or 1, and W represents oxygen, CH2 or NR6, R6 is selected from 10 hydrogen and Q-CV alkyl, and the methylene group in formula (II) is optionally Q -C6-alkyl, fluoro or ke group substituted one or two times; conh2; so2nh2; CONH2 or S02NH2, wherein the amine functionality is selected from 15 φ CrC6-alkyl, C6-C1()-aryl Or a C6-C1 (raryl-(VC6-alkyl residue substituted one or more times, and an amine substituted with a di-Ci-CV alkyl group) In the case of functionality, the alkyl residue may combine to form a 5 or 6 membered ring; sulfhydryl; 20 hydroxy; nitro; cyano; gas-based; 179 200932732 selected from fluoro, alkoxy a bromo or iodo group; cf3; OCF3; or a saturated, unsaturated or aromatic 5-heterocyclic ring system consisting of up to 10 atoms, optionally substituted by one or the following Multiple times: CrC6-alkyl; Ci-Ce-alkoxy; COOH; S03H; conh2; so2nh2; conh2 or so2nh2, wherein the amine functionality is selected from CkCV alkyl, c6-c1()-aryl or Substituting c6-c1 (r-aryl-Ci-Cr alkyl group for one or more substitutions: and in the case of an amine functional group substituted with a di-CVCV alkyl group, the alkyl residue may be bonded And forming a 5 or 6 membered ring; an amine group; one or more amine groups substituted with a residue selected from the group consisting of CkCV alkyl, C6-C10-aryl, C6-C1 (r-aryl-CrCV alkane) ,CrC6-alkylcarbonyl, C6-C10-arylcarbonyl, QQ-alkylsulfonyl and C6-C1 (rarylsulfonyl 15 fluorenyl; hydroxy; hydroxy; nitro; cyano; fluoro Chloride; bromine ; iodo group; CF3 or OCF3; and any two or more of R1 to R5 thereof may be combined to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; η represents 0; m represents 1; 20 Y represents a phenyl group which is optionally substituted by one or more of the following: a) Ci_C6_alkyl, C6_Ci〇-aryl, C6-Ci〇-aryl-Ci_C8-alkyl, CrC6-alkoxy , C6-C10-aryloxy, C6-C10-aryl-Q-CV alkoxy, CVC6-alkoxycarbonyl, C6-C1()-aryloxycarbonyl, C6-C1(r-aryl-CrC8 - alkoxycarbonyl, Q-CV alkylcarbonyl, 200932732 C6-C1()-arylcarbonyl, C6-C1Q-aryl-CrC8-alkylcarbonyl, CrCV alkylcarboxy, c6-c10-arylcarboxy, Crc6-alkyl thiol group, c6-c1()-arylhydrothio group, crc6-alkylmercaptocarbonyl, c3-c8-cycloalkylfluorenylcarbonyl, C6-C1G-aryldecylcarbonyl, CVCV alkyl hydrazine Carboxylic acid 5 group, C6-Ci〇-^• thiol base, Ci-Cf alkyl base, C6-Ci〇_ arylsulfonyl, crc6-alkyl oxythio, c6-c10- Aryloxythio; each of which is optionally substituted one or more times by: Cj-CV alkyl; CrCV alkoxy; optionally by crc6- Substituting one or two conh2 or so2nh2; so3h; co2h; 10 amine; an amine group substituted one or more times with a residue selected from the group consisting of CVC6-alkyl, C6-C10-aryl, C6-C10-aryl-CrC4-alkanyl group, CrCV alkylcarbonyl group, c6-c1()-arylcarbonyl group, Q-cv alkyl group and C6-C ι〇-square base, sulfur Wind-based, light-based, stone-based; cyano; fluoro; chloro; bromo; iodo; cf3 15 or OCF3; wherein the number of such selective substituents can be combined to form a thick a saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; or b) a saturated, unsaturated or aromatic heterocyclic ring system consisting of up to 10 atoms, optionally substituted by one or the following 20 more times: CkCV alkyl; Q-CV alkoxy; COOH; CONH2 or S02NH2 which is optionally substituted by crc6-alkyl one or two times; S03H; amine group; substituted by a residue selected from the following group One or more amine groups: Ci-C6-alkyl, C^-Cio-square, C6-Ci〇-aryl-C1-C4-alkyl, CrC6-alkylcarbonyl, C6-C1 (r-aryl) Alkylcarbonyl, CVCV alkylsulfonyl 181 200932732 AC 6-C1(rarylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; chloro; bromo; iodo; cf3 or ocf3; or c) hydroxy; Nitro; cyano; fluoro; ketone; bromo; iodo; cf3; ocf3; co2h; S03H; CONH2; S02NH2; C0NH2*S02NH2, wherein the amine functionality is selected from Ci_C6 Substituting one or more residues of a calcinyl group, a C6-Ci〇-aryl group or a C6-Ci〇-aryl-C1-C4-alkyl group, and an amine group substituted with a di-crc6-alkyl group In the case of functionality, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; one or more amine groups substituted with a residue selected from the group consisting of: crc6-alkyl, c6- C10-aryl 'C6-C10-aryl-CrCs-alkyl, CrC6-alkylcarbonyl, c6-c10-arylcarbonyl, —Ci-CV alkyl and C6-C10-aryl a disubstituted amino group of the formula - (IV): Γ~\ —N w 'Η/] ° (IV) where 〇 represents 0 or 1 ' and W represents oxygen, CH 2 or NR 6 , R 6 is selected From hydrogen to a C1-C4-alkyl group, and the methylene group in the chemical formula (iv) is optionally selected The CrCV alkyl, fluoro or ke group is substituted one or two times; provided that Y does not represent an unsubstituted phenyl group, and if Ri, R2 and R5 represent hydrogen, R4 represents hydrogen, trifluoromethoxy, trifluoro Butoxy, 3,3,5,5-tetramethylcyclohexyloxy, benzyloxy, phenoxy, phenyl, 2-dimethylaminoethoxy or 3-mercaptophenoxy-methyl And R3 represent hydrogen, difluoromethoxy, trifluorobutoxy, 3,3,5,5-tetramethylcyclohexyloxy, phenoxy, 4-cyclophenoxy, cyclohexyl, benzene Base, morpholine sulfonate, 182 200932732 3,3,5-trimethylcyclohexylaminosulfonyl, 2,2,6,6-tetramethylpiperidin-4-ylaminosulfonyl, 2-(Diisopropylaminoethyl)aminosulfonyl, 4-methylpiperazin-1-yl-sulfonyl, 3,3-dimethylpiperidinylcarbonyl or 3,5-dichloro Phenoxy, 2-dimethylaminoethoxy or 3-methylphenoxy-fluorenyl. 5 64. The compound of claim 63, wherein R1 to R5 are independent of each other

10 1510 15

20 立地代表：氫；羥基； crc6-烷基、c6-c1()-芳基、crc6-烷氧基、c6-c10-芳氧基、C6-C1()-芳基-CkCV烷氧基、crc6-烷基羧基、 c6-c1()-芳基羧基、crc6-烷基磺醯基、c6-c1()-芳基磺醯基，其中各者選擇性地被下列各者取代一次或多次： Ci_C6_烧基、Ci-C6-烧氧基、胺基、Ci_C6-烧基胺基、二-Ci_C6_烧基胺基、象基、說代基、氯代基、>臭代基、氰基、CF3或OCF3 ; 胺基；經選自crc6-烷基、c6-c1(r芳基的殘基取代一或多次之胺基； 1-吡咯基、2-吡咯基或3-吡咯基，其選擇性地被一或多個選自crc6-烷基、胺基、氟代基、氣代基或cf3 之殘基取代；具下列化學式(II)之一種經二取代的胺基：20 Site representative: hydrogen; hydroxyl; crc6-alkyl, c6-c1()-aryl, crc6-alkoxy, c6-c10-aryloxy, C6-C1()-aryl-CkCV alkoxy, Crc6-alkylcarboxy, c6-c1()-arylcarboxy, crc6-alkylsulfonyl, c6-c1()-arylsulfonyl, each of which is optionally substituted one or more times by Secondary: Ci_C6_alkyl, Ci-C6-alkoxy, amine, Ci_C6-alkylamino, bis-Ci_C6-alkylamino, azo, hydrazino, chloro, > odoryl , cyano, CF3 or OCF3; an amine group; an amine group substituted one or more times selected from the group consisting of crc6-alkyl, c6-c1 (r-aryl group; 1-pyrrolyl, 2-pyrrolyl or 3- a pyrrolyl group which is optionally substituted by one or more residues selected from the group consisting of a crc6-alkyl group, an amine group, a fluoro group, a carbyl group or a cf3; a disubstituted amino group having the following formula (II) :

183 200932732 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-C6-烷基，及其中化學式(II)中的亞甲基可選擇性地被CrC6-烷基、氟代基或氣代基取代一或二次； conh2 ; 5 S02NH2 ; CONH2或S02NH2，其中該胺基官能度被選自 crc6-烷基或C6-C1G-芳基的殘基取代一或二次；氟代基；氯代基； 10 溴代基； CF3 ;或 OCF3。 65.如申請專利範圍第63或64項之化合物，其中R1至R5中之一或多者代表氫、氟或氯。 15 66.如申請專利範圍第65項之化合物，其中R1或R5代表氫或氟。 67.如申請專利範圍第63至66項中任一項之化合物，其中R1 至R5中之一或多者代表羥基；或 CrC6-烷氧基、C6-C10-芳氧基、C6-C10-芳基-CVCV 烷氧基、CVC6-烷基羧基、C6-C1(r芳基羧基、CrC6-烷 20 基磺醯基、C6-C1(r芳基磺醯基，其中各者選擇性地被下列各者取代一次或多次：CVC6-烷基、Q-CV烷氧基、胺基、Q-C6-烷基胺基、二-CVC6-烷基胺基、選擇性地被C rCV烷基或C6-C!。-芳基取代一或二次之CONH2或 so2nh2、羥基、氟代基、氣代基、溴代基、氰基、 200932732 5 CF3 或 OCF3。 68.如申請專利範圍第67項之化合物，其中R2、R3或R4中之一者代表羥基；或 CrC6-烷氧基、C6-C10-芳氧基或C6-C10-芳基-CrC6-烷氧基，其中各者選擇性地被下列各者取代一或多次： OCV烷基、CVCV烷氧基、胺基、CkCV烷基胺基、二-CrC6-烷基胺基、選擇性地被CVCV烷基或c6-c10-芳基取代一或二次之conh2或so2nh2、羥基、氟代基、氯代基或漠代基。 10 69.如申請專利範圍第63至68項中任一項之化合物，其中R1 至R5中之一或多者代表胺基；經選自Q-C6-烷基、C6-C10-芳基的殘基取代一或多次之胺基；或具下列化學式(II)之一種經二取代的胺基： 15 Q —N W °(11) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與Q-C6-烷基，及其中化學式(II)中的亞甲基可選擇性地被Q-CV烷基、氟代基或氣代基取代一或二次。 70.如申請專利範圍第69項之化合物，其中R2、R3或R4代表 20 胺基；被選自CrC6-烷基、C6-C1(r芳基的殘基取代一或二次之胺基；或具下列化學式(II)之一種經二取代的胺基： 185 ° (II) 200932732183 200932732 wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and Q-C 6 -alkyl, and the methylene group in formula (II) is optionally CrC6-alkane Substituting one or two groups with a fluoro, or fluoro group; conh2; 5 S02NH2; CONH2 or S02NH2, wherein the amino functionality is replaced by a residue selected from the group consisting of a crc6-alkyl or a C6-C1G-aryl group. Secondary; fluoro; chloro; 10 bromo; CF3; or OCF3. 65. A compound according to claim 63 or 64, wherein one or more of R1 to R5 represents hydrogen, fluorine or chlorine. 15 66. The compound of claim 65, wherein R1 or R5 represents hydrogen or fluorine. The compound according to any one of claims 63 to 66, wherein one or more of R1 to R5 represents a hydroxyl group; or a CrC6-alkoxy group, a C6-C10-aryloxy group, a C6-C10- group aryl-CVCV alkoxy, CVC6-alkylcarboxy, C6-C1 (rarylcarboxy, CrC6-alkanylsulfonyl, C6-C1 (rarylsulfonyl), each of which is selectively One or more of the following: CVC6-alkyl, Q-CV alkoxy, amine, Q-C6-alkylamino, bis-CVC6-alkylamino, optionally CrCV alkyl Or C6-C!--aryl substituted one or two times of CONH2 or so2nh2, hydroxy, fluoro, carbyl, bromo, cyano, 200932732 5 CF3 or OCF3. 68. a compound wherein one of R2, R3 or R4 represents a hydroxyl group; or a CrC6-alkoxy group, a C6-C10-aryloxy group or a C6-C10-aryl-CrC6-alkoxy group, each of which is selective Substituted one or more times by: OCV alkyl, CVCV alkoxy, amine, CkCV alkylamino, di-CrC6-alkylamine, optionally CVCV alkyl or c6-c10- The aryl group replaces one or two conh2 or so2nh2, hydroxyl, fluoro group The compound of any one of clauses 63 to 68, wherein one or more of R1 to R5 represents an amine group; and is selected from a Q-C6-alkyl group. a C6-C10-aryl residue substituted with one or more amine groups; or a disubstituted amino group of the following formula (II): 15 Q - NW ° (11) wherein 〇 represents 0 or 1, Wherein W represents oxygen, CH2 or NR6, and R6 is selected from the group consisting of hydrogen and Q-C6-alkyl, and wherein the methylene group in the formula (II) is optionally substituted by Q-CV alkyl, fluoro or gas Substituting one or two. 70. A compound according to claim 69, wherein R 2 , R 3 or R 4 represents 20 amino groups; and is substituted by a residue selected from the group consisting of CrC 6-alkyl and C 6-C 1 (r aryl) Or a secondary amine group; or a disubstituted amino group of the following formula (II): 185 ° (II) 200932732

5 10 15 其中〇代表0或1，而w代表氧、CH2或NR6，R6係選自氫與CrC6-烷基’及其中化學式(11)中的亞曱基可選擇性地被q-C6-烷基、氟代基或氣代基取代一或二次。 71.如申請專利範圍第63至70項中任一項之化合物，其中γ 代表被下列各者取代一或多次之苯基： aA-CV烧基、CVC1()-芳基、Q-Q。-芳基-CrC6-烧基、cvcv烧氧基、c6_Cl0_芳氧基、C6_Cl0_芳基_Ci_C6_ 烧氧基’其中各者選擇性地被下列各者取代一次或多 -人.Ci-C6-院基，Ci-C6_烧氧基，so3h ; C02H ;胺基；經選自下列群中的殘基取代一或多次之胺基： Ci-C6-炫《基、c6-C1()-芳基、C6-Ci〇-芳基-CrC6-燒基、 Ci-CV烧基幾基、C6-C1(r芳基幾基、CVC；6-院基續瞳基及CVCht芳基確醯基；硫氫基；經基；確基；氰基；氣代基，氣代基； >臭代基；峨代基；CF3 ; cONHg ; so2nh2; 0CF3;或其中該胺基官能度被(^-(：6_烷基取代一次或二次之CONH2或S02NH2 ; 或被：5 10 15 wherein 〇 represents 0 or 1, and w represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and CrC 6 -alkyl ' and the fluorenyl group in the formula (11) is optionally q-C6- The alkyl, fluoro or ke group is substituted one or two times. The compound according to any one of claims 63 to 70, wherein γ represents a phenyl group substituted by one or more of the following: aA-CV alkyl, CVC1()-aryl, Q-Q. - aryl-CrC6-alkyl, cvcv alkoxy, c6_Cl0_aryloxy, C6_Cl0_aryl_Ci_C6_ alkoxy" each of which is optionally substituted by one or more - human. Ci-C6 - affiliation, Ci-C6_alkoxy, so3h; C02H; amin; one or more amine groups substituted with a residue selected from the group consisting of: Ci-C6-Hyun", c6-C1() -aryl, C6-Ci〇-aryl-CrC6-alkyl, Ci-CV alkyl, C6-C1 (raryl), CVC; 6-institutional thiol and CVCht aryl Thiohydro group; thiol group; thiol group; gas group, gas group; > odor group; oxime group; CF3; cONHg; so2nh2; 0CF3; or wherein the amine functionality is ( ^-(:6_Alkyl substituted once or twice of CONH2 or S02NH2; or by:

b)羥基；硫氫基；硝基；氰基；氟代基；氣代 20 基；溴代基；碘代基；CF3 ; OCF3 ; C〇2H ; S03H ; conh2 ; so2nh2 ;或conh2*so2nh2，其中該胺基官能度被CVC6-烧基、C6-Ci〇-芳基、C6-C10-芳基_CrC6-烧基取代一次或二次，及其中在一種經二-Ci-Ce-烷基取代 186 200932732 5 的胺基官能度之情況下，該烷基殘基可結合而形成5或6 員環；胺基；被心/^烷基或苯基取代一或多次之胺基；具下列化學式(II)之一種經二取代的胺基： ί~\ —Ν W Η7] °(Π) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與q-cv烷基，及其中化學式(II)中的亞甲基可選擇 ❹ 性地被CVCV烷基、氟代基或氣代基取代一或二次；或被： c) 一種由至多10個原子組成之飽和、不飽和或芳 10 族雜環式環系統，其選擇性地被下列各者取代一或多次：CVCV烷基；CrC6-烷氧基；COOH ; conh2 ; S02NH2 ;其中該胺基官能度被CVCV烷基取代一次或二次之CONH2或S02NH2，其中該CrCV烷基可結合而形成5或6員環；S03H ;胺基；經選自下列群中的殘基取 15 代’一或多次之胺基.Ci_C6-烧基、C6_Ci〇-芳基、C6-Ci〇-方基-Ci-C6-烧基、Ci-CV烧基幾基、CVCio-芳基幾基、 Q-CV烷基磺醯基及C6-C1G-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基；碘代基；cf3 ;或〇cf3。 20 72.如申請專利範圍第71項之化合物，其中γ為被下列各者取代一或多次之苯基：CrC6-烷基；苯基；CrC6-烷氧基；羥基；氟代基；氣代基；溴代基；CF3 ; OCF3 ;胺基；選擇性地被crc6-烷基取代一或二次之conh2，其中該等 187 200932732 選擇性的CrC6-烷基殘基可結合而形成5或6員環。 73. 如申請專利範圍第71項之化合物，其中γ係被羥基、氟代基、氯代基或溴代基取代一或二次之苯基。 74. 如申請專利範圍第72項之化合物，其中Y為苯基，其在 4-位置被氟代基或被氣代基取代、在2-與4-位置被氟代基取代、在2-與4-位置被氣代基取代或在4-位置被苯基取代。 75. 如申請專利範圍第63項之化合物，其中γ係被氟代基、氣代基或溴代基取代一或二次之苯基；及R2至R4中之〇任一者代表OR7，其中R7係選自氫與CVC6-烷基。 76. 如申請專利範圍第75項之化合物，其中γ為苯基，其在 ' 4-位置被氟代基或被氣代基取代、在2-與4-位置被氟代 · 基取代或在2-與4-位置被氣代基取代。 77. 如申請專利範圍第75或76項之化合物，其中R1或r5代表氟或氫。 78. 如申請專利範圍第75至77項中任一項之化合物，其中R3 或者R3與R4代表羥基。 Q 79·—種化合物，其包括具下列子結構式(m)之一藥效基團：b) hydroxy; sulfhydryl; nitro; cyano; fluoro; gas 20; bromo; iodo; CF3; OCF3; C〇2H; S03H; conh2; so2nh2; or conh2*so2nh2, Wherein the amine functionality is substituted once or twice with CVC6-alkyl, C6-Ci〇-aryl, C6-C10-aryl-CrC6-alkyl, and in a di-Ci-Ce-alkyl group Substituting the amine functionality of 186 200932732 5, the alkyl residue may be combined to form a 5 or 6 membered ring; an amine group; an amine group substituted one or more times by a heart/alkyl group or a phenyl group; A disubstituted amino group of the following formula (II): ί~\ —Ν W Η7] °(Π) wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , and R 6 is selected from hydrogen and q- The cv alkyl group, and the methylene group of the formula (II) thereof, may be optionally substituted one or two times with a CVCV alkyl group, a fluoro group or a gas group; or by: c) one consisting of up to 10 atoms a saturated, unsaturated or aromatic 10 group heterocyclic ring system which is optionally substituted one or more times by: CVCV alkyl; CrC6-alkoxy; COOH; conh2; S02NH2; wherein the amine function Degree is taken by CVCV alkyl One or two times of CONH2 or S02NH2, wherein the CrCV alkyl group may be combined to form a 5 or 6 membered ring; S03H; an amine group; 15 or more 'one or more amine groups' are taken from a residue selected from the group below. Ci_C6-alkyl, C6_Ci〇-aryl, C6-Ci〇-square-Ci-C6-alkyl, Ci-CV alkyl, CVCio-aryl, Q-CV alkylsulfonyl and C6-C1G-arylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; thio; bromo; iodo; cf3; or 〇cf3. 20 72. The compound of claim 71, wherein γ is phenyl substituted by one or more of the following: CrC6-alkyl; phenyl; CrC6-alkoxy; hydroxy; fluoro; Substituent; bromo; CF3; OCF3; amine; optionally substituted by crc6-alkyl one or two conh2, wherein the 187 200932732 selective CrC6-alkyl residue can be combined to form 5 or 6-member ring. 73. A compound according to claim 71, wherein the gamma is substituted by a hydroxy, fluoro, chloro or bromo group for one or two phenyl groups. 74. The compound of claim 72, wherein Y is phenyl, which is substituted at the 4-position with a fluoro or by a gas group, at the 2- and 4-positions by a fluoro group, at 2- Substitution with a 4-position by an alkenyl group or a 4-position by a phenyl group. 75. A compound according to claim 63, wherein the γ is substituted by a fluoro group, an oxyl group or a bromo group for one or two phenyl groups; and any one of R2 to R4 represents OR7, wherein R7 is selected from the group consisting of hydrogen and CVC6-alkyl. 76. The compound of claim 75, wherein γ is phenyl, which is substituted at the 4-position by a fluoro group or by a gas group, at the 2- and 4-positions by a fluoro- group or The 2- and 4-positions are replaced by an angio group. 77. A compound according to claim 75 or 76, wherein R1 or r5 represents fluorine or hydrogen. The compound of any one of clauses 75 to 77, wherein R3 or R3 and R4 represent a hydroxyl group. Q 79 - a compound comprising a pharmacophore having one of the following substructures (m):

(III) 以用於抑制脂肪酸醯胺水解酶(FAAH)。 8〇. 一種藥學組成物，其包括如申請專利範圍第24至79項中 188 200932732 任一項之一化合物及一種藥學上可接受的載劑。 81. 如申請專利範圍第24至79項中任一項之化合物，用於作為一藥物。 5 Φ 10 曹 15 82. 如申請專利範圍第24至78項中任一項之化合物，用於抑制脂肪酸醢胺水解酶(FAAH)。 83. 如申請專利範圍第24至79項中任一項之化合物，用於治療因脂肪酸醯胺水解酶(FAAH)抑制作用而受到正面影響之一病症。 84. 如申請專利範圍第83項之化合物，其中該病症係選自疼痛；暈眩、σ區吐及噁心；飲食失調病症；神經與精神病變；急性與慢性神經退化性疾病；癲癇症；睡眠障礙；心血管疾病；癌症；免疫系統病症；寄生蟲、病毒或細菌性傳染病；炎性疾病；骨質疏鬆症；眼部病況；肺部病況及胃腸疾病。 85. 如申請專利範圍第24至79項中任一項之化合物，用於抑制脂肪酸醯胺水解酶(FAAH)之用途。 86. 如申請專利範圍第24至79項中任一項之化合物，用於治療因FAAH抑制作用而受到正面影響的一病症之用途。 87. —種具下列子結構式(III)之一藥效基團：(III) for inhibiting fatty acid indoleamine hydrolase (FAAH). A pharmaceutical composition comprising a compound of any one of 188, 2009, 327, 32, and a pharmaceutically acceptable carrier. 81. A compound according to any one of claims 24 to 79, for use as a medicament. 5 Φ 10 Cao 15 82. A compound according to any one of claims 24 to 78 for use in inhibiting fatty acid indoleamine hydrolase (FAAH). 83. A compound according to any one of claims 24 to 79 for use in the treatment of a condition which is positively affected by the inhibition of fatty acid indoleamine hydrolase (FAAH). 84. The compound of claim 83, wherein the condition is selected from the group consisting of pain; dizziness, sputum vomiting and nausea; eating disorders; neurological and psychiatric disorders; acute and chronic neurodegenerative diseases; epilepsy; Obstacle; cardiovascular disease; cancer; immune system disorders; parasitic, viral or bacterial infectious diseases; inflammatory diseases; osteoporosis; ocular conditions; pulmonary conditions and gastrointestinal diseases. 85. The use of a compound according to any one of claims 24 to 79 for inhibiting fatty acid indoleamine hydrolase (FAAH). 86. A compound according to any one of claims 24 to 79 for use in the treatment of a condition which is positively affected by FAAH inhibition. 87. — A pharmacophore with one of the following substructures (III):

(III) 用於製備一化合物之用途，該化合物係用於治療因 189 200932732 脂肪酸醯胺水解酶(FAAH)抑制作用而受到正面影響的一病症。 88. 如申請專利範圍第86或87項之用途，其中該病症係選自疼痛；暈眩、嘔吐及噁心；飲食失調病症；神經與精神 5 病變；急性與慢性神經退化性疾病；瘤癇症；睡眠障礙；心血管疾病；癌症；免疫系統病症；寄生蟲、病毒或細菌性傳染病；炎性疾病；骨質疏鬆症；眼部病況；肺部病況及胃腸疾病。(III) Use of a compound for the treatment of a condition which is positively affected by the inhibition of fatty acid indoleamine hydrolase (FAAH) by 189 200932732. 88. The use of claim 86 or 87, wherein the condition is selected from the group consisting of pain; dizziness, vomiting and nausea; eating disorders; neurological and psychiatric disorders; acute and chronic neurodegenerative diseases; ; sleep disorders; cardiovascular disease; cancer; immune system disorders; parasitic, viral or bacterial infectious diseases; inflammatory diseases; osteoporosis; ocular conditions; pulmonary conditions and gastrointestinal diseases.

89. —種用於製備如申請專利範圍第1至17項及第24至79項 10 中任一項的一化合物之方法，其中具化學式(IV)的一化合物：89. A method for the preparation of a compound of any one of claims 1 to 17 and 24 to 79, wherein a compound of formula (IV):

(IV) 其中(IV) where

15 R1至R5係彼此獨立地代表：氫； Ci-C6-烧基、C3-C8-環烧基、C6-CiQ-芳基、C6_Ci〇_ 芳基-CrCV烷基、CrCV烷氧基、c6-c1()-芳氧基、c6-c10-芳基-CkCV烷氧基、CrC6-烷氧基羰基、C6-Clcr芳氧基羰 20 基、C6-Clcr芳基-Q-C8-烷氧基羰基、CrC6-烷基羰基、 C6-C1()-芳基羰基、C6-C1()-芳基-CVC8-烷基羰基、Ci-CV 烷基羧基、c6-c1()-芳基羧基、CVCV烷基氫硫基、c6-c10- 190 20093273215 R1 to R5 are independently of each other: hydrogen; Ci-C6-alkyl, C3-C8-cycloalkyl, C6-CiQ-aryl, C6_Ci〇_ aryl-CrCV alkyl, CrCV alkoxy, c6 -c1()-aryloxy, c6-c10-aryl-CkCV alkoxy, CrC6-alkoxycarbonyl, C6-Clcr aryloxycarbonyl 20, C6-Clcr aryl-Q-C8-alkoxy Carbonyl group, CrC6-alkylcarbonyl group, C6-C1()-arylcarbonyl group, C6-C1()-aryl-CVC8-alkylcarbonyl group, Ci-CV alkylcarboxy group, c6-c1()-arylcarboxy group , CVCV alkyl thiol, c6-c10- 190 200932732

10 芳基氫硫基、crc6-烷基巯基羰基、c3-c8-環烷基酼基羰基、C6-C1()-芳基巯基羰基、CrCV烷基巯基羧基、 C6-C1()-芳基巯基羧基、CVCV烷基磺醯基、C6-C1()-芳基磺醯基、CkCV烷基氧硫基、C6-C1(r芳基氧硫基，其中各者選擇性地被下列各者取代一次或多次：CrC6-烷基、CVCV烷氧基、c6-c10-芳氧基、co2h、so3h、胺基、Ci-C6-烧基胺基、二-Ci_C6-烧基胺基、硫氮基、經基、硝基、氰基、氟代基、氯代基、>臭代基、蛾代基、 CF3 或 OCF3 ; co2h ； so3h ; 1510 aryl hydrosulfide, crc6-alkylmercaptocarbonyl, c3-c8-cycloalkylfluorenylcarbonyl, C6-C1()-aryldecylcarbonyl, CrCV alkyldecylcarboxy, C6-C1()-aryl Mercaptocarboxy group, CVCV alkylsulfonyl group, C6-C1()-arylsulfonyl group, CkCV alkyloxythio group, C6-C1 (raryloxythio group, each of which is selectively selected by the following Substituted one or more times: CrC6-alkyl, CVCV alkoxy, c6-c10-aryloxy, co2h, so3h, amine, Ci-C6-alkylamino, di-Ci_C6-alkylamino, sulfur Nitro, thio, nitro, cyano, fluoro, chloro, > odor, moth, CF3 or OCF3; co2h; so3h; 15

胺基；經選自下列群中的殘基取代一或多次之胺基： crc6-烷基、C6-C10-芳基、C6-C1()-芳基-CrCV烷基、 CVC6-烷基羰基、C6-C1()-芳基羰基、CkCV烷基磺醯基及C6_Ci〇-方基確酿基，具下列化學式(II)之一種經二取代的胺基： H7] L Jo (II) 其中〇代表0或1，而W代表氧、CH2或NR6，R6係選自氫與CrC6-烷基，及其中化學式(II)中的亞甲基可選擇性地被CVCV烷基、氟代基或氯代基取代一或二次； conh2 ; S02NH2 ; 191 20 200932732 CONH2或so2nh2，其中該胺基官能度被選自 Ci_C6-烧基、C6-Ci〇-芳基或C6-Ci〇-芳基-Ci_C6-烧基的殘基取代一或二次，及其中在一種經二-crc6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6 5 員環；硫氫基；羥基； *肖基；氰基； 10 氟績醯基；選自氟代基、氯代基、溴代基或碘代基之鹵素； cf3 ; OCF3 ;或一種由至多10個原子組成之飽和、不飽和或芳族 15 雜環式環系統，其選擇性地被下列各者取代一或多次： CVQ-烷基、Q-Q-烷氧基、COOH、S03H、胺基、硫氫基、經基、梢基、氰基、氟代基、氯代基、漠代基、碘代基、CF3或OCF3 ; 及其中R1至R5中之任二或多者可結合而形成稠合 20 的飽和、不飽和或芳族同環或雜環系統； m代表0、1、2、3、4、5或6; Y代表： a)氫； tOCVC^-烷基、單元不飽和或多元不飽和C2-C18- 200932732 亞烧基、C3-C8-環烷基、C6-C1(r芳基、c6-c1(r芳基 -CVCV烧基、CVCV烧氧基、c6_Ci()_芳氧基、c6_c10-芳基-Q-C8-烷氧基、CrC：6-烷氧基羰基、c6-C10-芳氧基羰基、CVCV芳基-CrQ-貌氧基羰基、Q-CV烧基戴基、C6-C1(r芳基羰基、c6-c10-芳基-CVCV烷基羰基、Crc6-烧基竣基、c6-c1(r芳基羧基、Q-CV炫基氫硫基、CVCnr芳基氫硫基、Cl_c6_烷基毓基羰基、 C3-Cs-環烷基巯基羰基、c6-C10-芳基巯基羰基、CVCV 烷基酼基羧基、C6-C1()-芳基巯基羧基、Ci-CV烷基磺酿基、C6-C10-芳基確醢基、q-CV院基氧硫基、 C6_C10-芳基氧硫基或一種由至多1〇個原子組成之飽和、不飽和或芳族雜環式環系統，其中各者選擇性地被下列各者取代一次或多次： bl)Ci_C6_ 烧基、C3-C8-環烧基、C6-Ci〇-芳基、 c6-c1(r芳基-CVCV烷基、CVCV烷氧基、c6-c1(r芳氧基、C6-CiQ-方基-C!-C8-烧氧基、Ci_C6_烧氧基I炭基、 c6-c1(r芳氧基羰基、CVCur芳基-Ci-Cs-烷氧基羰基、crc6-烷基羰基、C6-C1(r芳基羰基、C6-C1()-芳基 -Ci_C8-烧基幾基、Ci-C6-烧基叛基、C6-Ci〇-芳基叛基、CVCV烷基氫硫基、C6-C10-芳基氫硫基、Ci-CV 烷基巯基羰基、c3-c8-環烷基酼基羰基、c6-c1()-芳基疏基幾基、Ci-C6-炫基疏基竣基、C6-C1()-芳基疏基幾基、CrC6-烷基磺醯基、C6-C1()-芳基磺酿基、（VCV 烧基氧硫基、C6-CiQ-芳基氧疏基，其中各者選擇性 193 200932732 地被下列各者取代一次或多次：Ci-CV烷基；CVCV 烷氧基；CONH2 ; S02NH2 ;其中該胺基官能度被 (VC6-烷基取代一次或二次之CONH2或S02NH2 ; so3h ; co2h ;胺基；經選自下列群中的殘基取代一 5 或多次之胺基：CrCV烷基、C6-C10-芳基、C6-C10-芳基-CrC6-烷基、CrCV烷基羰基、C6-C1()-芳基羰基、 Cj-Ce-烷基磺醯基及C6-C1()-芳基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；CF3 ;或 OCF3 ; © 10 其中bl)中的數個取代基可結合而形成稠合的飽和、不飽和或芳族同環或雜環系統；或被：， b2)經基；硫氫基；硝基；氰基；氟代基；氯代基；溴代基；碘代基；CF3 ; C02H ; S03H ; OCF3 ; 15 conh2 ; so2nh2 ; conh2或so2nh2，其中該胺基官能度被選自crc6-烷基、c6-c1()-芳基或c6-c1()-芳基 ο -CrCV烷基的殘基取代一或二次，及其中在一種經二 ¥ -Q-C6-烷基取代的胺基官能度之情況下，該烷基殘基可結合而形成5或6員環；胺基；經選自下列群中的 20 殘基取代一或多次之胺基：CVCV烷基、c6-c10-芳基、c6-c1(r芳基-crc8-烷基、crc6-烷基羰基、 c6-c1()-芳基羰基、crc6-烷基磺醯基及c6-c1(r芳基磺醯基；或具下列化學式(II)之一種經二取代的胺基： 194 200932732 5 Ή7] °(ΙΙ) 其中0代表0或1、而W代表氧、CH2或NR6、R6係選自氫與crc6_烷基及其中化學式(II)中的亞甲基可選擇性地被取代一或二次：CrC6-烷基、氟代基或氯代基；或被： ❹ { b3)—種由至多1〇個原子組成之飽和、不飽和或芳族雜環式環系統，其選擇性地被下列各者取代一或多次：CVCV·烷基；CrC6-烷氧基；COOH ; CONH2 ; 10 S〇2NH2;其中該胺基官能度被crc6_烷基取代一次或二次之C0NHjS02NH2 ; S03H ;胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6-烷基、 C6-C1(r芳基、c6-C1()-芳基-CrC6-烧基、crc6-烧基戴基、C6-C10-芳基羰基、Q-Q-烷基磺醯基及c6-C10-芳 15 ❹ 基磺醯基；硫氫基；羥基；硝基；氰基；氟代基；氣代基；溴代基；破代基；CF3 ;或〇CF3 ; c)S〇3H ;胺基；經選自下列群中的殘基取代一或多次之胺基：CrC6-烷基、C6-C10-芳基、C6-Cl0-芳基 -CrC8-烷基、CVQ-烷基羰基、c6-C1(r芳基羰基、 20 CrCV烷基磺醯基及c6-C1(r芳基磺醯基；c〇NH2 ; S〇2NH2 ; conh2或so2nh2，其中該胺基官能度被選自 CrC6-烧基、C6-C1()-芳基或C6-C10-芳基-Ci-Cr烧基的殘基取代一次或二次，及其中在一種經二-^/^烷基取代 195 200932732 的胺基官能度之情況下，該烷基殘基可結合而形成5或6 員環；硫氫基；羥基；硝基；氰基；氟磺醯基；選自氟代基、氯代基、溴代基或碘代基之i素；CF3 ;或〇cf3 ; 5 環化形成一種呋二唑酮環系統，前提在於所製得的產物並非如申請專利範圍第24 項所排除之一化合物。 90.如申請專利範圍第89項之方法，其中形成呋二唑酮環系統之環化作用，係藉由碳醯氯、叛基二味°坐或一種碳酸 10 酯達成。Amine; one or more amine groups substituted with a residue selected from the group consisting of: crc6-alkyl, C6-C10-aryl, C6-C1()-aryl-CrCV alkyl, CVC6-alkyl Carbonyl, C6-C1()-arylcarbonyl, CkCV alkylsulfonyl and C6_Ci〇-aryl, a disubstituted amino group of the following formula (II): H7] L Jo (II) Wherein 〇 represents 0 or 1, and W represents oxygen, CH 2 or NR 6 , R 6 is selected from hydrogen and CrC 6 -alkyl, and the methylene group in the formula (II) is optionally CVCV alkyl, fluoro group Or a chloro group substituted one or two times; conh2; S02NH2; 191 20 200932732 CONH2 or so2nh2, wherein the amine functionality is selected from Ci_C6-alkyl, C6-Ci〇-aryl or C6-Ci〇-aryl -Ci_C6-alkyl group residues substituted one or two times, and in the case of a di-crc6-alkyl substituted amine functionality, the alkyl residues may combine to form a 5 or 6 5 member ring Sulfhydryl; hydroxy; *Schottky; cyano; 10 fluorinated fluorenyl; halogen selected from fluoro, chloro, bromo or iodo; cf3; OCF3; or one up to 10 Saturated atomic composition, a saturated or aromatic 15 heterocyclic ring system which is optionally substituted one or more times by: CVQ-alkyl, QQ-alkoxy, COOH, S03H, amine, sulfhydryl, thiol, a base, a cyano group, a fluoro group, a chloro group, a molybdenyl group, an iodo group, a CF3 or OCF3; and any two or more of R1 to R5 thereof may be combined to form a saturated 20 unsaturated, unsaturated Or an aromatic homocyclic or heterocyclic ring system; m represents 0, 1, 2, 3, 4, 5 or 6; Y represents: a) hydrogen; tOCVC^-alkyl, monounsaturated or polyunsaturated C2-C18- 200932732 alkylene, C3-C8-cycloalkyl, C6-C1 (r aryl, c6-c1 (r aryl-CVCV alkyl, CVCV alkoxy, c6_Ci()_aryloxy, c6_c10-aryl -Q-C8-alkoxy, CrC: 6-alkoxycarbonyl, c6-C10-aryloxycarbonyl, CVCV aryl-CrQ-morphoxycarbonyl, Q-CV alkyl, C6-C1 ( r arylcarbonyl, c6-c10-aryl-CVCV alkylcarbonyl, Crc6-alkyl sulfhydryl, c6-c1 (r arylcarboxy, Q-CV thiolthio, CVCnr aryl thiol, Cl_c6 _alkylmercaptocarbonyl, C3-Cs-cycloalkylfluorenylcarbonyl, c6-C10-aryldecylcarbonyl, CVCV alkyldecylcarboxy, C6- C1()-aryldecylcarboxyl, Ci-CV alkylsulfonic acid, C6-C10-aryl sulfhydryl, q-CV polyoxythiol, C6_C10-aryloxythio or one by up to 1〇 A saturated, unsaturated or aromatic heterocyclic ring system consisting of one atom, each of which is optionally substituted one or more times by: bl) Ci_C6_ alkyl, C3-C8-cycloalkyl, C6-Ci 〇-aryl, c6-c1 (raryl-CVCV alkyl, CVCV alkoxy, c6-c1 (r aryloxy, C6-CiQ-aryl-C!-C8-alkoxy, Ci_C6_ Oxyl I carbon, c6-c1 (r aryloxycarbonyl, CVCur aryl-Ci-Cs-alkoxycarbonyl, crc6-alkylcarbonyl, C6-C1 (rarylcarbonyl, C6-C1()- aryl-Ci_C8-alkyl group, Ci-C6-alkyl group, C6-Ci〇-aryl group, CVCV alkyl thio group, C6-C10-aryl thio group, Ci-CV alkane Base carbonyl, c3-c8-cycloalkylfluorenylcarbonyl, c6-c1()-arylsulfenyl, Ci-C6-nonylthiol, C6-C1()-aryl thiol , CrC6-alkylsulfonyl, C6-C1()-arylsulfonic acid, (VCV alkyloxythio, C6-CiQ-aryloxycarbonyl, each of which is selective 193 200932732 Replace each time Multiple times: Ci-CV alkyl; CVCV alkoxy; CONH2; S02NH2; wherein the amine functionality is replaced by VC6-alkyl one or two times CONH2 or S02NH2; so3h; co2h; amine group; Substituents in the following groups are substituted for one or more amine groups: CrCV alkyl, C6-C10-aryl, C6-C10-aryl-CrC6-alkyl, CrCV alkylcarbonyl, C6-C1()- Arylcarbonyl, Cj-Ce-alkylsulfonyl and C6-C1()-arylsulfonyl; sulfhydryl; hydroxy; nitro; cyano; fluoro; chloro; bromo; a plurality of substituents of the iodo group; CF3; or OCF3; © 10 wherein bl) may be combined to form a fused saturated, unsaturated or aromatic homocyclic or heterocyclic ring system; or by:, b2) a thiol group; Sulfhydryl; nitro; cyano; fluoro; chloro; bromo; iodo; CF3; C02H; S03H; OCF3; 15 conh2; so2nh2; conh2 or so2nh2, wherein the amine functionality is Residues selected from the group consisting of crc6-alkyl, c6-c1()-aryl or c6-c1()-arylο-CrCV alkyl are substituted one or two times, and wherein in one of the two groups, two-Q-C6- In the case of an alkyl substituted amine functionality, the alkyl residue can be knotted And forming a 5 or 6 membered ring; an amine group; one or more amine groups substituted with 20 residues selected from the group consisting of CVCV alkyl, c6-c10-aryl, c6-c1 (raryl-crc8) -alkyl, crc6-alkylcarbonyl, c6-c1()-arylcarbonyl, crc6-alkylsulfonyl and c6-c1 (rarylsulfonyl); or one of the following formula (II) Substituted amine group: 194 200932732 5 Ή7] °(ΙΙ) where 0 represents 0 or 1, and W represents oxygen, CH2 or NR6, and R6 is selected from hydrogen and crc6-alkyl and its sub-formula in formula (II) The group may be optionally substituted one or two times: CrC6-alkyl, fluoro or chloro; or: ❹ { b3) - a saturated, unsaturated or aromatic complex consisting of up to 1 atom a ring system, which is optionally substituted one or more times by: CVCV.alkyl; CrC6-alkoxy; COOH; CONH2; 10 S〇2NH2; wherein the amine functionality is crc6-alkyl Substituting once or twice C0NHjS02NH2; S03H; amine group; amine group substituted one or more times with a residue selected from the group consisting of CrC6-alkyl, C6-C1 (raryl, c6-C1()- aryl-CrC6-alkyl, crc6-alkyl-based, C6-C10- Carbonyl group, QQ-alkylsulfonyl group and c6-C10-aryl 15 fluorenyl sulfonyl group; sulfhydryl group; hydroxyl group; nitro group; cyano group; fluoro group; gas group; bromo group; CF3; or 〇CF3; c) S〇3H; amine group; amine group substituted one or more times with a residue selected from the group consisting of CrC6-alkyl, C6-C10-aryl, C6-Cl0- aryl-CrC8-alkyl, CVQ-alkylcarbonyl, c6-C1 (rarylcarbonyl, 20 CrCV alkylsulfonyl and c6-C1 (rarylsulfonyl; c〇NH2; S〇2NH2; Conh2 or so2nh2, wherein the amino functionality is substituted once or twice with a residue selected from the group consisting of CrC6-alkyl, C6-C1()-aryl or C6-C10-aryl-Ci-Cr alkyl; In the case of a bis-^/^alkyl substituted 195 200932732 amine functionality, the alkyl residue may combine to form a 5 or 6 membered ring; sulfhydryl; hydroxy; nitro; cyano; a sulfonyl group; an element selected from the group consisting of a fluoro, chloro, bromo or iodo group; CF3; or 〇cf3; 5 cyclization to form a furadiazolone ring system, provided that the product is produced It is not a compound excluded as specified in Article 24 of the patent application. 90. The method of claim 89, wherein the cyclization of the furadiazolone ring system is achieved by carbon ruthenium chloride, ruthenium or a carbonic acid ester.

196 200932732 四、指定代表圖： (一) 本案指定表圖為：第（）圖。（無) (二) 本表圖之元件符號簡單說明：196 200932732 IV. Designated representative map: (1) The specified table in this case is: ( ). (none) (ii) A brief description of the component symbols in this table:

五、本案若有化學式時，請揭示最能顯示發明特徵的化學式：5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention:

(I) 2(I) 2