TWI294414B

TWI294414B - Amino alcohol derivatives as amadorase inhibitors

Info

Publication number: TWI294414B
Application number: TW93141154A
Authority: TW
Inventors: Shan Yen Chou; Shieh Shung T Chen; Mann Yan Kuo; Shyh Fong Chen; Henry J Tsai
Original assignee: Dev Center Biotechnology
Priority date: 2004-12-29
Filing date: 2004-12-29
Publication date: 2008-03-11
Also published as: TW200621681A

Description

1294414 ( 九、發明說明：【發明所屬之技術領域】本發明係關於做為Amadorase抑制劑的新胺基醇衍生物及其藥學上可接受之鹽類。其中新化合物，特別是如式一之新胺基雙醇及胺基三醇衍生物、其製備方法與含有此類化合物之藥物以及其在藥學上之應用。1294414 (IX. INSTRUCTIONS: [Technical Field] The present invention relates to a novel amino alcohol derivative as an Amadorase inhibitor and a pharmaceutically acceptable salt thereof, wherein the novel compound, in particular, Novel amino diols and amine triol derivatives, processes for their preparation and medicaments containing such compounds and their use in pharmacy.

OH OHOH OH

式一 R，Ra =氫、1-20個碳原子之烧基、芳香烧基、芳香烧基(低破數烧基）、異原子芳香烷基、異原子芳香烷基(低碳數烷基）Formula I, R = hydrogen, alkyl of 1 to 20 carbon atoms, aromatic alkyl group, aromatic alkyl group (low number of alkyl), hetero atomic aromatic alkyl group, hetero atomic aromatic alkyl group (lower alkyl group) )

Rb =氫、低碳數烷基、曱烯芳香烷基、曱烯異原子芳香烷基 n = 〇，=氫、低碳數烷基、芳香烷基、芳香烷基(低破數烷基）、異原子芳香烷基、異原子芳香烧基(低碳數烷基)及(烷氧基）甲基 η = 1，Re=低碳數烷基、芳香烷基(低礙數烷基)及異原子芳香烷基(低碳數烷基）【先前技術】早期認為活體與食物中蛋白質的胺基可在無需酵素存在下與類反應形成Schiff base，再轉變成酮基胺並經由Amadori 重排而穩定，此反應為Maillard反應的早期步驟。經過Maillard 反應的後期步驟後，Amadori重排反應產物會被分解成 3-deoxyglucosone(3DG)。3DG為會攻擊蛋白質中離氨酸基、蛋白氨酸基及色氨酸基片段而產生有害分子的高活性雙羰基分子，且其亦為生成高度醣化體（AGEs)之前驅物，此二者皆與造成糖尿病併發症有關（Baynes，J.W·，S.R· Thorpe，and Μ_Η· Murtiashaw, Nonenzymatic glucosylation of lysine residues in albumin. Methods Enzymol，1984. 106: p. 88-98，Araki，A·， 0296-A20652TWF(N2)；323；Uofung 5 4! 1294414Rb = hydrogen, lower alkyl, decene aromatic, terpene heteroatom aromatic alkyl n = 〇, = hydrogen, lower alkyl, arylalkyl, arylalkyl (low alkyl) a hetero atomic aromatic alkyl group, a hetero atom aromatic alkyl group (lower alkyl group), and an (alkoxy)methyl group η = 1, Re = a lower alkyl group, an aromatic alkyl group (lower alkyl group), and Heteroatom arylalkyl (lower alkyl) [Prior Art] It is thought that the amine group of the protein in living organisms and food can react with a class to form a Schiff base without the presence of an enzyme, and then convert to a ketoamine and rearrange through Amadori. Stable, this reaction is an early step in the Maillard reaction. After a later step in the Maillard reaction, the Amadori rearrangement reaction product is broken down into 3-deoxyglucosone (3DG). 3DG is a highly active dicarbonyl molecule that attacks harmful molecules such as lysine, proline and tryptophanyl fragments in proteins, and is also a precursor to the formation of highly glycated bodies (AGEs), both of which Both are associated with complications of diabetes (Baynes, JW, SR· Thorpe, and Μ_Η· Murtiashaw, Nonenzymatic glucosylation of lysine residues in albumin. Methods Enzymol, 1984. 106: p. 88-98, Araki, A·, 0296- A20652TWF(N2); 323; Uofung 5 4! 1294414

Oxidative stress and diabetes mellitus: a possible role of alpha-dicarbonyl compounds in free radical formation. Nippon Ronen Igakkai Zasshi，1997. 34(9): p. 716-20·)。對糖尿病患者而言，3DG的累積會造成嚴重的糖尿病併發症，如腎臟病變、粥狀動脈硬化、眼球病變以及神經病變。近年來對於糖尿病併發症的研究發現Amadorase為催化 3DG產生之酵素，而3DG主要是經由酵素催化路徑生成，次要路徑則是經由非酵素催化重排、脫水以及含果醣離氨酸蛋白質的裂解而生成。Dynamis公司證實了 3DG可於活體中經由酵素催化反應生成（式二）。Amadorase將FL雄酸化以形成 fructoselysine3-phosphate(FL3P)，緊接著 FL3P 自發分解成離氨酸，磷及3DG。經由酵素催化生成之3DG是非酵素催化路徑生成的二十倍。DYN12是第一個有藥效的Amadorase抑制劑，其抑制 Amadorase 作用而阻止 FL3P 的生成。由於過程中的催Oxidative stress and diabetes mellitus: a possible role of alpha-dicarbonyl compounds in free radical formation. Nippon Ronen Igakkai Zasshi, 1997. 34(9): p. 716-20·). For diabetics, the accumulation of 3DG can cause serious diabetic complications such as kidney disease, atherosclerosis, eyeball lesions, and neuropathy. In recent years, studies on diabetic complications have found that Amadorase is an enzyme that catalyzes the production of 3DG, while 3DG is mainly produced via an enzyme-catalyzed pathway, and the secondary pathway is through non-enzymatic catalytic rearrangement, dehydration, and cleavage of fructose-containing lysine-containing proteins. generate. Dynamis has confirmed that 3DG can be produced in vivo by enzyme-catalyzed reactions (Formula 2). Amadorase acidifies FL to form fructoselysine3-phosphate (FL3P), followed by spontaneous decomposition of FL3P into amino acid, phosphorus and 3DG. The 3DG produced by enzyme catalysis is twenty times larger than the non-enzyme catalytic pathway. DYN12 is the first potent Amadorase inhibitor that inhibits the production of FL3P by inhibiting Amadorase. Due to the reminder in the process

fructosamine_3-kinase (F3k，Amadorase)為生成 3DG 化劑，使其成為一治療上的目標。3DG在生物學的形成路徑及現有藥理學上的去毒劑，三氮雜苯的去毒作用詳列於下（式二）。與酵素催化路徑比起來，由於三氮雜苯的去毒作用需要當量t 的三氮雜苯而顯得效率較差。 0296-A20652TWF(N2)；323；Uofung 6 1294414 葡萄糠+離氨酸酵素催化路徑果酶‘氨酸· (抑^ 產生3DG之非酵素催化路徑Fructosamine_3-kinase (F3k, Amadorase) is a therapeutic target for the production of 3DG agents. The path of biological formation of 3DG and the existing pharmacological detoxification agent, the detoxification of triazabenzene is detailed below (Formula 2). Compared with the enzyme catalytic pathway, the detoxification of triazabenzene requires an equivalent t of triazabenzene and is inefficient. 0296-A20652TWF(N2); 323; Uofung 6 1294414 Grape 糠 + lysine enzyme catalytic pathway fruit enzyme ‘acid · ( suppresses 3DG non-enzyme catalytic pathway

Pi 三氮雜苯 t 胺基胍之藥理去毒作用 3DG c +離氨酸+鱗 3 DF 酸還原酵素之巾和去毒作用式二Pi triazabenzene t-aminopurine pharmacological detoxification 3DG c + lysine + scale 3 DF acid reducing enzyme towel and detoxification

ΐ> AGEs I 糖尿病性腎臟病變及其他併發症美國專利USP6,004,958(1999)揭示有利用小分子離氨酸-糖衍生物來抑制F3k作用而降低體内3dg量的可行性。人體對此抑制劑的負荷程度雖佳，然而其低生體可用率及高Ki值為其缺點。此類典型的化合物舉例如下（式三）。 ho2cΐ> AGEs I Diabetic Nephropathy and Other Complications US Patent 6,004,958 (1999) discloses the feasibility of using small molecule lysine-sugar derivatives to inhibit F3k action and reduce the amount of 3dg in vivo. The human body has a good load on this inhibitor, but its low bioavailability and high Ki value are its disadvantages. Typical examples of such compounds are as follows (Formula 3). Ho2c

nh2Nh2

3-0-甲基山梨醇離氨酸 *s-型：山梨醇 R-型：甘露醇式三【發明内容】本lx明揭示種新糸列之有藥效的Amadorase抑制劑。以新陳代谢的觀點來看，本發明揭示之新化合物較習知之胺基醣類抑制劑穩疋且較具有發展潛力。本新化合物具有良好 0296-A20652TWF(N2)；323；Uofung 7 1294414 - 抑制Amadorase的活性且能減輕糖尿病併發症，如腎臟病變、粥狀動脈硬化、眼球病變及神經病變的嚴重程度。這類化合物結構上包含長鏈片段及吸水特性使其在預防皮膚病，如異位性皮膚炎、蓴麻疹與其他濕疹性皮膚炎和皮膚老化上有特殊功效。Dynamis公司發現3DG不只存在於腎臟亦表現於皮膚上，並接著在實驗上證明和未給藥的糖尿病老鼠相比，以此發明之抑制劑來治療患有糖尿病的老鼠八個月後能維持這些老鼠的肌膚彈性。根據本發明，在此提出下述（式一）之化合物及其藥學上可接受之鹽類與水合物：3-0-Methylsorbitol lysine *s-type: Sorbitol R-type: Mannitol Formula III [Summary of the Invention] This is a novel pharmacological Amadorase inhibitor disclosed by the present invention. From the standpoint of metabolism, the novel compounds disclosed in the present invention are more stable and more promising than the conventional amine saccharide inhibitors. The new compound has good 0296-A20652TWF(N2); 323; Uofung 7 1294414 - inhibits the activity of Amadorase and can alleviate the complications of diabetic diseases such as renal lesions, atherosclerosis, eyeball lesions and neuropathy. These compounds structurally contain long-chain fragments and water-absorbing properties that make them particularly effective in preventing skin diseases such as atopic dermatitis, urticaria and other eczema dermatitis and skin aging. Dynamis found that 3DG is present not only in the kidney but also on the skin, and then experimentally demonstrated that the inhibitors of this invention can be used to treat diabetic rats for eight months compared to unadministered diabetic mice. The skin elasticity of the mouse. According to the present invention, the following compound of the formula (1) and pharmaceutically acceptable salts and hydrates thereof are proposed:

OH 0H R \OH 0H R \

Ra^ 式一 R，Ra =氫、1-20個碳原子之烷基、芳香烷基、芳香烷基(低破數烷基）、異原子芳香烷基、異原子芳香烷基(低碳數烷基）Ra^ Formula R, Ra = hydrogen, alkyl of 1-20 carbon atoms, arylalkyl, arylalkyl (low-number alkyl), heteroatom arylalkyl, heteroatom arylalkyl (low carbon number) alkyl)

Rb =氫、低碳數烷基、甲烯芳香烷基、甲烯異原子芳香烷基 η = 0，Re =氫、低碳數烷基、芳香烷基、芳香烷基(低碳數烷基）、異原子芳香烷基、異原子芳香烷基(低碳數烷基)及(烷氧基）甲基 η = 1，Re=低礙數烷基、芳香烷基(低破數烷基)及異原子芳香烷基(低碳數烷基）下述化合物為本發明較佳實施例中所揭示之化合物： 3-甲氧基-1-壬胺基·2,4-壬雙醇 3_苯曱氧基-1-十二烷胺基-2-己醇 3-苯甲氧基-(3-苯基丙胺基）-2-己醇 3-苯甲氧基-1-十二烷胺基-4-甲氧基-2-丁醇 3-苯曱氧基_4_甲氧基-1-辛胺基-2-丁醇 3-苯甲氧基-1_十二烷胺基-2-己醇 3-苯甲氧基-1-十六烷胺基-4-甲氧基-2-丁醇 3-苯甲氧基-1-十五烷胺基-2-己醇 0296-A20652TWF(N2)；323；Uofung 8 1294414 3_苯甲氧基-1-十四烧胺基-己醇 3-苯甲氧基十三烧胺基己醇 1-十八烷胺基_3十比啶-2-甲氧基）_2_己醇 1-十八烷胺基-3-(°比啶-3-甲氧基）-2-己醇 1-苯甲氧基-3-十八烧胺基-2-丙醇 1-苯甲氧基-1-十八烧胺基-2-己醇 1-辛胺基-3-(ϋ比11 定-2-甲氧基）-2•己醇 1-己胺基-3-(°比咬-2-甲氧基）-2-己醇 1-丁胺基-3-(σ比定-2 -甲氧基）-2-己醇式-之化合物至少具有-不對稱中心，如式一之化合物中以星號標示之碳’且有一個以上之立體異構物及其混合物與消旋化合物。本發明更包括式一之化合物所對應之生物學及藥學上可接受之鹽類。這些鹽類可由各種有機或無機酸來合成，包括甲碏酸、鹽酸、曱苯磺酸、硫酸、順丁烯二酸、醋酸、檸檬酸及= 酸，但不侷限於上述酸類。例如，式一之化合物可在適當溶劑，如甲醇、乙醇或乙酸乙酯中與鹽酸溶液反應來形成鹽酸鹽。若有需要’這些鹽類亦會用來測定其抑制Amad〇rase之活性。當n= 0，式一之化合物可以下述步驟製備： a) 以上式化合物與下式化合物進行反應，其中R及^之定義如上述 0RbRb = hydrogen, lower alkyl, methoxyalkyl, methene heteroalkyl η = 0, Re = hydrogen, lower alkyl, arylalkyl, arylalkyl (lower alkyl) ), heteroatomic arylalkyl, heteroatom arylalkyl (lower alkyl) and (alkoxy)methyl η = 1, Re = lower alkyl, arylalkyl (low alkyl) And a hetero atomic aromatic alkyl group (lower alkyl group) The following compounds are the compounds disclosed in the preferred embodiments of the invention: 3-methoxy-1-indenyl group · 2,4-decyl diol 3_ Phenyloxy-1-dodecylamino-2-hexanol 3-benzyloxy-(3-phenylpropylamino)-2-hexanol 3-benzyloxy-1-dodecanamine 4-methoxy-2-butanol 3-benzofluorenyl_4-methoxy-1-octylamino-2-butanol 3-benzyloxy-1-dodecylamino- 2-hexanol 3-benzyloxy-1-hexadecylamino-4-methoxy-2-butanol 3-benzyloxy-1-pentadecylamino-2-hexanol 0296- A20652TWF(N2); 323; Uofung 8 1294414 3_Benzyloxy-1-tetradecylamine-hexanol 3-benzyloxytridecylamine hexanol 1-octadecylamine _3 Bisidine-2-methoxy)-2-hexanol 1-octadecylamino-3-(° ratio pyridine-3-methoxy 2-hexanol 1-benzyloxy-3-octadecylamine-2-propanol 1-benzyloxy-1-octadecylamine-2-hexanol 1-octylamino -3-(ϋ1-11-2-methoxy)-2•hexanol 1-hexylamino-3-(° ratio bit-2-methoxy)-2-hexanol 1-butylamino- The compound of 3-(σ-Butidine-2-methoxy)-2-hexanol-type has at least an asymmetric center, such as a carbon-labeled carbon in the compound of Formula I, and has more than one stereoisomer And mixtures thereof and racemic compounds. The invention further encompasses biologically and pharmaceutically acceptable salts corresponding to the compounds of formula 1. These salts can be synthesized from various organic or inorganic acids, including formic acid, hydrochloric acid, toluenesulfonic acid, sulfuric acid, maleic acid, acetic acid, citric acid and acid, but are not limited to the above acids. For example, a compound of formula A can be reacted with a solution of hydrochloric acid in a suitable solvent such as methanol, ethanol or ethyl acetate to form the hydrochloride salt. If necessary, these salts are also used to determine their activity against Amad〇rase. When n = 0, the compound of formula 1 can be prepared by the following steps: a) The compound of the above formula is reacted with a compound of the formula wherein R and ^ are as defined above.

Rc 〇296-A2〇652TWF(N2)；323；Uofung 1294414 其中定義Rbi Re如上述，具有單一立體異構物並於適當溶劑或無需溶劑的條件下反應；以及 b)選擇性地與藥學用之酸反應以製得藥學上可接受之鹽類。當n= 1，式一之化合物可以下述步驟製備：Rc 〇 296-A2 〇 652TWF(N2); 323; Uofung 1294414 wherein Rbi Re is as defined above, has a single stereoisomer and is reacted in a suitable solvent or without a solvent; and b) is selectively used in pharmacy The acid is reacted to produce a pharmaceutically acceptable salt. When n = 1, the compound of formula 1 can be prepared by the following steps:

OH 0HOH 0H

Ra>^V^RC R 0Rb 式一 a) R、Ra>^V^RC R 0Rb Equation 1 a) R,

〇a.NH〇a.NH

Ra 以上式化合物與下式化合物進行反應，其中R及Ra2定義如上述Ra compound of the above formula is reacted with a compound of the formula wherein R and Ra2 are as defined above

Kv/u\^〇H Rb〇^一bH 其中妒及Re係如上述所定義之化合物，其中具有猶氫化鈉或硼氰氳化鈉，並於適當溶劑或混合溶劑的條件下反應；以及 b)選擇性地與藥學用之酸反應以製得藥學上可接受之鹽類。若使用適當的四氫呋喃類中間物則可合成不同之式一化合物0 0296-A20652TWF(N2)；323；Uofung 10 1294414 ^為讓本發明之上述和其他目的、特徵、和優點能更明顯易 «，以下敘述舉出一些中間產物以及本發明化合物的製備方法作詳細說明：【實施方式】敘述1 製備胺基三醇衍生物的標準步驟：Kv/u\^〇H Rb〇^-bH wherein hydrazine and Re are a compound as defined above, which has sodium hydride or sodium borohydride, and is reacted in a suitable solvent or a mixed solvent; Optionally, reacting with a pharmaceutically acceptable acid to produce a pharmaceutically acceptable salt. If a suitable tetrahydrofuran intermediate is used, a different compound of formula 0 0296-A20652TWF(N2); 323; Uofung 10 1294414 can be synthesized to make the above and other objects, features and advantages of the present invention more apparent. The following describes some intermediate products and preparation methods of the compounds of the present invention are described in detail: [Embodiment] Description 1 Standard steps for preparing an aminotriol derivative:

勾大量製備3-0-甲基二丙@同葡萄糖BLarge amount of preparation of 3-0-methyldipropyl@with glucose B

將第三丁氧基鉀（13.5 g，〇·12 m〇1)加入二丙酮葡萄糖A 〇5·6 g，〇·〇6 mol)的無水四氫呋喃（25〇 mL)溶液中並於室溫下持、、攪拌，再將甲基破（22·〇 g，〇155 m〇1)的無水四氫呋喃（5〇 mL)溶液加入，迴流6小時後過濾、濃縮並以二氯甲烷稀釋，所知之有機層以水清洗兩次，經硫酸鎂乾燥後減壓濃縮得黃色油狀化合物Β (16·9 g)。 b)部分水解3-0-甲基二丙鲷葡萄糖B而合成化合物c 0296-A20652TWF(N2);323;Uofung 11 1294414Potassium tert-butoxide (13.5 g, 〇·12 m〇1) was added to diacetone glucose A 〇5·6 g, 〇·〇6 mol) in anhydrous tetrahydrofuran (25 〇mL) and at room temperature After stirring and stirring, a solution of methyl ruthenium (22·〇g, 〇155 m〇1) in anhydrous tetrahydrofuran (5 〇mL) was added, and the mixture was refluxed for 6 hours, filtered, concentrated and diluted with dichloromethane. The organic layer was washed twice with water, dried over magnesium sulfate b) partial hydrolysis of 3-0-methyldipropionin glucose B to synthesize compound c 0296-A20652TWF(N2); 323; Uofung 11 1294414

將濃鹽酸（4.0 mL)加入冰浴下之粗產物B (16.9 g，上述步驟所得）的甲醇（86 mL)及水（130 mL)之懸浮溶液中並於室溫下持續攪拌，反應隔夜後於〇 °C下加入氫氧化鈉（2.0 g，0.05 mol)，於40 °C以下將反應混合物濃縮再加入少量水稀釋，所得之溶液以異丙基醚清洗來去除未反應之化合物B後濃縮，殘餘物再以丙酮稀釋並以燒結玻璃漏斗過濾、減壓濃縮而得中間產物C(13.3g，兩步驟合計粗產率為QS.OrO’HNMRCCDCh) 5_73 (m，1H)，4.55 (m，1H)，3.96 (m，1H)，3.76 (m，1H)，3.70 (m， 1H)，3_66 (m，1H)，3.48 (m，1H)，3.22 (s，3H)，1.36 (s，3H)，1.22 (s，3H) 〇Concentrated hydrochloric acid (4.0 mL) was added to a suspension of the crude product B (16.9 g, obtained in the above step) in methanol (86 mL) and water (130 mL) and stirred at room temperature overnight. Sodium hydroxide (2.0 g, 0.05 mol) was added at 〇 ° C, and the reaction mixture was concentrated at 40 ° C or less and diluted with a small amount of water. The resulting solution was washed with isopropyl ether to remove unreacted compound B and concentrated. The residue was diluted with acetone and filtered with a fritted glass funnel, and concentrated under reduced pressure to give Intermediate C (13.3 g, mp. s. 1H), 3.96 (m, 1H), 3.76 (m, 1H), 3.70 (m, 1H), 3_66 (m, 1H), 3.48 (m, 1H), 3.22 (s, 3H), 1.36 (s, 3H) ), 1.22 (s, 3H) 〇

c)製備3-0·甲基_1，2-異丙叉-D-呋喃糖Dc) Preparation of 3-0·methyl-1,2-isopropylidene-D-furanose D

將過氧化碘基鈉（11.5 g，53.76 mmol)加入中間產物C(12_8 g，〜54.7mmol)的水（100mL)溶液中並攪拌1小時，所得之溶液以氯仿（100 ML X 3)萃取，將有機層合併以水清洗，經硫酸鎂乾燥後減壓濃縮得黃色油狀物D (4·9 g)。"HNMRCCDCh) 9.64 (s5 1H)，6.09(m，1H)，4 .63(m，1H)，4 .54(m，1H)，4.12(m，1H)， 0296-A20652TWF(N2)；323；Uofung 12 1294414 3·36 (s，3H)，1·48 (s，3H)，1_33 (s，3H)。 d) 3-0-曱基-1，2-異丙叉-D-呋喃糖D與磷酸鹽進行Wittig反應合成中間產物 E (6-甲氧基-2,2_二曱基·5·苯甲基四氫呋喃[2,3-J][l，3]二噁烷）Sodium iodate sodium (11.5 g, 53.76 mmol) was added to a solution of intermediate C (12_8 g, ~54.7 mmol) in water (100 mL) and stirred for 1 hour, and the obtained solution was extracted with chloroform (100 ML X 3 ). The organic layer was combined with EtOAc (EtOAc m. "HNMRCCDCh) 9.64 (s5 1H), 6.09 (m, 1H), 4.63 (m, 1H), 4. 54 (m, 1H), 4.12 (m, 1H), 0296-A20652TWF (N2); Uofung 12 1294414 3·36 (s, 3H), 1·48 (s, 3H), 1_33 (s, 3H). d) 3-0-mercapto-1,2-isopropylidene-D-furanose D and phosphate were subjected to Wittig reaction to synthesize intermediate E (6-methoxy-2,2-didecyl·5·benzene Methyltetrahydrofuran [2,3-J][l,3]dioxane)

將含60 %氫化納的礦油（0.6 g，15.90 mmol)加入攝酸鹽 F(4.0 g，9.23 mmol)的二甲基亞砜（20 mL)懸浮溶液中，於室溫中攪拌1小時後再將中間產物D (1.86 g, 9.20 mmol)的二甲氧基乙烷（2 mL)溶液加入。於60 °C下反應1.5小時後將反應混合物倒入冰水中，以體積比1/2之異丙基醚/乙酸乙酯混和溶液萃取上述溶液兩次，將有機層合併以水清洗，經硫酸鎂乾燥後濃縮。以矽膠管柱色層分析法（乙酸乙酯/正己烷：1/5)純化得黃色油狀中間產物E (0.94 g，56.0 %)。以下之中間產物皆依上述之方法製備。 5-[2-(4-漠、苯基）-乙稀基]-6-甲氧基-2,2-二甲基四氣11 夫喃 [2,3d][l，3]二噁烷A 60% hydrogenated sodium mineral oil (0.6 g, 15.90 mmol) was added to a suspension of the acid salt F (4.0 g, 9.23 mmol) in dimethyl sulfoxide (20 mL) and stirred at room temperature for 1 hour. A solution of intermediate D (1.86 g, 9.20 mmol) in dimethoxyethane (2 mL) was then added. After reacting at 60 ° C for 1.5 hours, the reaction mixture was poured into ice water, and the solution was extracted twice with a volume ratio of 1/2 isopropyl ether / ethyl acetate mixed solution, and the organic layer was combined and washed with water, sulfuric acid. The magnesium is concentrated after drying. Purification by hydrazine gel chromatography (ethyl acetate / hexanes: 1/5) afforded the crude oily product E (0.94 g, 56.0 %). The following intermediates were prepared in the manner described above. 5-[2-(4-Mo, Phenyl)-ethenyl]-6-methoxy-2,2-dimethyltetrasole 11 Furan [2,3d][l,3]dioxane

0296-A20652TWF(N2)；323；Uofung 13 1294414 JH NMR (CDC13) 7.47 (m5 2H)? 7.24 (m? 2H), 6.73 (d5 J = 11.5 Hz, 1H)，5.94 (m，2H)，4.92 (m，1H)，4 64 (m，lH)，3·64 (m，1H)，3.44 (s，3H)，1.43 (s，3H)，1.33 (s，3H) ’ 6-曱氧基-2,2-二甲基I戊+稀基四氫咬喃[2,3_rf][1，3]二噁烷0296-A20652TWF(N2); 323; Uofung 13 1294414 JH NMR (CDC13) 7.47 (m5 2H)? 7.24 (m? 2H), 6.73 (d5 J = 11.5 Hz, 1H), 5.94 (m, 2H), 4.92 ( m,1H),4 64 (m,lH),3·64 (m,1H),3.44 (s,3H),1.43 (s,3H),1.33 (s,3H) '6-decyloxy-2 ,2-Dimethyl I pentyl + dilute tetrahydrocarbamate [2,3_rf][1,3]dioxane

4 NMR (CDC13) 5.86 (m，1H)，5 62 (m，1H)，5 52 (m lH)，4 % (m，1H)，4·53 (m，1H)，3·53 (m，1H)，3.34 (s，3H)，2.03 (m，2H)， 1.47 (s，3H)，1.36 (m，2H)，le27 (s，3H)，〇 86 (t，j = 7 〇 Hz，3H)4 NMR (CDC13) 5.86 (m, 1H), 5 62 (m, 1H), 5 52 (m lH), 4 % (m, 1H), 4·53 (m, 1H), 3·53 (m, 1H), 3.34 (s, 3H), 2.03 (m, 2H), 1.47 (s, 3H), 1.36 (m, 2H), le27 (s, 3H), 〇 86 (t, j = 7 〇Hz, 3H )

e)氯化中間產物E而合成中間產物Fe) chlorination of intermediate E to synthesize intermediate F

將中間產物E溶於甲醇中球氫化而合成中間產物F。以10 % Pd/C為催化劑用氫氣The intermediate product E was synthesized by dissolving the intermediate E in methanol to hydrogenate the intermediate product F. Hydrogen with 10% Pd/C as catalyst

以下之中間產物皆依上述之方法製 6_甲氧基_2,2-二甲基_5_戊烷基四氫〇296-A2〇652TWF(N2)；323；Uofung 14 1294414The following intermediates were prepared according to the above procedure: 6-methoxy-2,2-dimethyl-5-pentyltetrahydroanthracene 296-A2〇652TWF (N2); 323; Uofung 14 1294414

f)水解中間產物F而合成中間產物Gf) hydrolysis of intermediate product F to synthesize intermediate G

將濃鹽酸（5·0 mL)加入中間產物F (2·95 g)的甲醇（3〇及水（30mL)之懸浮溶液中持續攪拌丨小時，再將醋酸（i〇mL) 加入並於40 QC下攪拌5小時，於冰浴下以10 %氳氧化鈉中和後濃縮，所得之殘餘物以氯仿稀釋並以水清洗兩次，有機層經硫酸鎮乾燥後濃縮。以石夕膠管柱色層分析法（乙駿乙g旨/正己烷：1/5)純化得黃色油狀中間產物G (3.2 g，〜100 %)。 g)中間產物G經還原胺化反應而合成胺基三醇衍生物11 1-(2-二甲胺基乙胺基）-3-甲氧基-6-苯基-2,4-己雙醇（H) 0296-A20652TWF(N2)；323；Uofung 15 1294414Concentrated hydrochloric acid (5.0 mL) was added to a suspension of intermediate product F (2·95 g) in methanol (3 Torr and water (30 mL), stirring was continued for a few hours, then acetic acid (i〇mL) was added and added to 40 The mixture was stirred for 5 hours under QC, neutralized with 10% sodium sulphate in an ice bath, and concentrated. The residue was diluted with chloroform and washed twice with water. The organic layer was dried over sulfuric acid and then concentrated. The layer analysis method (BJJJ / n-hexane: 1/5) was purified to obtain a yellow oily intermediate G (3.2 g, 〜100%). g) Intermediate G was reductively aminated to synthesize aminotriol Derivative 11 1-(2-dimethylaminoethylamino)-3-methoxy-6-phenyl-2,4-hexanedimethanol (H) 0296-A20652TWF (N2); 323; Uofung 15 1294414

NaCNBH3 -► EtOH H2〇NaCNBH3 -► EtOH H2〇

Me、N，^NH2Me, N, ^NH2

Me 將硼氫氰化鈉（0.21 g)，二曱基乙二胺的乙醇（5 mL)溶液加入攪拌下的中間產物G (0.32 g)的體積比1/2之乙醇/水混和溶液中並於氮氣下迴流隔夜。反應混合物濃縮後以氯仿稀釋再以水清洗兩次，分離之有機層經硫酸鎂乾燥後濃縮。以矽膠管柱色層分析法（曱醇/乙酸乙酯：1/20且含1 %之三乙基胺）純化得黃色油狀胺基三醇衍生物Η。 3-甲氧基小壬胺基_2,4_壬雙醇Me A solution of sodium borohydride (0.21 g) and diethylene glycol diamine in ethanol (5 mL) was added to the stirred intermediate product G (0.32 g) in a volume ratio of 1/2 ethanol/water mixture. It was refluxed overnight under nitrogen. The reaction mixture was concentrated, diluted with EtOAc EtOAc. The yellow oily aminotriol derivative oxime was purified by silica gel column chromatography (methanol/ethyl acetate: 1/20 and 1% triethylamine). 3-methoxyberberamido-2,4-indole diol

OH 0ΗOH 0Η

Η3(Τό 將硼氳氰化鈉（0.6 g，9.55 mmol)加入4_甲氧基-5-戊烷基-四氫吱喃-2,3_雙醇（0·90 g，4.40 mmol)和壬燒胺鹽酸鹽（0.80 g， 4.45 mmol)的甲醇（15 mL)及水（3 mL)的混合溶液中並迴流18 小時後濃縮。所得殘餘物以乙酸乙酯及水稀釋攪拌，分離之有機層以水清洗兩次再經硫酸鎂乾燥後濃縮。以矽膠管柱色層分 0296-A20652TWF(N2)；323；Uofung 16 1294414 析法（乙酸乙酯/正己烷：1/1至乙酸乙酯再至甲醇/乙酸乙酯： 1/20)純化得預期產物（0·11 g)。4 NMR (CDC13) 3.92 (m，1H)， 3.75 (m，1H)，3·53 (s，3H)，3.10 (s，1H)，2·86 (m，2H)，2.72 (m， 2H)，1.55, 1.26 (each m，22H)，0.91，0.88 (each t，J = 7.0 Hz，6H)· LC/MS 332.5 (M++1)。 6-(4 -氣苯基)-1 -己胺基-3-甲氧基-2，4-己雙醇Η3(Τό Add sodium borohydride (0.6 g, 9.55 mmol) to 4-methoxy-5-pentanyl-tetrahydrofuran-2,3-diol (0·90 g, 4.40 mmol) and To a mixed solution of sulphuric acid hydrochloride (0.80 g, 4.45 mmol) in methanol (15 mL) and water (3 mL). The organic layer was washed twice with water and dried over magnesium sulfate and then concentrated, and then evaporated, and then evaporated. Purification of the ester to methanol/ethyl acetate: 1/20) to give the desired product (0·11 g). 4 NMR (CDC13) 3.92 (m,1H), 3.75 (m,1H),3·53 (s,3H) ), 3.10 (s, 1H), 2·86 (m, 2H), 2.72 (m, 2H), 1.55, 1.26 (each m, 22H), 0.91, 0.88 (each t, J = 7.0 Hz, 6H)· LC/MS 332.5 (M++1). 6-(4-Phenylphenyl)-1-hexylamino-3-methoxy-2,4-hexanediol

lU NMR (CD3OD) 7.09 (m? 4H)? 3.96 (m? 1H)? 3.75 (m5 1H), 3.43 (s，3H)，3.25 (m，1H)，2.50-3.00 (m，4H)，1.75 (m，2H)，1.50 (m， 4H)，1.25 (m，8H)，0.78 (t，J = 7.0 Hz，3H)· LC/MS 358.0 (M++1)· 6-(4 -氣苯基)-3-甲氧基-1-辛胺基_2,4-己雙醇lU NMR (CD3OD) 7.09 (m? 4H)? 3.96 (m? 1H)? 3.75 (m5 1H), 3.43 (s, 3H), 3.25 (m, 1H), 2.50-3.00 (m, 4H), 1.75 ( m, 2H), 1.50 (m, 4H), 1.25 (m, 8H), 0.78 (t, J = 7.0 Hz, 3H)· LC/MS 358.0 (M++1)· 6-(4-Phenylphenyl) )-3-methoxy-1-octylamino 2,4-hexyl diol

^ NMR (CD3OD) 7.09 (m，4H)，3.96 (m，1H)，3.75 (m，1H)，3.40 (s，3H)，3.25 (m，1H)，2.50-3.00 (m，4H)，1.75 (m，2H)，1.50 (m， 4H)，1.25 (m，12H)，0_76 (t，J = 7_0 Hz，3H)· LC/MS 386.0 (M++l). 6-(4-氣苯基)-1-葵胺基-3-甲氧基-2，4-己雙醇 0296-A20652TWF(N2)；323；Uofung 17 1294414^ NMR (CD3OD) 7.09 (m, 4H), 3.96 (m, 1H), 3.75 (m, 1H), 3.40 (s, 3H), 3.25 (m, 1H), 2.50-3.00 (m, 4H), 1.75 (m, 2H), 1.50 (m, 4H), 1.25 (m, 12H), 0_76 (t, J = 7_0 Hz, 3H)· LC/MS 386.0 (M++l). 6-(4-benzene Base)-1-amylamino-3-methoxy-2,4-hexanediol 0296-A20652TWF (N2); 323; Uofung 17 1294414

lU NMR (CD3OD) 7.09 (d? J = 8.0 Hz, 2H)? 7.05 (d5 J = 8.0 Hz? 2H)，3.96 (m，1H)，3.75 (m，1H)，3.35 (s，3H)，3.25 (m，1H)， 2.50-3.00 (m，6H)，1.75 (m，2H)，1·50 (m，4H)，1.15 (m，14H)， 0.75 (t5 J = 7.0 Hz? 3H). LC/MS 414.0 (M++l). 6-(3 -氣苯基)-1 -(2 -二甲胺基乙胺基）-3-甲氧基·2，4_己雙醇lU NMR (CD3OD) 7.09 (d? J = 8.0 Hz, 2H)? 7.05 (d5 J = 8.0 Hz? 2H), 3.96 (m, 1H), 3.75 (m, 1H), 3.35 (s, 3H), 3.25 (m,1H), 2.50-3.00 (m,6H), 1.75 (m,2H),1·50 (m,4H), 1.15 (m,14H), 0.75 (t5 J = 7.0 Hz? 3H). LC /MS 414.0 (M++l). 6-(3-Phenylphenyl)-1 -(2-dimethylaminoethylamino)-3-methoxy-2,4-hexyl diol

巾 NMR (CDC13) 7·28 (s，1H)，7.10-7.22 (m，3H)，4_25 (m，1H)， 3.90 (m，1H)，3.45 (s，3H)，3.25 (m，1H)，2.50-3.00 (m，8H)，2.37 (s，6H)，1.75, 1.90 (each m，2H). LC/MS 345.0 (M+). 1-丙烯胺基-3_甲氧基-6-苯基-2,4_己雙醇Towel NMR (CDC13) 7·28 (s, 1H), 7.10-7.22 (m, 3H), 4_25 (m, 1H), 3.90 (m, 1H), 3.45 (s, 3H), 3.25 (m, 1H) , 2.50-3.00 (m, 8H), 2.37 (s, 6H), 1.75, 1.90 (each m, 2H). LC/MS 345.0 (M+). 1-propenylamino-3_methoxy-6-benzene Base-2,4-hexyl diol

巾 NMR (CDC13) 7.27 (m，5H)，5.80 (m，1H)，5.15 (m，2Ή)， 4.20(m，1H)，3.50 (s，3H)，3.20-3.45 (m，2H)，2.50-3.00 (m，6H)， 1.75-2.00 (m，2H). LC/MS 280.5 (M++1). 1-(2-二甲胺基乙胺基)-3-甲氧基_6-苯基-2,4-己雙醇 0296-A20652TWF(N2)；323；Uofung 18 1294414NMR (CDC13) 7.27 (m, 5H), 5.80 (m, 1H), 5.15 (m, 2Ή), 4.20 (m, 1H), 3.50 (s, 3H), 3.20-3.45 (m, 2H), 2.50 -3.00 (m, 6H), 1.75-2.00 (m, 2H). LC/MS 280.5 (M++1). 1-(2-dimethylaminoethylamino)-3-methoxy_6- Phenyl-2,4-hexanediol 0296-A20652TWF(N2); 323; Uofung 18 1294414

4 NMR (CDC13) 7.28 (m，5H)，4.25 (m，1H)，3.90 (m，1H)，3.49 (s，3H)，3.25 (m，1H)，2.50-3.00 (m，8H)，2.41 (s，6H)，1.75, 1.90 (each m? 2H). LC/MS 311.0 (M++l). 1-丙烯胺基-6-(3-氣苯基)-3-甲氧基_2,4-己雙醇4 NMR (CDC13) 7.28 (m, 5H), 4.25 (m, 1H), 3.90 (m, 1H), 3.49 (s, 3H), 3.25 (m, 1H), 2.50-3.00 (m, 8H), 2.41 (s,6H), 1.75, 1.90 (each m? 2H). LC/MS 311.0 (M++l). 1-Acrylamino-6-(3-phenylphenyl)-3-methoxy-2- 4-hexyl diol

4 NMR (CDC13) 7.05-7.30 (m，4H)，5.80 (m，1H)，5.33 (m，2H)， 4.13(m，1H)，3.75 (m，lH)，3.50(s，3H)，3.20-3.45 (m，2H)， 2.50-3.00 (m，6H)，1·75·2·00 (m，2H). LC/MS 314.0 (M+). 3-苯甲氧基-1-十二烷胺基-2-己醇4 NMR (CDC13) 7.05-7.30 (m, 4H), 5.80 (m, 1H), 5.33 (m, 2H), 4.13 (m, 1H), 3.75 (m, lH), 3.50 (s, 3H), 3.20 -3.45 (m,2H), 2.50-3.00 (m,6H),1·75·2·00 (m,2H). LC/MS 314.0 (M+). 3-Benzyloxy-1-dodecane Amino-2-hexanol

0296-A20652TWF(N2)；323；Uofung 19 1294414 3-苯甲氧基-1-十二烷胺基-4-甲氧基-2-丁醇0296-A20652TWF(N2); 323; Uofung 19 1294414 3-Benzyloxy-1-dodecylamino-4-methoxy-2-butanol

4 NMR (CDC13) 7.34 (m，5H)，4.76, 4.58 (each m，2H)，3.80 (m， 1H)，3.61 (m，1H)，3·58 (m，2H)，3.38 (s，3H)，2·69 (m，2H)，2.52 (m，2H)，1.43 (m，2H)，1.26 (m，18 H)，0.88 (t，J = 7-1 Hz，1H)· LC/MS 394.5 (M++l). 3 -苯甲氧基-4-甲氧基-1-辛胺基-2-丁醇4 NMR (CDC13) 7.34 (m, 5H), 4.76, 4.58 (each m, 2H), 3.80 (m, 1H), 3.61 (m, 1H), 3·58 (m, 2H), 3.38 (s, 3H) ), 2·69 (m, 2H), 2.52 (m, 2H), 1.43 (m, 2H), 1.26 (m, 18 H), 0.88 (t, J = 7-1 Hz, 1H)· LC/MS 394.5 (M++l). 3-Benzyloxy-4-methoxy-1-octylamino-2-butanol

lU NMR (CDC13) 7.34 (m5 5H)? 4.77? 4.58 (each m? 2H)? 3.80 (m5 1H)，3.62 (m，1H)，3.58 (m，2Ή)，3.38 (s，3H)，2.68 (m，4H)，1.43, 1.28 (each m，12H)，0·88 (t，J = 7.1 Hz，3H)· LC/MS 338.5 (M+)_ 3-苯甲氧基-1-十二烷胺基-2-己醇lU NMR (CDC13) 7.34 (m5 5H)? 4.77? 4.58 (each m? 2H)? 3.80 (m5 1H), 3.62 (m, 1H), 3.58 (m, 2Ή), 3.38 (s, 3H), 2.68 ( m,4H), 1.43, 1.28 (each m,12H),0·88 (t,J = 7.1 Hz,3H)· LC/MS 338.5 (M+)_ 3-Benzyloxy-1-dodecylamine Keto-2-hexanol

NMR (CDCI3) 7.34 (m? 5H)? 4.54, 4.62 (each m? 2H5 isomer ratio 〜2:1)，3.72 (m，1H)，3.38, 3.50 (each m，1H)，2.58, 2.74 (each m，4H)，1.45 (m，4H)，1.26 (m，20H)，0_94 (t，J = 7.4 Hz， 3H)，0.88 (t，J = 7·4 Hz，3H)，，LC/MS 392.5 (M++1). 0296-A20652TWF(N2)；323；Uofung 20 1294414 3 -苯甲氧基-1 -(3 -苯基丙胺基)-2 ·己醇 9 八 c6h5NMR (CDCI3) 7.34 (m? 5H)? 4.54, 4.62 (each m? 2H5 isomer ratio ~2:1), 3.72 (m,1H), 3.38, 3.50 (each m,1H),2.58, 2.74 (each m , 4H), 1.45 (m, 4H), 1.26 (m, 20H), 0_94 (t, J = 7.4 Hz, 3H), 0.88 (t, J = 7.4 Hz, 3H), LC/MS 392.5 ( M++1). 0296-A20652TWF(N2);323;Uofung 20 1294414 3 -Benzyloxy-1 -(3-phenylpropylamino)-2.hexanol 9 octa c6h5

4 NMR (CDC13) 7_27 (m，5H)，7_17 (m，5H)，4.51，4_61 (each m， 2H，isomer ratio 〜4:1)，3·72 (m，1H)，3.38，3.50 (each m，1H)， 2.63-2.74 (m，6H)，1.80 (m，2H)，1.40-1.60 (m，4H)，0.93 (t，J = 7.1 Hz5 3H). LC/MS 342.5 (M++l). 3-苯甲氧基-1-(3-苯基丙胺基)-2-己醇〇八crh54 NMR (CDC13) 7_27 (m, 5H), 7_17 (m, 5H), 4.51, 4_61 (each m, 2H, isomer ratio ～4:1), 3·72 (m, 1H), 3.38, 3.50 (each m,1H), 2.63-2.74 (m,6H), 1.80 (m,2H),1.40-1.60 (m,4H),0.93 (t,J = 7.1 Hz5 3H). LC/MS 342.5 (M++l ). 3-Benzyloxy-1-(3-phenylpropylamino)-2-hexanol 〇 eight crh5

巾 NMR (CDC13) 7.22 (m，5H)，7.11 (m，5H)，4.44, 4.57 (each m， 2H，），3 .63 (m，1H)，3 .25, 3 .38 (each m，1H)，2 .53-2.64 (m，6H)， 1.72 (m，2H)，1.25-1.50 (m，4H)，0.85 (t，J = 7.1 Hz，3H)· LC/MS 342.5 (M+). 3-苯甲氧基-1-(3-苯基丙胺基)-2-己醇氣化氮鹽〇八CfiH5Towel NMR (CDC13) 7.22 (m, 5H), 7.11 (m, 5H), 4.44, 4.57 (each m, 2H,), 3.63 (m, 1H), 3 .25, 3 .38 (each m, 1H), 2. 53-2.64 (m, 6H), 1.72 (m, 2H), 1.25-1.50 (m, 4H), 0.85 (t, J = 7.1 Hz, 3H)· LC/MS 342.5 (M+). 3-Benzyloxy-1-(3-phenylpropylamino)-2-hexanol gasification nitrogen salt 〇8 CfiH5

巾 NMR (CDC13) 7.23, 7.17, 7·07 (each m，10H)，7.11 (m，5H)， 4·47 (s，2H，），3·63 (m，1H)，3.21 (m，1H)，2.64 (m，2H)，2.47-2.56 0296-A20652TWF(N2)；323；Uofung 21 1294414 (m，4H)，1.70 (m，2H)，1.25-1.50 (m，4H)，0·82 (t，J = 7.0 Hz， 3H). 3-苯甲氧基-1-十六烧胺基-4-甲氧基-2-丁醇Towel NMR (CDC13) 7.23, 7.17, 7·07 (each m, 10H), 7.11 (m, 5H), 4·47 (s, 2H,), 3·63 (m, 1H), 3.21 (m, 1H) ), 2.64 (m, 2H), 2.47-2.56 0296-A20652TWF (N2); 323; Uofung 21 1294414 (m, 4H), 1.70 (m, 2H), 1.25-1.50 (m, 4H), 0·82 ( t, J = 7.0 Hz, 3H). 3-Benzyloxy-1-hexadecylamino-4-methoxy-2-butanol

1HNMR(CDCl3)7.34(m?5H)5 4.5 8, 4.74 (each d9 J = 12.0 Ηz? 2H，)，3 .75 (m，1H)，3 .61，3 ·58, 3 _55 (each m，3H)，3.38 (s，3 H)， 2.68, 2.56 (each m，4H)，1.43, 1.28, 0.88 (each m，31H). LC/MS 450.5 (M++l). 3-苯甲氧基-1-十五烷胺基-2-己醇 9 八 c6h51H NMR (CDCl3) 7.34 (m? 5H) 5 4.5 8, 4.74 (each d9 J = 12.0 Ηz? 2H,), 3.75 (m, 1H), 3.61,3 ·58, 3 _55 (each m, 3H), 3.38 (s, 3 H), 2.68, 2.56 (each m, 4H), 1.43, 1.28, 0.88 (each m, 31H). LC/MS 450.5 (M++l). 3-Benzyloxy 1-hexadecanolamino-2-hexanol 9 octa c6h5

NMR (CDC13) 7.34 (m5 5H)? 4.53? 4.63 (each m5 2H1)? 3.72 (m5 1H)，3 .35, 3 ·45 (each m，1Η)，2·58,2·67( each m，4H)，1 .45 (m， 4H)，1.40, 1.28 (each m，30H)，0.93 (t，J = 7·0 Hz，3H)，0.88 (t，J =7.0 Hz? 3H). LC/MS 434.5 (M++l). 3_苯甲氧基-1-十四烷胺基-2-己醇 9 八 c6h5NMR (CDC13) 7.34 (m5 5H)? 4.53? 4.63 (each m5 2H1)? 3.72 (m5 1H), 3.35, 3 ·45 (each m,1Η), 2·58,2·67 (each m, 4H), 1.45 (m, 4H), 1.40, 1.28 (each m, 30H), 0.93 (t, J = 7·0 Hz, 3H), 0.88 (t, J = 7.0 Hz? 3H). LC/ MS 434.5 (M++l). 3_Benzyloxy-1-tetradecylamino-2-hexanol 9 octa c6h5

4 NMR (CDC13) 7.34 (m，5H)，4_53, 4_63 (each m，2H)，3.72 (m， 1H)，3 ·35, 3 ·45 (each m，1Η)，2·58,2·67( each m，4H)，1 .45 (m， 0296-A20652TWF(N2)；323；Uofung 22 1294414 4H)，1.44, 1.26 (each m，28H)，0.93 (t，J = 7·0 Hz，3H)，0·88 (t，J =7.0 Hz5 3H). LC/MS 420.5 (M++l). 3 -苯甲氧基-1-十三娱*胺基_2-己醇4 NMR (CDC13) 7.34 (m,5H),4_53, 4_63 (each m,2H),3.72 (m, 1H),3 ·35, 3 ·45 (each m,1Η),2·58,2·67 ( each m,4H),1 .45 (m, 0296-A20652TWF(N2); 323; Uofung 22 1294414 4H), 1.44, 1.26 (each m, 28H), 0.93 (t, J = 7·0 Hz, 3H ), 0·88 (t, J = 7.0 Hz5 3H). LC/MS 420.5 (M++l). 3-Benzyloxy-1-trioxan*amino-2-hexanol

4 NMR (CDC13) 7.34 (m，5H)，4.53, 4·63 (each m，2H)，3.71 (m， 1H)，3 .35, 3 ·45 (each m，1H)，2.58, 2·67 (each m，4H)，1 ·45 (m， 4H)，1.46, 1.26 (each m，26H)，0-93 (t，J = 7_0 Hz，3H)，0.88 (t，J =7.0 Hz5 3H). LC/MS 406.5 (M++l). 1-十八烷胺基-3十比啶-2-甲氧基)-2-己醇4 NMR (CDC13) 7.34 (m, 5H), 4.53, 4·63 (each m, 2H), 3.71 (m, 1H), 3 .35, 3 · 45 (each m, 1H), 2.58, 2·67 (each m,4H),1 ·45 (m, 4H), 1.46, 1.26 (each m,26H),0-93 (t,J = 7_0 Hz,3H),0.88 (t,J =7.0 Hz5 3H) LC/MS 406.5 (M++l). 1-octadecylamino-3-decabiidine-2-methoxy)-2-hexanol

巾 NMR (CDC13) 8.58, 8·53, 7.58, 7.29 (each m，4H)，4.62 (m， 2H)，3.71 (m，1H)，3.40, 3·50 (each m，1H)，2.67 (m，4H)，2.05 (m， 6H)，1.45 (m，4H)，1.50，1.26 (each m，30H)，0.93 (t，J = 7.0 Hz， 3H)，0.88 (t，J = 7.0 Hz，3H). LC/MS 477_5 (M++1). 1-十八烧胺基-3十比咬_3_甲氧基)-2-己醇Towel NMR (CDC13) 8.58, 8·53, 7.58, 7.29 (each m, 4H), 4.62 (m, 2H), 3.71 (m, 1H), 3.40, 3·50 (each m, 1H), 2.67 (m , 4H), 2.05 (m, 6H), 1.45 (m, 4H), 1.50, 1.26 (each m, 30H), 0.93 (t, J = 7.0 Hz, 3H), 0.88 (t, J = 7.0 Hz, 3H LC/MS 477_5 (M++1). 1-Eoctadecylamine-3-dozen _3_methoxy)-2-hexanol

4 NMR (CDC13) 8.58, 8.52, 7.68, 7_27 (each m，4H)，4.62, 4.69 0296-A20652TWF(N2)；323；Uofung 23 1294414 (each m，2H)，3.71 (m，1H)，3.35，3.50 (each m，1H)，2.67 (m， 4H)，1.45, 1.50 (each m，30H)，0.93 (t，J = 7.0 Hz，3H)，0.88 (t，J =7.0 Hz? 3H). LC/MS 477.5 (M++l). 1-苯甲氧基-3-十八烧胺基-2-丙醇4 NMR (CDC13) 8.58, 8.52, 7.68, 7_27 (each m, 4H), 4.62, 4.69 0296-A20652TWF (N2); 323; Uofung 23 1294414 (each m, 2H), 3.71 (m, 1H), 3.35, 3.50 (each m,1H), 2.67 (m, 4H), 1.45, 1.50 (each m, 30H), 0.93 (t, J = 7.0 Hz, 3H), 0.88 (t, J = 7.0 Hz? 3H). LC /MS 477.5 (M++l). 1-Benzyloxy-3-octadecylamine-2-propanol

4 NMR (CDC13) 7.34 (m，5H)，4.55 (s，2H)，3.80 (m，1H)，3.48 (dd，J = 6.5, 6·1 Hz，1H)，2.58, 2.67 (each m，4H)，1.45 (m，2H)， 1.26 (each m，30H)，0.88 (t，J = 7·1 Hz，3H). LC/MS 434·5 (M++l). 1-苯甲氧基_1·十八烷胺基-2-己醇 9 八 c6h54 NMR (CDC13) 7.34 (m, 5H), 4.55 (s, 2H), 3.80 (m, 1H), 3.48 (dd, J = 6.5, 6·1 Hz, 1H), 2.58, 2.67 (each m, 4H ), 1.45 (m, 2H), 1.26 (each m, 30H), 0.88 (t, J = 7·1 Hz, 3H). LC/MS 434·5 (M++l). 1-Benzyloxy _1·octadecylamino-2-hexanol 9 octa c6h5

4 NMR (CDC13) 7·34 (m，5H)，4.55, 4.63 (each m，2H)，3·72 (m， 1H)，3.35，3.45 (each m，1H)，2.58, 2.67 (each m，4H)，1.44，1.26 (each m，36H)，0.93 (t，J = 7·0 Hz，3H)，0.88 (t，J = 7.0 Hz，3H). LC/MS 476.5 (M++l). 1-辛胺基-3中比啶-2-甲氧基)_2-己醇4 NMR (CDC13) 7·34 (m, 5H), 4.55, 4.63 (each m, 2H), 3·72 (m, 1H), 3.35, 3.45 (each m, 1H), 2.58, 2.67 (each m, 4H), 1.44, 1.26 (each m, 36H), 0.93 (t, J = 7·0 Hz, 3H), 0.88 (t, J = 7.0 Hz, 3H). LC/MS 476.5 (M++l). 1-octylamino-3pyridin-2-methoxy)_2-hexanol

4 NMR (CDC13) 8.58, 8.52, 7.67, 7·27 (each m，4H)，4_62, 4.69 0296-A20652TWF(N2)；323；Uofung 24 1294414 (each m，2H)，3.72 (m，1H)，3.50 (m，1H)，1.89 (m，6H)，2.57, 2.67 (each m，4H)，1.42, 1.50 (each m，16H)，0.93 (t，J = 7.0 Hz， 3H)，0.88 (t，J = 7-0 Hz, 3H)· LC/MS 337.5 (M++1). 1 -己胺基-3 -(11比咬_2 -甲氧基)-2 -己醇4 NMR (CDC13) 8.58, 8.52, 7.67, 7·27 (each m, 4H), 4_62, 4.69 0296-A20652TWF (N2); 323; Uofung 24 1294414 (each m, 2H), 3.72 (m, 1H), 3.50 (m,1H), 1.89 (m,6H), 2.57, 2.67 (each m,4H), 1.42, 1.50 (each m,16H),0.93 (t,J = 7.0 Hz, 3H), 0.88 (t, J = 7-0 Hz, 3H)· LC/MS 337.5 (M++1). 1 -Hexylamino-3 -(11-bite_2-methoxy)-2-hexanol

iH NMR (CDC13) 8.57, 8.53, 7.68, 7.27 (each m，4H)，4.61，4.67 (each m，2H)，3.72 (m，1H)，3.40, 3.50 (each m，1H)，，2.57, 2.67 (each m，4H)，1.30，1-48( each m，6H)，0.93(t，J = 7·0Ηζ，3H)， 0.88 (t5 J = 7.0 Hz? 3H). LC/MS 309.5 (M++l). 1-丁胺基_3-(吡啶-2-甲氧基)-2-己醇iH NMR (CDC13) 8.57, 8.53, 7.68, 7.27 (each m, 4H), 4.61, 4.67 (each m, 2H), 3.72 (m, 1H), 3.40, 3.50 (each m, 1H),, 2.57, 2.67 (each m, 4H), 1.30, 1-48 (each m, 6H), 0.93 (t, J = 7·0Ηζ, 3H), 0.88 (t5 J = 7.0 Hz? 3H). LC/MS 309.5 (M+ +l). 1-butylamino-3-poly(pyridine-2-methoxy)-2-hexanol

巾 NMR (CDC13) 8.50, 8.45, 7.61，7.20 (each m，4H)，4.54, 4.63 (each m，2H)，3 .66 (m，1H)，3 .25, 3 .40 ( each m，1Η)，2.55,2·67 (each m，4H)，1_27，1.38( each m，8H)，0.86(t，J = 7·0Ηζ，3H)， 0.82 (t，J = 7.0 Hz，3H). LC/MS 281.5 (M++1). 1-苯甲氧基-3-辛烷胺基-2-丙醇Towel NMR (CDC13) 8.50, 8.45, 7.61, 7.20 (each m, 4H), 4.54, 4.63 (each m, 2H), 3.66 (m, 1H), 3 .25, 3 .40 (each m, 1Η ), 2.55, 2.67 (each m, 4H), 1_27, 1.38 (each m, 8H), 0.86 (t, J = 7·0Ηζ, 3H), 0.82 (t, J = 7.0 Hz, 3H). LC /MS 281.5 (M++1). 1-Benzyloxy-3-octylamino-2-propanol

0296-A20652TWF(N2)；323；Uofung 25 1294414 * lU NMR (CDC13) 7.37 (m5 5H), 4.59 (s? 2H)? 3.90 (m5 1H)? 3.52 (dd，J = 7.0, 6.5 Hz，2H)，2.50-2.75 (m，4H)，1.50 (m，2H)，1.34 (m，2H)，0_91 (t，J = 7.1 Hz，3H)，0.82 (t，J = 7_0 Hz，3H)· LC/MS 294.5 (M++l). 1 -苯甲氧基-3 -(3 ·二甲胺基丙胺基）-2 -丙醇 H3C、n 八。此0296-A20652TWF(N2); 323; Uofung 25 1294414 * lU NMR (CDC13) 7.37 (m5 5H), 4.59 (s? 2H)? 3.90 (m5 1H)? 3.52 (dd, J = 7.0, 6.5 Hz, 2H) , 2.50-2.75 (m, 4H), 1.50 (m, 2H), 1.34 (m, 2H), 0_91 (t, J = 7.1 Hz, 3H), 0.82 (t, J = 7_0 Hz, 3H)· LC/ MS 294.5 (M++1). 1-Benzyloxy-3-(3.dimethylaminopropylamino)-2-propanol H3C, n. this

ch3 h OH 此化合物由3-二甲胺基丙胺及〇SH+)-2-苯甲氧基甲基環氧乙烷所合成。咕 NMR (CDC13) 7_34 (m，5H)，4_55 (s，2H)，3·90 (m，1H)，3.48 (m，3Hz)，2.50-2.75 (m，4H)，1_50 (m，2H)，2.40 (m，2H)，2·21 (s， 6H). 1-苯甲氧基-3-(3-二甲胺基丙胺基）-2-丙醇八丫〜〇八。6|_!5Ch3 h OH This compound was synthesized from 3-dimethylaminopropylamine and hydrazine SH+)-2-benzyloxymethyloxirane.咕NMR (CDC13) 7_34 (m,5H),4_55 (s,2H),3·90 (m,1H), 3.48 (m,3Hz), 2.50-2.75 (m,4H),1_50 (m,2H) , 2.40 (m, 2H), 2·21 (s, 6H). 1-Benzyloxy-3-(3-dimethylaminopropylamino)-2-propanol octadecyl-8. 6|_!5

CH3 h OH 此化合物由3-二甲胺基丙胺及（72)-(-)-2-苯甲氧基甲基環氧乙烷所合成。 lU NMR (CDCI3) 7.33 (m? 5H)? 4.55 (s? 2H)? 3.90 (m? 1H)? 3.48 (m，2Hz)，2·50-2·75 (m，4H)，1.50 (m，2H)，2.40 (m，2H)，2·21 (s， 6H). 1-(3 _苯基丙胺基）_3 -(吨啶-2_甲氧基)-2 _己醇 0296-A20652TWF(N2)；323；Uofung 26 1294414CH3 h OH This compound was synthesized from 3-dimethylaminopropylamine and (72)-(-)-2-benzylmethoxymethyloxirane. lU NMR (CDCI3) 7.33 (m? 5H)? 4.55 (s? 2H)? 3.90 (m? 1H)? 3.48 (m, 2Hz), 2·50-2·75 (m, 4H), 1.50 (m, 2H), 2.40 (m, 2H), 2·21 (s, 6H). 1-(3 _Phenylpropylamino)_3 -(t-pyridine-2-methoxy)-2-hexanol 0296-A20652TWF( N2); 323; Uofung 26 1294414

4 NMR (CDC13) 8.48 (m，1H)，8.43 (m，1Η)，7.59 (m，1Η)，7·18 (m，3H)，7.09 (m，3H)，4.52，4.58 (each m，2H)，3.66 (m，1H)， 3.25, 3.40 (each m，1H)，2.50 (m，6H)，1.25-1.50 (m，4H)，0.83 (t， J = 7·1 Hz，3H)，0.82 (t，J = 7.0 Hz，3H)· LC/MS 343·5 (M++1). 1 -十二烧胺基-3 _ (0比咬-2 -甲氧基)-2 _己醇4 NMR (CDC13) 8.48 (m,1H), 8.43 (m,1Η), 7.59 (m,1Η),7·18 (m,3H),7.09 (m,3H),4.52,4.58 (each m,2H ), 3.66 (m, 1H), 3.25, 3.40 (each m, 1H), 2.50 (m, 6H), 1.25-1.50 (m, 4H), 0.83 (t, J = 7·1 Hz, 3H), 0.82 (t, J = 7.0 Hz, 3H)· LC/MS 343·5 (M++1). 1 - dodecylamine-3 _ (0 ratio bit-2-methoxy)-2 _hexanol

NMR (CDC13) 8.58 (m? 1H)5 8.54 (m5 1H)? 7.69 (m? 1H)? 7.28 (m，1H)，4·65 (m，2H)，3.74 (m，1H)，3·40, 3.50 (each m，1H)， 2.63, 2·66 (each m，4H)，1.28，1_46 (each m，22H)，0.93 (t，J = 7.1 Hz，3H)，0.88 (t，J = 7_1 Hz，3H)· LC/MS 392.5 (M+). 1 -己娱》胺基-3 -(11比咬_3 _甲氧基)_2 己醇NMR (CDC13) 8.58 (m? 1H)5 8.54 (m5 1H)? 7.69 (m? 1H)? 7.28 (m,1H),4·65 (m,2H), 3.74 (m,1H),3·40 , 3.50 (each m,1H), 2.63, 2·66 (each m,4H),1.28,1_46 (each m,22H),0.93 (t,J = 7.1 Hz,3H),0.88 (t,J = 7_1 Hz,3H)· LC/MS 392.5 (M+). 1 - Entertainment" Amino-3 - (11 ratio bite_3 _methoxy)_2 hexanol

巾 NMR (CDC13) 8.57 (m，1H)，8·53 (m，1H)，7_68 (m，1H)，7·27 (m，1H)，4.64 (m，2H)，3_71 (m，1H)，3.40, 3.50 (each m，1H)， 2·50_2·70 (each m，4H)，1.47 (m，6H)，1.31 (m，6H)，0·94 (t，J = 7.0 Hz，3H)，0.88 (t，J = 7.0 Hz，3H). LC/MS 309.5 (M++1). 0296-A20652TWF(N2)；323；Uofung 27 1294414 1 _ 丁烧胺基_3 -(σ比咬-3 _甲氧基)-2 -己醇NMR (CDC13) 8.57 (m,1H),8·53 (m,1H),7_68 (m,1H),7·27 (m,1H),4.64 (m,2H),3_71 (m,1H) , 3.40, 3.50 (each m, 1H), 2·50_2·70 (each m, 4H), 1.47 (m, 6H), 1.31 (m, 6H), 0·94 (t, J = 7.0 Hz, 3H) , 0.88 (t, J = 7.0 Hz, 3H). LC/MS 309.5 (M++1). 0296-A20652TWF (N2); 323; Uofung 27 1294414 1 _ butyl amine base _3 - (σ ratio bite - 3 _Methoxy)-2-hexanol

巾 NMR (CDC13) 8_50 (m，1H)，8.45 (m，1H)，7.60 (m，1H)，7.20 (m，1H)，4.53, 4.64 (each m5 2H)，3.65 (m，1H)，3.25, 3.40 (each m，1H)，2.50-2.70 (each m，4H)，1.20-1.40 (m，8H)，0.86 (t，J = 7.0 Hz，3H)，0·82 (t，J = 7.0 Hz，3H)· LC/MS 281.5 (M++1). 1_(3-苯基丙胺基）-3-(。比啶-3-甲氧基)-2-己醇Towel NMR (CDC13) 8_50 (m, 1H), 8.45 (m, 1H), 7.60 (m, 1H), 7.20 (m, 1H), 4.53, 4.64 (each m5 2H), 3.65 (m, 1H), 3.25 , 3.40 (each m,1H), 2.50-2.70 (each m,4H),1.20-1.40 (m,8H),0.86 (t,J = 7.0 Hz,3H),0·82 (t,J = 7.0 Hz ,3H)· LC/MS 281.5 (M++1). 1_(3-Phenylpropylamino)-3-(.pyridin-3-methoxy)-2-hexanol

lR NMR (CDC13) 8.49 (m5 1H)5 8.43 (m5 1H)? 7.59 (m5 1H)5 7.18 (m，1H)，7.09 (m，3H)，4.52, 4_59 (each m，2H)，3.66 (m，1H)，3.25, 3.40 (each m，1H)，2.50-2.70 (m，6H)，1.20-1.50 (m，4H)，0.84 (t， J = 7.0 Hz? 3H). LC/MS 343.5 (M++l). 1_十六烷胺基-3-(吡啶-3-甲氧基)-2-己醇lR NMR (CDC13) 8.49 (m5 1H)5 8.43 (m5 1H)? 7.59 (m5 1H)5 7.18 (m,1H),7.09 (m,3H),4.52, 4_59 (each m,2H),3.66 (m , 1H), 3.25, 3.40 (each m, 1H), 2.50-2.70 (m, 6H), 1.20-1.50 (m, 4H), 0.84 (t, J = 7.0 Hz? 3H). LC/MS 343.5 (M ++l). 1_hexadecaneamino-3-(pyridine-3-methoxy)-2-hexanol

!H NMR (CDCI3) 8.57 (m? 1H)? 8.52 (m5 1H)5 7.65 (m? 1H)? 6.90 (s，1H)，4.52 (m，2H)，3.65 (m，1H)，3.25, 3.40 (each m，1H)，3.12 (m，4H)，1.20-1.70 (m，30H)，0.86 (t，J = 7.0 Hz，3H). 0.81 (t，J = 7.0 Hz, 3H). LC/MS 449.5 (M++l). 0296-A20652TWF(N2)；323；Uofung 28 1294414 1-十二烷胺基_3十比啶-3-甲氧基)-2_己醇!H NMR (CDCI3) 8.57 (m? 1H)? 8.52 (m5 1H)5 7.65 (m? 1H)? 6.90 (s,1H), 4.52 (m,2H), 3.65 (m,1H), 3.25, 3.40 (each m,1H),3.12 (m,4H),1.20-1.70 (m,30H),0.86 (t,J = 7.0 Hz,3H). 0.81 (t,J = 7.0 Hz, 3H). LC/MS 449.5 (M++l). 0296-A20652TWF(N2); 323; Uofung 28 1294414 1-dodecylamine _3 decapyridin-3-methoxy)-2-hexanol

4 NMR (CDC13) 8.57 (m，1H)，8.52 (m，1H)，7.19 (m，1H)，6.90 (s，1H)，4.56 (m，2H)，3.65 (m，1H)，3.20, 3.40 (each m，1H)，3·12 (m，4H)，1.20-1.70 (m，24H)，0.86 (t，J = 7.0 Hz，3H)· 0.81 (t，J = 7.0 Hz5 3H). LC/MS 393.5 (M++l). 1-苯甲氧基-3-(4-三氟甲基苯胺基）_2-丙醇4 NMR (CDC13) 8.57 (m, 1H), 8.52 (m, 1H), 7.19 (m, 1H), 6.90 (s, 1H), 4.56 (m, 2H), 3.65 (m, 1H), 3.20, 3.40 (each m,1H),3·12 (m,4H),1.20-1.70 (m,24H),0.86 (t,J = 7.0 Hz,3H)· 0.81 (t,J = 7.0 Hz5 3H). LC/ MS 393.5 (M++l). 1-Benzyloxy-3-(4-trifluoromethylanilino)_2-propanol

lU NMR (CDC13) 7.20-7.35 (m? 7H)5 6.53 (d? J = 7.0 Hz? 1H), 4.50 (s，2H)，4.00 (m，1H)，3.54 (m，1H)，3.45 (m，1H)，3.25 (m， 1H). LC/MS 326.0 (M++l). 1-苯甲氧基-3-庚胺基-2-丙醇lU NMR (CDC13) 7.20-7.35 (m? 7H)5 6.53 (d? J = 7.0 Hz? 1H), 4.50 (s, 2H), 4.00 (m, 1H), 3.54 (m, 1H), 3.45 (m , 1H), 3.25 (m, 1H). LC/MS 326.0 (M++1). 1-Benzyloxy-3-heptylamino-2-propanol

lR NMR (CDCI3) 7.36 (m5 5H)5 4.58 (s5 2H)? 3.54 (m? 1H)? 3.72 (m，1H)，3.51 (dd，J = 7·0, 6·5 Hz，2H)，2.50-2.70 (m，4H)，1.47 (m，2H)，1.32 (m，8H)，0.91 (t，J = 7.0 Hz，3H)·. LC/MS 280.5 (M++l). 0296-A20652TWF(N2)；323；Uofung 29 1294414 1-苯甲氧基-3-戊胺基-2-丙醇lR NMR (CDCI3) 7.36 (m5 5H)5 4.58 (s5 2H)? 3.54 (m? 1H)? 3.72 (m,1H), 3.51 (dd, J = 7·0, 6·5 Hz, 2H), 2.50 -2.70 (m, 4H), 1.47 (m, 2H), 1.32 (m, 8H), 0.91 (t, J = 7.0 Hz, 3H)·. LC/MS 280.5 (M++l). 0296-A20652TWF ( N2); 323; Uofung 29 1294414 1-Benzyloxy-3-pentylamino-2-propanol

lR NMR (CDC13) 7.36 (m5 5H)? 4.57 (s? 2H)? 3.54 (m? 1H)5 3.88 (m，1H)，3.40-3.55 (m，2H)，2.50-2.80 (m，4H)，1.50 (m，2H)， 1.31 (m，4H)，0.91 (t，J = 7.0 Hz，3H)· LC/MS 252·5 (M++1). 2-苯甲氧基-1-庚胺基-2-己醇 9 八 c6h5lR NMR (CDC13) 7.36 (m5 5H)? 4.57 (s? 2H)? 3.54 (m? 1H)5 3.88 (m,1H), 3.40-3.55 (m,2H), 2.50-2.80 (m,4H), 1.50 (m, 2H), 1.31 (m, 4H), 0.91 (t, J = 7.0 Hz, 3H)· LC/MS 252·5 (M++1). 2-Benzyloxy-1-heptylamine Base-2-hexanol 9 八c6h5

巾 NMR (CDC13) 7_27 (m，5H)，4·48, 4_57 (each m，2H)，3.52 (m， 1H)，3_88 (m，1H)，3.25, 3·40 (each m，1H)，1.25-1.50 (m，6H)， 1.20 (m，8H)，0·87 (t，J = 7·0 Hz，3H)，0·81 (t，J = 7.0 Hz，3H). LC/MS 322.5 (M++l). 3-苯甲氧基-1-戊胺基-2-己醇 9 八 c6H5Towel NMR (CDC13) 7_27 (m, 5H), 4·48, 4_57 (each m, 2H), 3.52 (m, 1H), 3_88 (m, 1H), 3.25, 3·40 (each m, 1H), 1.25-1.50 (m,6H), 1.20 (m,8H),0·87 (t,J = 7·0 Hz, 3H), 0·81 (t, J = 7.0 Hz, 3H). LC/MS 322.5 (M++l). 3-Benzyloxy-1-pentylamino-2-hexanol 9 octa c6H5

咕 NMR (CDC13) 7.27 (m，5H)，4.47, 4.57 (each m，2H)，3.66 (m， 1H)，3.25, 3.40 (each m，1H)，2·50·2·70 (m，4H)，1.20-1.50 (m， 10H)，0.87 (t，J = 7·0 Hz，3H)，0.82 (t，J = 7.0 Hz，3H). LC/MS 294·5 (M++1). 3-苯甲氧基_1_十六烷胺基-2-己醇 0296-A20652TWF(N2)；323；Uofung 30 1294414 9 八 c6h5咕NMR (CDC13) 7.27 (m,5H), 4.47, 4.57 (each m,2H),3.66 (m, 1H), 3.25, 3.40 (each m,1H),2·50·2·70 (m,4H ), 1.20 - 1.50 (m, 10H), 0.87 (t, J = 7·0 Hz, 3H), 0.82 (t, J = 7.0 Hz, 3H). LC/MS 294·5 (M++1). 3-benzyloxy_1_hexadecylamino-2-hexanol 0296-A20652TWF (N2); 323; Uofung 30 1294414 9 oc c6h5

4 NMR (CDC13) 7_36 (m，5H)，4·57, 4.67 (each m，2H)，3_74 (m， 1H)，3.40, 3.50 (each m，1H)，2_50_2·70 (m，4H)，1.50-1.70 (m， 6H)，1.27 (m，26H)，0.96 (t，J = 7.0 Hz，3H)，0.91 (t，J = 7.0 Hz， 3H). LC/MS 448.5 (M++l). 3-苯甲氧基-1-十二烷胺基-2-己醇4 NMR (CDC13) 7_36 (m, 5H), 4·57, 4.67 (each m, 2H), 3_74 (m, 1H), 3.40, 3.50 (each m, 1H), 2_50_2·70 (m, 4H), 1.50-1.70 (m, 6H), 1.27 (m, 26H), 0.96 (t, J = 7.0 Hz, 3H), 0.91 (t, J = 7.0 Hz, 3H). LC/MS 448.5 (M++l) 3-Benzyloxy-1-dodecylamino-2-hexanol

咕 NMR (CDC13) 7.43 (m，5H)，4.64, 4.71 (each m，2H)，3.74 (m， 1H)，4·21 (m，1H)，3_50 (m，1H)，2.55-2-90 (m，4H)，1·50_1·75 (m， 6H)，1.36 (m，18H)，1.03 (t，J = 7.0 Hz，3H)，0.98 (t，J = 7.0 Hz， 3H). LC/MS 392.5 (M++l). 3-苯甲氧基-1-辛胺基-2-己醇 9 八 c6H5咕NMR (CDC13) 7.43 (m,5H), 4.64, 4.71 (each m,2H), 3.74 (m, 1H),4·21 (m,1H),3_50 (m,1H),2.55-2-90 (m, 4H), 1·50_1·75 (m, 6H), 1.36 (m, 18H), 1.03 (t, J = 7.0 Hz, 3H), 0.98 (t, J = 7.0 Hz, 3H). LC/ MS 392.5 (M++l). 3-Benzyloxy-1-octylamino-2-hexanol 9 octa c6H5

4 NMR (CDC13) 7.36 (m，5H)，4.56, 4.65 (each m，2H)，3.77 (m， 1H)，3.40, 3·50 (each m，1H)，3.50 (m，1H)，2.50-2.70 (m，4H)， 1.50-1.75 (m，6H)，1.31 (m，10H)，0.96(t，J = 7·0 Hz，3H)，0.91 (t， J = 7.0 Hz, 3H). LC/MS 336.5 (M++1). 3-苯甲氧基-1-丁基乙胺基-2 _己醇 0296-A20652TWF(N2)；323；Uofung 31 1294414 ?八。6叱4 NMR (CDC13) 7.36 (m, 5H), 4.56, 4.65 (each m, 2H), 3.77 (m, 1H), 3.40, 3·50 (each m, 1H), 3.50 (m, 1H), 2.50- 2.70 (m, 4H), 1.50-1.75 (m, 6H), 1.31 (m, 10H), 0.96 (t, J = 7·0 Hz, 3H), 0.91 (t, J = 7.0 Hz, 3H). LC /MS 336.5 (M++1). 3-Benzyloxy-1-butylethylamino-2-hexanol 0296-A20652TWF (N2); 323; Uofung 31 1294414 ? 6叱

OH 4 NMR (CDC13) 7·28 (m，5H)，4.57 (s，2H)，3.55 (m，1H)，3_25 (m, 1H)，2.55 (m，1H)，2_42 (m，3H)，2.33 (m，1H)，1·25·1·60 (m， 8H)，0.94 (t，J = 7.0 Hz，3H)，0.84 (t，J = 7.0 Hz，3H)· LC/MS 308.5 (M++l). 3 -苯甲氧基-1-丁基甲胺基-2-己醇〇^c6h5OH 4 NMR (CDC13) 7·28 (m, 5H), 4.57 (s, 2H), 3.55 (m, 1H), 3_25 (m, 1H), 2.55 (m, 1H), 2_42 (m, 3H), 2.33 (m,1H),1·25·1·60 (m, 8H), 0.94 (t, J = 7.0 Hz, 3H), 0.84 (t, J = 7.0 Hz, 3H)· LC/MS 308.5 (M ++l). 3-Benzyloxy-1-butylmethylamino-2-hexanol 〇^c6h5

I OH !H NMR (CDC13) 7.37 (m5 5H)? 4.67 (s? 2H)? 3.75 (m? 1H)? 3.40 (m，1H)，2.50 (m，2H)，2.25-2.40 (m，5H)，1.40-1.75 (m，8H)， 0.95 (t5 J = 7.0 Hz? 3H)? 0.92 (t? J = 7.0 Hz5 3H). LC/MS 294.5 (M++1)· 1-苯甲氧基_3-丁基甲胺基-2-丙醇I OH !H NMR (CDC13) 7.37 (m5 5H)? 4.67 (s? 2H)? 3.75 (m? 1H)? 3.40 (m, 1H), 2.50 (m, 2H), 2.25-2.40 (m, 5H) , 1.40 - 1.75 (m, 8H), 0.95 (t5 J = 7.0 Hz? 3H)? 0.92 (t? J = 7.0 Hz5 3H). LC/MS 294.5 (M++1)· 1-Benzyloxy_ 3-butylmethylamino-2-propanol

八γ^〇八 c6h5 1 OH ^ NMR (CDC13) 7.34 (m，5H)，4.58 (s，2H)，3.80 (m，1H)，3.48 (m，3H)，2.46 (m，2H)，2.36 (m，2H)，2.26 (s，3H)，1.48 (m，2H)， 1.33 (m，2H)，0.91 (t，J = 7·0 Hz，3H)· LC/MS 252.5 (M++1). 1-苯甲氧基-3-十六烷胺基-2-丙醇八 c6h5八 γ 〇 c c6h5 1 OH ^ NMR (CDC13) 7.34 (m, 5H), 4.58 (s, 2H), 3.80 (m, 1H), 3.48 (m, 3H), 2.46 (m, 2H), 2.36 ( m, 2H), 2.26 (s, 3H), 1.48 (m, 2H), 1.33 (m, 2H), 0.91 (t, J = 7·0 Hz, 3H)· LC/MS 252.5 (M++1) . 1-Benzyloxy-3-hexadecylamino-2-propanol octa c6h5

OH 0296-A20652TWF(N2)；323；Uofung 32 1294414 · 4 NMR (CDC13) 7.34 (m，5H)，4·56 (s，2H)，3.80 (m，1Η)，3·48 (m，3H)，2.50-2.75 (m，4H)，1.50 (m，2H)，1.26 (m，26H)，0.90 (t5 J = 7.0 Hz? 3H). LC/MS 406.5 (M++l). 1·苯甲氧基-3-十二烷胺基-2-丙醇OH 0296-A20652TWF(N2); 323; Uofung 32 1294414 · 4 NMR (CDC13) 7.34 (m, 5H), 4·56 (s, 2H), 3.80 (m, 1 Η), 3·48 (m, 3H) , 2.50-2.75 (m, 4H), 1.50 (m, 2H), 1.26 (m, 26H), 0.90 (t5 J = 7.0 Hz? 3H). LC/MS 406.5 (M++l). Oxy-3-dodecylamino-2-propanol

咕 NMR (CDC13) 7.33 (m，5H)，4.56 (s，2H)，3.80 (m，1H)，3·49 (m，3Η)，2_50·2_75 (m，4Η)，1.48 (m，2Η)，1·27 (m，18Η)，0·87 (t， J = 7.0 Ηζ，3Η). LC/MS 350.5 (Μ++1). 3-苯甲氧基-1-丁基乙胺基-2-戊醇咕NMR (CDC13) 7.33 (m,5H), 4.56 (s,2H), 3.80 (m,1H),3·49 (m,3Η), 2_50·2_75 (m,4Η), 1.48 (m,2Η) ,1·27 (m,18Η),0·87 (t, J = 7.0 Ηζ,3Η). LC/MS 350.5 (Μ++1). 3-Benzyloxy-1-butylethylamino- 2-pentanol

!H NMR (CDC13) 7.33 (m5 5H)5 4.62-4.65 (m? 2H)5 3.46? 3.71 (each m，2 H)，2.38-2.64 (m，6H)，1.25-1.75 (m，6H)，1.02 (t，J = 7.0 Hz，3H)，0.99 (t，J = 7.0 Hz，3H). 0·89 (t，J = 7.0 Hz，3H). 3-苯甲氧基-1-丁基甲胺基-2-戊醇!H NMR (CDC13) 7.33 (m5 5H)5 4.62-4.65 (m? 2H)5 3.46? 3.71 (each m,2 H), 2.38-2.64 (m,6H),1.25-1.75 (m,6H), 1.02 (t, J = 7.0 Hz, 3H), 0.99 (t, J = 7.0 Hz, 3H). 0·89 (t,J = 7.0 Hz, 3H). 3-Benzyloxy-1-butylmethylamino -2-pentanol

咕 NMR (CDC13) 7.33 (m，5H)，4.56-4.65(m，2H)，3·46，3.75 (each m，2 H)，2.23-2.52 (m，4H)，2.22 (s，3H)，1.50-1.75 (m，2H)， 0296-A20652TWF(N2)；323；Uofung 33 1294414 0.95-1.50 (m，4H)，0.97(t，J =7.0 Ηζ，3Η)·0·89 (t，J =7.0 Hz， 3H). 2 _苯甲氧基-3 - 丁基乙胺基_2 -丙醇咕NMR (CDC13) 7.33 (m, 5H), 4.56-4.65 (m, 2H), 3·46, 3.75 (each m, 2 H), 2.23-2.52 (m, 4H), 2.22 (s, 3H), 1.50-1.75 (m, 2H), 0296-A20652TWF (N2); 323; Uofung 33 1294414 0.95-1.50 (m, 4H), 0.97 (t, J = 7.0 Ηζ, 3 Η) · 0·89 (t, J = 7.0 Hz, 3H). 2 _Benzyloxy-3 - butylethylamino-2-propanol

此化合物由丁基乙基胺及〇SH+)-2-苯甲氧基曱基環氧乙烷所合成。巾 NMR (CDC13) 7.33 (m，5H)，4.56 (s，2H)，3.82 (m，1H)，3_49 (m，2 H)，2.61 (m，1H)，2·40_2_50 (m，5H)，1.43 (m，2H)，1.30 (m， 2H)，1.02 (t，J = 7.0 Hz，3H)，0.90 (t，J = 7·0 Hz，3H). 3·苯甲氧基-3-丁基乙胺基-2-丙醇This compound was synthesized from butylethylamine and hydrazine SH+)-2-benzyloxyindenyl oxirane. NMR (CDC13) 7.33 (m, 5H), 4.56 (s, 2H), 3.82 (m, 1H), 3_49 (m, 2 H), 2.61 (m, 1H), 2·40_2_50 (m, 5H), 1.43 (m, 2H), 1.30 (m, 2H), 1.02 (t, J = 7.0 Hz, 3H), 0.90 (t, J = 7·0 Hz, 3H). 3. Benzyloxy-3-butene Ethylamino-2-propanol

此化合物由丁基乙基胺及苯甲氧基甲基環氧乙烷所合成。 lU NMR (CDC13) 7.33 (m5 5H)5 4.56 (s5 2H)? 3.82 (m? 1H)5 3.49 (m，2 H)，2.61 (m，1H)，2.40-2.50 (m，5H)，1.43 (m，2H)，1.30 (m， 2H)，1.02 (t，J = 7.0 Hz，3H)，0.90 (t，J = 7.0 Hz，3H). 1-(2 •二甲基胺乙基胺)·3-(2 -硝基苯甲氧基)-2 ·丙醇This compound is a combination of butylethylamine and benzyloxymethyloxirane. lU NMR (CDC13) 7.33 (m5 5H)5 4.56 (s5 2H)? 3.82 (m? 1H)5 3.49 (m,2 H), 2.61 (m,1H), 2.40-2.50 (m,5H), 1.43 ( m, 2H), 1.30 (m, 2H), 1.02 (t, J = 7.0 Hz, 3H), 0.90 (t, J = 7.0 Hz, 3H). 1-(2 • dimethylamine ethylamine) 3-(2-nitrobenzyloxy)-2·propanol

0296-A20652TWF(N2)；323；Uofung 34 1294414 4 NMR (CDC13) 8.13 (m，1H)，8.08 (d，J = 8·0 Hz，1H)，7.60 (d， J = 8.0 Hz，1H)，7.45 (m，1H)，4.59 (s，2H)，3.25-3.50 (m，3H)， 2.50-3.00 (m，6 H)，2.26 (s，6H)· 1-(2-二丁基胺乙基胺）-3-(2-硝基苯甲氧基）-2-丙醇0296-A20652TWF(N2); 323; Uofung 34 1294414 4 NMR (CDC13) 8.13 (m, 1H), 8.08 (d, J = 8·0 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.45 (m,1H), 4.59 (s,2H), 3.25-3.50 (m,3H), 2.50-3.00 (m,6 H), 2.26 (s,6H)· 1-(2-dibutylamine B Alkyl)-3-(2-nitrobenzyloxy)-2-propanol

lH NMR (CDCls) 8.22 (m? 1H)? 8.15 (d5 J = 8.1 Hz? 1H)5 7.69 (d? J = 8.1 Hz，1H)，7.52 (m，1H)，4.68 (s，2H)，3.95 (m，1H)，3.55(m， 2H)，2.40-2.75 (m，6 H)，1.25-1.50 (m，8H)，0.93 (t，J = 7.0 Hz， 3H)? 0.90 (t? J = 7.0 Hz5 3H). 1-(2-二甲基胺乙基胺）-3-(2-硝基苯甲氧基）-2-丙醇lH NMR (CDCls) 8.22 (m? 1H)? 8.15 (d5 J = 8.1 Hz? 1H)5 7.69 (d? J = 8.1 Hz, 1H), 7.52 (m, 1H), 4.68 (s, 2H), 3.95 (m, 1H), 3.55 (m, 2H), 2.40-2.75 (m, 6 H), 1.25-1.50 (m, 8H), 0.93 (t, J = 7.0 Hz, 3H)? 0.90 (t? J = 7.0 Hz5 3H). 1-(2-Dimethylaminoethylamine)-3-(2-nitrobenzyloxy)-2-propanol

NMR (CDC13) 8.14 (m，1H)，8.08 (d，J = 8·0 Hz, 1H)，7.60 (d， J = 8·0 Hz，1H)，7.45 (m，1H)，4.59 (s，2H)，3.25-3.75 (m，3H)， 2.40-2.90 (m, 6H)，2.28 (s，6H)· 1-(2-二丁基胺乙基胺）-3-(3-硝基苯甲氧基）-2-丙醇NMR (CDC13) 8.14 (m, 1H), 8.08 (d, J = 8·0 Hz, 1H), 7.60 (d, J = 8·0 Hz, 1H), 7.45 (m, 1H), 4.59 (s, 2H), 3.25-3.75 (m, 3H), 2.40-2.90 (m, 6H), 2.28 (s, 6H)· 1-(2-dibutylamineethylamine)-3-(3-nitrobenzene Methoxy)-2-propanol

4 NMR (CDC13) 8.25 (m，1H)，8.21 (d，J = 8·0 Ηζ，1Η)，7.67 (d， J = 8.0 Hz，1H)，7.52 (m，1H)，4.68 (s，2H)，3.95 (m，1H)，3·54 (m， 0296-A20652TWF(N2)；323；Uofung 35 1294414 2H)，2·30_2·75 (m，6H)，1.25-1.50 (m，8H)，0·94 (t，J = 7·0 Hz， 3H)，0.90 (t，J = 7.0 Hz，3H).......... 1-(丁基乙胺基）-3-(2-硝基苯甲氧基）-2-丙醇4 NMR (CDC13) 8.25 (m, 1H), 8.21 (d, J = 8·0 Ηζ, 1Η), 7.67 (d, J = 8.0 Hz, 1H), 7.52 (m, 1H), 4.68 (s, 2H) ), 3.95 (m, 1H), 3·54 (m, 0296-A20652TWF (N2); 323; Uofung 35 1294414 2H), 2·30_2·75 (m, 6H), 1.25-1.50 (m, 8H), 0·94 (t, J = 7·0 Hz, 3H), 0.90 (t, J = 7.0 Hz, 3H)........ 1-(butylethylamino)-3-( 2-nitrobenzyloxy)-2-propanol

lU NMR (CDCls) 8.30 (m? 1H)? 8.22 (d3 J = 8.0 Hz? 1H)? 7.77 (d? J = 8.0 Hz，1H)，7.61 (m，1H)，4.76 (s，2H)，3.95 (m，1H)，3.64 (m， 2H)5 2.50-2.85 (m? 6H)? 1.50-1.60 (m，2H)，1.30-1.50 (m，2H)， 1.14(t5 J = 7.0 Hz? 3H)? 1.00 (t5 J = 7.0 Hz, 3H). 1-丙烯胺基-3-(2-硝基苯甲氧基）-2-丙醇lU NMR (CDCls) 8.30 (m? 1H)? 8.22 (d3 J = 8.0 Hz? 1H)? 7.77 (d? J = 8.0 Hz, 1H), 7.61 (m, 1H), 4.76 (s, 2H), 3.95 (m,1H), 3.64 (m, 2H)5 2.50-2.85 (m? 6H)? 1.50-1.60 (m, 2H), 1.30-1.50 (m, 2H), 1.14 (t5 J = 7.0 Hz? 3H) 1.00 (t5 J = 7.0 Hz, 3H). 1-Propanylamino-3-(2-nitrobenzyloxy)-2-propanol

4 NMR (CDC13) 8.20 (m, 1H)，8.15 (d，J = 8.0 Hz，1H)，7.67 (d， J = 8.0 Hz，1H)，7.53 (m，1H)，5.95 (m，1H)，5.20 (m，2H)，4.00, 4.25 (each m，1H)，3.50 (m，2H)，3.35 (m，2H)，2.70-2.85 (m， 2H). 1-(丁基甲胺基）-3-(2-硝基苯甲氧基）-2-丙醇4 NMR (CDC13) 8.20 (m, 1H), 8.15 (d, J = 8.0 Hz, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.53 (m, 1H), 5.95 (m, 1H), 5.20 (m, 2H), 4.00, 4.25 (each m, 1H), 3.50 (m, 2H), 3.35 (m, 2H), 2.70-2.85 (m, 2H). 1-(butylmethylamino)-3- (2-nitrobenzyloxy)-2-propanol

lU NMR (CDCls) 8.25 (m? 1H)? 8.22 (d? J = 8.0 Hz3 1H)? 7.66 (d? J = 8.0 Hz，1H)，7.53 (m，1H)，4.47 (s，2H)，3.95 (m，1H)，3.56 (m， 0296-A20652TWF(N2)；323；Uofung 36 1294414 2H)，2.60 (m，2H)，2·50 (m，2H)，2.37 (s，3H)，1.51 (m5 2H)，1·33 (m，2H)，0·92 (t，J = 7.0 Hz，3H). 1-(丁基乙胺基）-3-(3-硝基苯甲氧基）-2-丙醇lU NMR (CDCls) 8.25 (m? 1H)? 8.22 (d? J = 8.0 Hz3 1H)? 7.66 (d? J = 8.0 Hz, 1H), 7.53 (m, 1H), 4.47 (s, 2H), 3.95 (m, 1H), 3.56 (m, 0296-A20652TWF (N2); 323; Uofung 36 1294414 2H), 2.60 (m, 2H), 2·50 (m, 2H), 2.37 (s, 3H), 1.51 ( M5 2H),1·33 (m,2H),0·92 (t,J = 7.0 Hz, 3H). 1-(butylethylamino)-3-(3-nitrobenzyloxy)- 2-propanol

lH NMR (CDC13) 8.30 (m? 1H)? 8.22 (d? J = 8.0 Hz? 1H)? 7.77 (d5 J = 8.0 Hz，1H)，7.61 (m，1H)，4·76 (s，2H)，3.99 (m，1H)，3.64 (m， 2H)，2.50-2.80 (m，6H)，1.54 (m，2H)，1.39 (m，2H)，1.14 (t，J = 7·0 Hz，3H)，1.00 (t，J = 7.0 Hz，3H)· 1-丙烯胺基-3-(3-硝基苯甲氧基）-2-丙醇lH NMR (CDC13) 8.30 (m? 1H)? 8.22 (d? J = 8.0 Hz? 1H)? 7.77 (d5 J = 8.0 Hz, 1H), 7.61 (m, 1H), 4·76 (s, 2H) , 3.99 (m, 1H), 3.64 (m, 2H), 2.50-2.80 (m, 6H), 1.54 (m, 2H), 1.39 (m, 2H), 1.14 (t, J = 7·0 Hz, 3H ), 1.00 (t, J = 7.0 Hz, 3H)· 1-propenylamino-3-(3-nitrobenzyloxy)-2-propanol

巾 NMR (CDC13) 8.20 (m，1H)，8.15 (d，J = 8.0 Hz，1H)，7·67 (d， J = 8·0 Hz，1H)，7.53 (m，1H)，5.90 (m5 1H)，5·20 (m，2H)，4.66 (s， 2H)，4.00，4.25 (each m，1H)，3.56 (m，2H)，3.35 (m，2H)， 2.60-2.85 (m5 2H). 1-(丁基甲胺基）-3-(3-硝基苯甲氧基）-2-丙醇Towel NMR (CDC13) 8.20 (m, 1H), 8.15 (d, J = 8.0 Hz, 1H), 7·67 (d, J = 8·0 Hz, 1H), 7.53 (m, 1H), 5.90 (m5) 1H), 5·20 (m, 2H), 4.66 (s, 2H), 4.00, 4.25 (each m, 1H), 3.56 (m, 2H), 3.35 (m, 2H), 2.60-2.85 (m5 2H) 1-(butylmethylamino)-3-(3-nitrobenzyloxy)-2-propanol

lU NMR (CDCI3) 8.25 (m? 1H)5 8.22 (d? J = 8.0 Hz? 1H)? 7.68 (d? J =8·0 Hz，1H)，7.53 (m，1H)，4.68 (s，2H)，4.00 (m，lH)，3.55 (m， 0296-A20652TWF(N2)；323；Uofung 37 1294414 2H)，2.59 (m，2H)，2.49 (m，2H)， 2.37 (s，3H)，0·92 (t，J = 7.0 Hz，3H). 1-(2-二甲胺乙胺基）-3-(苯硫基-3-甲氧基）-2-丙醇lU NMR (CDCI3) 8.25 (m? 1H)5 8.22 (d? J = 8.0 Hz? 1H)? 7.68 (d? J =8·0 Hz, 1H), 7.53 (m, 1H), 4.68 (s, 2H) ), 4.00 (m, lH), 3.55 (m, 0296-A20652TWF (N2); 323; Uofung 37 1294414 2H), 2.59 (m, 2H), 2.49 (m, 2H), 2.37 (s, 3H), 0 · 92 (t, J = 7.0 Hz, 3H). 1-(2-Dimethylaminoethylamino)-3-(phenylthio-3-methoxy)-2-propanol

4 NMR (CDC13) 7.16 (m，1H)，7.09 (s，1H)，6·92 (m，1H)，4.40 (s，2Η)，4.00 (m，1Η)，3.40 (m，1Η)，3·36 (m，1Η)，2.75-3.00 (m， 5H)，2·50 (m，1H)，2.29 (s，6H)· 1·(第二丁胺基）-3-(苯硫基-3-甲氣基）-2-丙醇4 NMR (CDC13) 7.16 (m,1H), 7.09 (s,1H),6·92 (m,1H), 4.40 (s,2Η), 4.00 (m,1Η), 3.40 (m,1Η),3 · 36 (m, 1 Η), 2.75-3.00 (m, 5H), 2·50 (m, 1H), 2.29 (s, 6H) · 1 · (second butylamino)-3-(phenylthio- 3-methyl-based)-2-propanol

咕 NMR (CDC13) 7.29 (m，1H)，7.21 (s，1H)，7·05 (m，1H)，4.53 (s，2H)，4·16 (m，1H)，3.40-3.50 (m，2H)，3.36 (m，1H)，2.75-3.00 (m，3H)，1.75 (m，1H)，1.50 (m，1H)，1.25 (t，J = 7.0 Hz，3H)， 0.93 (t，J = 7.0 Hz，3H)· 1_辛胺基·3-(苯硫基-3-甲氧基）-2-丙醇咕NMR (CDC13) 7.29 (m,1H), 7.21 (s,1H),7·05 (m,1H),4.53 (s,2H),4·16 (m,1H), 3.40-3.50 (m, 2H), 3.36 (m, 1H), 2.75-3.00 (m, 3H), 1.75 (m, 1H), 1.50 (m, 1H), 1.25 (t, J = 7.0 Hz, 3H), 0.93 (t, J = 7.0 Hz,3H)·1_octylamino·3-(phenylthio-3-methoxy)-2-propanol

NMR (CDC13) 7.28 (m，1H)，7.20 (s，1H)，7.04 (m，1H)，4.51 (s，2H)，4·16 (m，1H)，3.45, 3.53 (each m，2H)，3·06 (m，2H)， 2.85-2.90 (m，2H)，1.66 (m，2H)，1.25 (m，10H)· 0296-A20652TWF(N2)；323；Uofung 38 1294414 1_二異丙胺基-3-(苯硫基-3-甲氧基）_2_丙醇NMR (CDC13) 7.28 (m, 1H), 7.20 (s, 1H), 7.04 (m, 1H), 4.51 (s, 2H), 4·16 (m, 1H), 3.45, 3.53 (each m, 2H) ,3·06 (m,2H), 2.85-2.90 (m,2H),1.66 (m,2H),1.25 (m,10H)· 0296-A20652TWF(N2);323;Uofung 38 1294414 1_diisopropylamine 3-(phenylthio-3-methoxy)-2-propanol

lR NMR (CDCI3) 7.30 (m? 1H)5 7.18 (s? 1H)? 7.03 (m? 1H)? 4.54 (s，2H)，4.25 (m，1H)，3·63 (m, 1H)，3.53 (m，2H)，3·38 (m，1H)， 3.10 (m，1H)，2.83 (m，1H)，1.25-1.36 (m，12H). 1-己胺基-3-(苯硫基-3-甲氧基）-2-丙醇lR NMR (CDCI3) 7.30 (m? 1H)5 7.18 (s? 1H)? 7.03 (m? 1H)? 4.54 (s, 2H), 4.25 (m, 1H), 3·63 (m, 1H), 3.53 (m, 2H), 3·38 (m, 1H), 3.10 (m, 1H), 2.83 (m, 1H), 1.25-1.36 (m, 12H). 1-hexylamino-3-(phenylthio) -3-methoxy)-2-propanol

巾 NMR (CDC13) 7.30 (m，1H)，7.21 (s，1H)，7_04 (m，1H)，4·53 (s，2H)，4.13 (m，1H)，3.54 (m，1H)，3·46 (m，1H)，2.82-3.02 (m， 4H)，1.66 (m, 2H)，1.20-1.35 (m，6H)，0.88 (t，J = 7.0 Hz，3H)· 1-丁胺基-3-(苯硫基_3-甲氧基）-2-丙醇Towel NMR (CDC13) 7.30 (m, 1H), 7.21 (s, 1H), 7_04 (m, 1H), 4·53 (s, 2H), 4.13 (m, 1H), 3.54 (m, 1H), 3 · 46 (m, 1H), 2.82-3.02 (m, 4H), 1.66 (m, 2H), 1.20-1.35 (m, 6H), 0.88 (t, J = 7.0 Hz, 3H)· 1-butylamino -3-(phenylthio-3-methoxy)-2-propanol

4 NMR (CDC13) 7.30 (m，1H)，7.21 (s，1H)，7.04 (m，1H)，4.53 (s，2H)，4.13 (m，1H)，3.54 (m，1H)，3.46 (m，1H)，2·82-3·02 (m， 4H)，1.66 (m，2H)，1.35 (m，2H)，0.92 (t5 J = 7.0 Hz，3H)· 1-苯胺基-3-(苯硫基-3-甲氧基）-2-丙醇 0296-A20652TWF(N2)；323；Uofung 39 1294414 4 NMR (CDC13) 7.20 (m，3H)，7·10 (m，4H)，6·95 (m，1Η)，4·40 (s，2H)，4.13 (m，1H)，3·43 (m5 1H)，3.35 (m，lH)，2.77-2.91 (m， 4H)，2·57 (t，J = 7.5 Hz，2H)，1.92 (t，J = 7·5 Hz，2H). 1-(3-苯基丙胺基）-3-(苯硫基-3-甲氧基）-2-丙醇 C6H5，h !H NMR (CDCls) 7.28 (m5 3H), 7.18 (m? 4H)? 7.03 (m? 1H)? 4.49 (s，2H)，4.13 (m，1H)，3.52 (m，1H)，3.43 (m，1H)，2.75-3.05 (m， 4H)，2.65 (t，J = 7.5 Hz，2H)，2·02 (m，2H)· 1 - (丁基甲胺基）-3-(苯硫基-3-甲氧基）-2 -丙醇4 NMR (CDC13) 7.30 (m, 1H), 7.21 (s, 1H), 7.04 (m, 1H), 4.53 (s, 2H), 4.13 (m, 1H), 3.54 (m, 1H), 3.46 (m) ,1H),2·82-3·02 (m, 4H), 1.66 (m, 2H), 1.35 (m, 2H), 0.92 (t5 J = 7.0 Hz, 3H)· 1-anilino-3-() Phenylthio-3-methoxy)-2-propanol 0296-A20652TWF(N2); 323; Uofung 39 1294414 4 NMR (CDC13) 7.20 (m, 3H), 7·10 (m, 4H), 6· 95 (m,1Η),4·40 (s,2H), 4.13 (m,1H),3·43 (m5 1H),3.35 (m,lH),2.77-2.91 (m, 4H),2·57 (t, J = 7.5 Hz, 2H), 1.92 (t, J = 7.5 Hz, 2H). 1-(3-phenylpropylamino)-3-(phenylthio-3-methoxy)- 2-propanol C6H5, h !H NMR (CDCls) 7.28 (m5 3H), 7.18 (m? 4H)? 7.03 (m? 1H)? 4.49 (s, 2H), 4.13 (m, 1H), 3.52 (m , 1H), 3.43 (m, 1H), 2.75-3.05 (m, 4H), 2.65 (t, J = 7.5 Hz, 2H), 2·02 (m, 2H)· 1 - (butylmethylamino)-3 -(phenylthio-3-methoxy)-2-propanol

咕 NMR (CDC13) 7.25 (m，1H)，7·18 (m，1H)，7.03 (m，1H)，4.47 (s，2H)，4.10 (m，1H)，3.52 (m，1H)，3.43 (m，1H)，2.75-3.05 (m， 4H)，2.60 (s，3H)，1.50 (m, 2H)，1.25 (m，2H)，0.88 (t，J = 7.5 Hz， 3H). 1-苯甲氧基-3-二丁胺基·2 -丙醇 η_Βυ、Μ，Υ^Ο 八 e6H5咕NMR (CDC13) 7.25 (m,1H),7·18 (m,1H), 7.03 (m,1H), 4.47 (s,2H),4.10 (m,1H),3.52 (m,1H),3.43 (m, 1H), 2.75-3.05 (m, 4H), 2.60 (s, 3H), 1.50 (m, 2H), 1.25 (m, 2H), 0.88 (t, J = 7.5 Hz, 3H). Benzyloxy-3-dibutylamino-2-propanol η_Βυ, Μ, Υ^Ο eight e6H5

ή-BuOH 4 NMR (CDC13) 7.25 (m，1H)，4·50 (s，2H)，3·84 (m，1H)，3·45 (m，2H)，2.30-2.60 (m，6H)，1.30 (m, 4H)，1.25 (m，4H)，0·85 (t，J =7·5 Hz，6H). 0296-A20652TWF(N2)；323；Uofung 40 1294414 、 1-苯甲氧基-3-(丁基乙胺基）-2•丙醇 Β、Ν八丫〜0八糾5ή-BuOH 4 NMR (CDC13) 7.25 (m,1H),4·50 (s,2H),3·84 (m,1H),3·45 (m,2H), 2.30-2.60 (m,6H) , 1.30 (m, 4H), 1.25 (m, 4H), 0·85 (t, J = 7. 5 Hz, 6H). 0296-A20652TWF (N2); 323; Uofung 40 1294414, 1-benzyloxy -3-(butylethylamino)-2•propanol oxime, Ν八丫~0八纠5

n-Bu OH ]H NMR (CDCI3) 7.25 (m5 1H)? 4.50 (s? 2H)5 3.75 (m? 1H)5 3.42 (m，2H)，2.30義2.60 (m5 6H)，1.35 (m，2H)，1.23 (m，2H)，0.96 (t，J =7.0 Hz，3H)，0.84 (t，J = 7·0 Hz，3H)· 1-二丁胺基-3-(苯硫基-3-甲氧基）-2-丙醇n-Bu OH ]H NMR (CDCI3) 7.25 (m5 1H)? 4.50 (s? 2H)5 3.75 (m? 1H)5 3.42 (m,2H), 2.30=2.60 (m5 6H), 1.35 (m, 2H) ), 1.23 (m, 2H), 0.96 (t, J = 7.0 Hz, 3H), 0.84 (t, J = 7·0 Hz, 3H)· 1-dibutylamino-3-(phenylthio-3) -methoxy)-2-propanol

!H NMR (CDCI3) 7.22 (m? 1H)? 7.19 (m? 1H)5 7.02 (m?lH)5 4.51 (s5 2H)? 3.75 (m? 1H)5 3.42 (m? 2H)? 2.25 -2.50 (m, 6H)? 1.35 (m? 4H)，1.23 (m，4H)，，0.84 (t，J = 7_0 Hz，6H). 1-丙烯胺基-3-(苯硫基-3-甲氧基）-2-丙醇 4 NMR (CDC13) 7·22 (m，1H)，7.14 (m，1H)，6.99 (m，lH)，5.75 (m，1H)，5.14 (m，2H)，4.51 (s，2H)，3.75 (m，1H), 3.40 (m，2H)， 2.50 (m? 2H). 1-(丁基乙胺基）-3-(苯硫基-3-甲氧基）_2-丙醇 4 NMR (CDC13) 7.22 (m，1H)，7·15 (m，1H)，7.00 (m，lH)，4.51 (s，2H)，3.73 (m，1H), 3.40 (m，2H)，2.25-2.50 (m，6H)，1.34 (m， 0296-A20652TWF(N2)；323；Uofung 41 1294414 2H), 1.22 (m, 2H), 0.93 (t, 7.5 Hz, 3H), 0.83 (t, J = 7.5 Hz, 3H). 3-(2-二甲胺乙胺基）-l·甲氧基-1-苯基-2 -丙醇 I c6h5 八γ^Ό〇Η3!H NMR (CDCI3) 7.22 (m? 1H)? 7.19 (m? 1H)5 7.02 (m?lH)5 4.51 (s5 2H)? 3.75 (m? 1H)5 3.42 (m? 2H)? 2.25 -2.50 (m, 6H)? 1.35 (m? 4H), 1.23 (m, 4H),, 0.84 (t, J = 7_0 Hz, 6H). 1-Acrylamino-3-(phenylthio-3-methoxy ))-2-propanol 4 NMR (CDC13) 7·22 (m, 1H), 7.14 (m, 1H), 6.99 (m, lH), 5.75 (m, 1H), 5.14 (m, 2H), 4.51 (s, 2H), 3.75 (m, 1H), 3.40 (m, 2H), 2.50 (m? 2H). 1-(butylethylamino)-3-(phenylthio-3-methoxy) _2-propanol 4 NMR (CDC13) 7.22 (m, 1H), 7·15 (m, 1H), 7.00 (m, lH), 4.51 (s, 2H), 3.73 (m, 1H), 3.40 (m, 2H), 2.25-2.50 (m, 6H), 1.34 (m, 0296-A20652TWF (N2); 323; Uofung 41 1294414 2H), 1.22 (m, 2H), 0.93 (t, 7.5 Hz, 3H), 0.83 ( t, J = 7.5 Hz, 3H). 3-(2-Dimethylaminoethylamino)-l-methoxy-1-phenyl-2-propanol I c6h5 八γ^Ό〇Η3

H OH 巾 NMR (CDC13) 735 (m，5H)，4.30, 4.25 (each m，1H)，4.00 (m，lH)，3.26, 3.31 (each s，3H)，2.50-2.80 (m，4H)，2.33 (m，5H)， 1.99 (s，3H)· 3_二丁胺基-1·甲氧基-1-苯基-2-丙醇H OH towel NMR (CDC13) 735 (m, 5H), 4.30, 4.25 (each m, 1H), 4.00 (m, lH), 3.26, 3.31 (each s, 3H), 2.50-2.80 (m, 4H), 2.33 (m,5H), 1.99 (s,3H)· 3_dibutylamino-1·methoxy-1-phenyl-2-propanol

!H NMR (CDC13) 7.35 (m，1H)，4·16 (m，1H)，4·05 (m，1H)，3.78 (m，1H)，2.70，2.60 (each m，2H)，2.50，2.40 (each m，4H)， 1·25-1·50 (m，8H)，0.92 (t5 J = 7.0 Hz，6H)· 3-(苯基甲胺基）-1-甲氧基-1-苯基-2-丙醇 c6h5!H NMR (CDC13) 7.35 (m, 1H), 4·16 (m, 1H), 4·05 (m, 1H), 3.78 (m, 1H), 2.70, 2.60 (each m, 2H), 2.50, 2.40 (each m,4H), 1·25-1·50 (m,8H),0.92 (t5 J = 7.0 Hz,6H)· 3-(phenylmethylamino)-1-methoxy-1- Phenyl-2-propanol c6h5

CeHs^N^Y^OCHs CH3 OH 4 NMR (CDC13) 7.35 (m，10H)，4.19, 4.13, 3.99 (each m，2H)， 3.83, 3.59, 3.53, 3.47, 3.36 (each m，2H)，2.65, 2.50, 2.45 (each m，2H)，2.14, 2.09 (each s，3H)· 0296-A20652TWF(N2)；323；Uofung 42 1294414 3-二異丙胺基-1-甲氧基-1-苯基-2-丙醇CeHs^N^Y^OCHs CH3 OH 4 NMR (CDC13) 7.35 (m,10H), 4.19, 4.13, 3.99 (each m,2H), 3.83, 3.59, 3.53, 3.47, 3.36 (each m,2H),2.65 , 2.50, 2.45 (each m, 2H), 2.14, 2.09 (each s, 3H)· 0296-A20652TWF(N2); 323; Uofung 42 1294414 3-diisopropylamino-1-methoxy-1-phenyl 2-propanol

NMR (CDCI3) 7.35 (m? 5H)? 4.14? 3.75 (each m? 2H)? 3.10 (m? 1H)，2.62, 2.82 (each m，2H)，1.04 (m，12H)· 3-(丁基乙胺基）-l·甲氧基-1-苯基-2 -丙醇宁6H5NMR (CDCI3) 7.35 (m? 5H)? 4.14? 3.75 (each m? 2H)? 3.10 (m? 1H), 2.62, 2.82 (each m, 2H), 1.04 (m, 12H)· 3-(butyl Ethylamino)-l-methoxy-1-phenyl-2-propanol 6H5

/1 OH lU NMR (CDCI3) 7.35 (m? 5H)5 4.155 4.03 (each m? 2H)? 3.76 (m5 1H)，3.26 (s，3H)，2.50-2.75 (m，6H)，1.25-1.80 (m，4H)，0.99, 0.94，0.87 n(each t，J = 7.0 Hz, 6H)· 3-苯甲胺基-1-甲氧基-1-苯基-2-丙醇〒6H5/1 OH lU NMR (CDCI3) 7.35 (m? 5H)5 4.155 4.03 (each m? 2H)? 3.76 (m5 1H), 3.26 (s, 3H), 2.50-2.75 (m, 6H), 1.25-1.80 ( m, 4H), 0.99, 0.94, 0.87 n (each t, J = 7.0 Hz, 6H)· 3-benzylamino-1-methoxy-1-phenyl-2-propanol oxime 6H5

CeHs^N^Y^OCHs H OH ]H NMR (CDCI3) 7.30 (m5 5H)? 4.13 (d? J = 7.5 Hz? 1H)? 3.86, 3.76, 3.63 (each m，3H)，3.23 (s，3H)，3.14-3.20 (m，H)，2.51 (m， 2H). 1-甲氧基-3-苯乙胺基-1-苯基-2-丙醇 0296-A20652TWF(N2)；323；Uofung 43 1294414CeHs^N^Y^OCHs H OH ]H NMR (CDCI3) 7.30 (m5 5H)? 4.13 (d? J = 7.5 Hz? 1H)? 3.86, 3.76, 3.63 (each m,3H),3.23 (s,3H ), 3.14-3.20 (m, H), 2.51 (m, 2H). 1-methoxy-3-phenylethylamino-1-phenyl-2-propanol 0296-A20652TWF (N2); 323; Uofung 43 1294414

4 NMR (CDC13) 7·30 (m，10H)，4.22 (m，1H)，3.70-3·85 (m，3H)， 3·25 (s，3H)，3·75 (m，4H)· 3-(丁基甲胺基）-1-甲氧基-1-苯基_2 -丙醇 c6h5 ch3 oh lU NMR (CDCls) 7.30 (m? 5H)? 4.18, 4.03 (each 1H)? 3.81 (m9 i 1H)，3.27 (s，3Ή)，2.20-2.60 (m，6H)，1.97 (m，1H)，1.37 (m，2H)， 1.28 (m，2H)，0·89 (t，J = 7·0 Hz，3H). 3-己胺基-1-甲氧基-1-苯基-2-丙醇 c6h54 NMR (CDC13) 7·30 (m, 10H), 4.22 (m, 1H), 3.70-3·85 (m, 3H), 3·25 (s, 3H), 3·75 (m, 4H)· 3-(butylmethylamino)-1-methoxy-1-phenyl-2-propanol c6h5 ch3 oh lU NMR (CDCls) 7.30 (m? 5H)? 4.18, 4.03 (each 1H)? 3.81 (m9 i 1H), 3.27 (s, 3Ή), 2.20-2.60 (m, 6H), 1.97 (m, 1H), 1.37 (m, 2H), 1.28 (m, 2H), 0·89 (t, J = 7· 0 Hz, 3H). 3-hexylamino-1-methoxy-1-phenyl-2-propanol c6h5

Η OH 4 NMR (CDC13) 7.30 (m，5Η)，4.08, 3.90(each m，1Η)，3·25 (s， 3H)，2.45-2.52 (m，4H)，1.42 (m，2H)，1.27 (m，6H)，0·87 (t，J = 7·0 Hz，3H)· 3-丙烯胺基-1-甲氧基-1_苯基-2-丙醇 c6h5 N 八'y^OCHsΗ OH 4 NMR (CDC13) 7.30 (m, 5 Η), 4.08, 3.90 (each m, 1 Η), 3·25 (s, 3H), 2.45-2.52 (m, 4H), 1.42 (m, 2H), 1.27 (m,6H),0·87 (t,J = 7·0 Hz,3H)· 3-propenylamino-1-methoxy-1_phenyl-2-propanol c6h5 N 八'y^OCHs

H OH !H NMR (CDC13) 7.30 (m，5H)，5.89 (m，1H)，5·13 (m，2H)，4.23 0296-A20652TWF(N2)；323；Uofung 44 1294414 (m, 1H), 3.81 (m, 1H), 3.28 (s, 3H), 3.21 (m, 2H), 2.75, 2.68 (each 2H). 3-丁胺基-1-甲氣基-1-苯基-2-丙醇H OH !H NMR (CDC13) 7.30 (m, 5H), 5.89 (m, 1H), 5·13 (m, 2H), 4.23 0296-A20652TWF (N2); 323; Uofung 44 1294414 (m, 1H), 3.81 (m, 1H), 3.28 (s, 3H), 3.21 (m, 2H), 2.75, 2.68 (each 2H). 3-butylamino-1-methoxyl-1-phenyl-2-propanol

f6H5 H〇H lU NMR (CDCls) 7.30 (m? 5H), 4.20 (m? 1H)? 3.79 (m? 1H)? 3.27 (s，3H)，2.71 (m，1H)，2.64 (m，1H)，2.54 (m，2H)，1.42 (m，2H)， 1.30 (m，3H)，0.89 (t，J = 7·5 Hz，3H)· 3-[2_(2-氟苯胺基）乙胺基】-l-甲氧基-1-苯基-2-丙醇f6H5 H〇H lU NMR (CDCls) 7.30 (m? 5H), 4.20 (m? 1H)? 3.79 (m? 1H)? 3.27 (s,3H), 2.71 (m,1H), 2.64 (m,1H) , 2.54 (m, 2H), 1.42 (m, 2H), 1.30 (m, 3H), 0.89 (t, J = 7·5 Hz, 3H)· 3-[2_(2-fluoroanilino)ethylamine 】-l-methoxy-1-phenyl-2-propanol

4 NMR (CDC13) 7·30 (m, 5H)，7.17, 7.04 (each m，4H)，4.20 (m， 1H)，3.79 (m，1H)，3.25 (s，3H)，2.70-2.90 (m，6H)，2.20 (m，2H). 1-甲氧基-1-苯基-3-(3-苯基丙胺基）-2-丙醇 c6h5 c6h5^^n^Y"〇ch34 NMR (CDC13) 7·30 (m, 5H), 7.17, 7.04 (each m, 4H), 4.20 (m, 1H), 3.79 (m, 1H), 3.25 (s, 3H), 2.70-2.90 (m ,6H),2.20 (m,2H). 1-methoxy-1-phenyl-3-(3-phenylpropylamino)-2-propanol c6h5 c6h5^^n^Y"〇ch3

H OH iH NMR (CDC13) 7.30 (m，10Η)，7·17, 7.04 (each m，4H)，4.20 (m， 0296-A20652TWF(N2)；323；Uofung 45 1294414 1H)，3.79 (m，1H)，3.24 (s，3H)，2·60 (m，2H)，2·50 (m，2H)，2·43 (m，2H)，1.74 (m，2H)· 3-苯甲氧基_1-[2(1丑-吲哚）-3-乙胺基]-2-丁醇H OH iH NMR (CDC13) 7.30 (m, 10 Η), 7.17, 7.04 (each m, 4H), 4.20 (m, 0296-A20652TWF (N2); 323; Uofung 45 1294414 1H), 3.79 (m, 1H) ), 3.24 (s, 3H), 2·60 (m, 2H), 2·50 (m, 2H), 2·43 (m, 2H), 1.74 (m, 2H)· 3-benzyloxy_ 1-[2(1 ugly-吲哚)-3-ethylamino]-2-butanol

lR NMR (CDC13) 8.17 (d? J = 10.0 Hz? 1H)5 7.60 (m5lH)? 7.30 (m，6H)，7.17 (m，1H)，7.10 (m，1H)，6.95 (m，1H)，4.60, 4.43 (each m，2H)，3.60, 3.48 (each m，2H)，2.95 (m5 4H)" 10H)，7.17, 7.04 (each m，4H)，4.20 (m，1H)，3.79 (m, 1H)，3.24 (s，3H)，2.90 (m，4H)，2.73 (m，2H)，1.19 (t，J = 7.0 Hz，3H)· 3-苯甲氧基-1-二異丙胺基-2·丁醇lR NMR (CDC13) 8.17 (d? J = 10.0 Hz? 1H)5 7.60 (m5lH)? 7.30 (m,6H), 7.17 (m,1H), 7.10 (m,1H), 6.95 (m,1H), 4.60, 4.43 (each m, 2H), 3.60, 3.48 (each m, 2H), 2.95 (m5 4H) " 10H), 7.17, 7.04 (each m, 4H), 4.20 (m, 1H), 3.79 (m , 1H), 3.24 (s, 3H), 2.90 (m, 4H), 2.73 (m, 2H), 1.19 (t, J = 7.0 Hz, 3H)· 3-Benzyloxy-1-diisopropylamino -2·butanol

lH NMR (CDCI3) 7.33 (m, 5H), 4.66, 4.57 (each m9 2H)? 3.48 (m? 1H)，3.03 (m，1H)，2.75 (m，1H)，2.46 (m，1H)，2.36 (m，1H)， 1·28，1·23 (each m，3H)，0.98-1.06 (m，12H)· 3-苯甲氧基-1-環己胺基-2-丁醇巾 NMR (CDC13) 7·26 (m，5H)，4.57, 4·41 (each m，2H)，3.53, 3·44 (each m，2H)，2.73, 2.56 (each m，2H)，2.30 (m，lH)，1.78, 1.64 (each m，4H)，1.50 (m5 1H)，1.15 (m，6H)，0.96 (m，2H). 0296-A20652TWF(N2)；323；Uofung 46 1294414 3-苯甲氧基-1-(2-二甲基乙胺基）-2-丁醇lH NMR (CDCI3) 7.33 (m, 5H), 4.66, 4.57 (each m9 2H)? 3.48 (m? 1H), 3.03 (m, 1H), 2.75 (m, 1H), 2.46 (m, 1H), 2.36 (m,1H), 1·28,1·23 (each m,3H),0.98-1.06 (m,12H)· 3-Benzyloxy-1-cyclohexylamino-2-butanol towel NMR ( CDC13) 7·26 (m,5H),4.57, 4·41 (each m,2H),3.53, 3·44 (each m,2H),2.73, 2.56 (each m,2H),2.30 (m,lH ), 1.78, 1.64 (each m, 4H), 1.50 (m5 1H), 1.15 (m, 6H), 0.96 (m, 2H). 0296-A20652TWF (N2); 323; Uofung 46 1294414 3-benzyloxy -1-(2-dimethylethylamino)-2-butanol

·〇八c6h5 4 NMR (CDC13) 7·27 (m，5H)，4.56, 4.44 (each m，2H)，3.58 (m，2H)，2.73, 2.56 (each m，4H)，2.22 (s，6H)，1.15 (m，3H). 3-苯甲氧基-1-(丁基甲胺基）-2•丁醇·〇八c6h5 4 NMR (CDC13) 7·27 (m,5H),4.56, 4.44 (each m,2H),3.58 (m,2H),2.73, 2.56 (each m,4H),2.22 (s,6H ), 1.15 (m, 3H). 3-Benzyloxy-1-(butylmethylamino)-2•butanol

0 八 c6h5 ch3 oh lR NMR (CDC13) 7.27 (m? 5H)? 4.57, 4.46 (each m5 2H)5 3.56 (m? 1H)，3.43 (m，1H)，2.40-2.60 (m, 4H)，2.17 (s，3H)，1.36，1.24 (each m，4H)，1.23 (m，3H)，0.84 (t，J = 7·5 Hz，3H)· 3-苯甲氧基-1-(甲基苯胺基）_2-丁醇 CH3 C6H5^^Y^〇^C6H5 ch3 oh 巾 NMR (CDC13) 7.27 (m，5H)，7·16 (m，2H)，6.72 (m, 3H)，4.60, 4.40 (each m，2H)，3·88,3·75 (each m，1H)，3.52，3.42，3.23 (each m，2H)，2.88, 2.86 (each s，3H)，1.23 (d，J = 7.2 Hz，3H)· 3-苯甲氧基-1-異丙胺基-2-丁醇 ch3 ch30 八 c6h5 ch3 oh lR NMR (CDC13) 7.27 (m? 5H)? 4.57, 4.46 (each m5 2H)5 3.56 (m? 1H), 3.43 (m, 1H), 2.40-2.60 (m, 4H), 2.17 (s,3H), 1.36, 1.24 (each m, 4H), 1.23 (m, 3H), 0.84 (t, J = 7·5 Hz, 3H)· 3-Benzyloxy-1-(methylaniline) )-butanol CH3 C6H5^^Y^〇^C6H5 ch3 oh towel NMR (CDC13) 7.27 (m,5H),7·16 (m,2H),6.72 (m, 3H), 4.60, 4.40 (each m,2H),3·88,3·75 (each m,1H),3.52,3.42,3.23 (each m,2H),2.88, 2.86 (each s,3H),1.23 (d,J = 7.2 Hz, 3H)· 3-Benzyloxy-1-isopropylamino-2-butanol ch3 ch3

0296-A20652TWF(N2)；323；Uofung 47 1294414 4 NMR (CDC13) 7·27 (m，5H)，4.57, 4.40 (each m，2H)，3.55, 3.45 (each m，2H)，2.70 (m，2H)，2.54 (m，lH)，1.15 (m，3H)，0.97 (m，6H)· 3-苯甲氧基-1-(丁基乙胺基）-2-丁醇0296-A20652TWF(N2); 323; Uofung 47 1294414 4 NMR (CDC13) 7·27 (m, 5H), 4.57, 4.40 (each m, 2H), 3.55, 3.45 (each m, 2H), 2.70 (m, 2H), 2.54 (m, lH), 1.15 (m, 3H), 0.97 (m, 6H)· 3-benzyloxy-1-(butylethylamino)-2-butanol

!H NMR (CDCIs) 7.27 (m? 5H)5 4.58, 4.47 (each m? 2H)? 3.485 3.42 (each m5 2H)? 2.54 (m5 2H)? 2.42 (m? 2H)? 2.32 (m? 2H)? 1.33 (m，2H)，1.20 (m，1H)，1.18 (d，J = 6·2 Hz，3H)，1.10 (m，1H)， 0.93 (t5 J = 7.0 Hz，3H)，0.83 (t，J = 7·0 Hz，3H). 3-苯甲氧基-1-第二丁胺基-2-丁醇!H NMR (CDCIs) 7.27 (m? 5H)5 4.58, 4.47 (each m? 2H)? 3.485 3.42 (each m5 2H)? 2.54 (m5 2H)? 2.42 (m? 2H)? 2.32 (m? 2H) ? 1.33 (m, 2H), 1.20 (m, 1H), 1.18 (d, J = 6·2 Hz, 3H), 1.10 (m, 1H), 0.93 (t5 J = 7.0 Hz, 3H), 0.83 (t , J = 7·0 Hz, 3H). 3-Benzyloxy-1-second butyryl-2-butanol

4 NMR (CDC13) 7.27 (m, 5H)，4.58, 4.40 (each m，2H)，3.48, 3.45 (each m5 2H)，2.70, 2.45 (each m，3H)，1.40, 1.25 (each m， 2H)，1.14 (m，3H)，0.94 (m，3H)，0.80 (m，3H). 3-苯甲氧基-1-苯胺基-2-丁醇 ch3 06Η5ΝΗχ^γ^Ο^〇6Η54 NMR (CDC13) 7.27 (m, 5H), 4.58, 4.40 (each m, 2H), 3.48, 3.45 (each m5 2H), 2.70, 2.45 (each m, 3H), 1.40, 1.25 (each m, 2H) , 1.14 (m, 3H), 0.94 (m, 3H), 0.80 (m, 3H). 3-Benzyloxy-1-anilino-2-butanol ch3 06Η5ΝΗχ^γ^Ο^〇6Η5

OH 4 NMR (CDC13) 7·36 (m5 5Η)，7·17 (m5 2Η)，6·62 (m，3Η), 4.69, 0296-A20652TWF(N2)；323；Uofung 48 1294414 4.47 (each m，2H)，3.71，3.62 (each m，2H)，3.30，3.13 (each m, 2H)，1.27 (m，3H)· 3 -苯甲氧基-1-(2 -乙基苯胺基)-2 -丁醇OH 4 NMR (CDC13) 7·36 (m5 5Η), 7·17 (m5 2Η), 6·62 (m, 3Η), 4.69, 0296-A20652TWF(N2); 323; Uofung 48 1294414 4.47 (each m, 2H), 3.71, 3.62 (each m, 2H), 3.30, 3.13 (each m, 2H), 1.27 (m, 3H)· 3 -benzyloxy-1-(2-ethylanilino)-2 Butanol

h 〇八 c6h5 iH NMR (CDC13) 7.27 (m，5H)，7.22 (d，J = 8.0 Hz，1H)，6.98 (d， J = 7.0 Hz，1H)，6.64 (m，1H)，6.57 (d，J = 8.0 Hz，1H)，4.60 (d，J =11·5 Hz，1H)，4.42 (d，J = 11·5 Hz，1H)，3.80, 3·66 (each m，2H)， 3·33, 3·10 (each m，2H)，2·33 (m，2H)，1.21 (m，3H)，1-10 (m， 3H). 3 -苯甲氧基-1-(乙基苯胺基）-2 -丁醇 ch3h 〇8 c6h5 iH NMR (CDC13) 7.27 (m, 5H), 7.22 (d, J = 8.0 Hz, 1H), 6.98 (d, J = 7.0 Hz, 1H), 6.64 (m, 1H), 6.57 (d , J = 8.0 Hz, 1H), 4.60 (d, J = 11·5 Hz, 1H), 4.42 (d, J = 11·5 Hz, 1H), 3.80, 3·66 (each m, 2H), 3 ·33, 3·10 (each m, 2H), 2·33 (m, 2H), 1.21 (m, 3H), 1-10 (m, 3H). 3-benzyloxy-1-(ethyl) Anilino)-2-butanol ch3

c6h5n"^y^o^c6h5 ;OH NMR (CDC13) 7.47 (m，5H)，7·33 (m，2H)，6·88 (m，1H)，4.79, 4.60 (each m，2H)，4.00，4.85 (each m，1H)，3.72 (m，1H)， 3·30·3·60 (m，4H)，1.41 (t，J = 7.5 Hz，3H)，1.23 (m, 3H)· 1-(苯基甲胺基）-3-苯甲氧基-2-丁醇 ch3 c6h5^n"^Y^o^c6h5 ch3 oh lU NMR (CDC13) 7.17-7.25 (m5 10H)? 4.54 (d? J = 11.8 Hz? 1H)? 4.42 (d，J = 11.8 Hz，1H)，3.63 (m，2H)，3.42 (m, 2H)，2·48 0296-A20652TWF(N2)；323；Uofung 49 1294414 (m，2H)，2.15 (s，3H)，1.13 (m，3H)· 3-苯甲氧基-1-環己胺基-2-己醇C6h5n"^y^o^c6h5;OH NMR (CDC13) 7.47 (m,5H),7·33 (m,2H),6·88 (m,1H), 4.79, 4.60 (each m,2H), 4.00 , 4.85 (each m, 1H), 3.72 (m, 1H), 3·30·3·60 (m, 4H), 1.41 (t, J = 7.5 Hz, 3H), 1.23 (m, 3H)· 1- (Phenylmethylamino)-3-benzyloxy-2-butanol ch3 c6h5^n"^Y^o^c6h5 ch3 oh lU NMR (CDC13) 7.17-7.25 (m5 10H)? 4.54 (d? J = 11.8 Hz? 1H)? 4.42 (d, J = 11.8 Hz, 1H), 3.63 (m, 2H), 3.42 (m, 2H), 2·48 0296-A20652TWF (N2); 323; Uofung 49 1294414 (m , 2H), 2.15 (s, 3H), 1.13 (m, 3H) · 3-benzyloxy-1-cyclohexylamino-2-hexanol

lR NMR (CDCI3) 7.40 (m5 5H)? 4.73, 4.63 (each 2H)5 3.80 ( m5 1H)，3.55, 3.45 (each m，1H)，1.30-1.80 (m，12H)，1.00 (m，6H)· 1-苯甲胺基-3-苯甲氧基-2-己醇广ch3 c6h 广八 c6h5lR NMR (CDCI3) 7.40 (m5 5H)? 4.73, 4.63 (each 2H)5 3.80 ( m5 1H), 3.55, 3.45 (each m,1H),1.30-1.80 (m,12H),1.00 (m,6H) · 1-Benzylamino-3-benzyloxy-2-hexanol wide ch3 c6h wide eight c6h5

H OH 巾 NMR (CDC13) 7.40 (m，10H)，4.70, 4.60 (each m，2H)，3·87 (m，3H)，2·83 (m，3H)，1.40-1.80 (m，4H)，1.02 (m，3H). 1-丙烯胺基_3_苯甲氧基-2-己醇广ch3H OH towel NMR (CDC13) 7.40 (m, 10H), 4.70, 4.60 (each m, 2H), 3·87 (m, 3H), 2·83 (m, 3H), 1.40-1.80 (m, 4H) , 1.02 (m, 3H). 1-Acrylamine _3_benzyloxy-2-hexanol wide ch3

n 八八 c6h5 H OH lR NMR (CDCI3) 7.27 (m5 10H)? 5.80 (m? 1H)? 5.09 (m? 1H)? 5.00 (m，1H)，3.66 (m，1H)，3.41，3.30 (each m，1H)，3.18 (m，2H)， 2.64 (m? 2H)? 1.40-1.80 (m5 4H)5 0.85 (m? 3H). 3-苯甲氧基-1-丁胺基_2-己醇 0296-A20652TWF(N2)；323；Uofung 50 1294414 广ch3 八 c6h5n 八八八6 c6h5 H OH lR NMR (CDCI3) 7.27 (m5 10H)? 5.80 (m? 1H)? 5.09 (m? 1H)? 5.00 (m,1H), 3.66 (m,1H), 3.41, 3.30 (each m,1H), 3.18 (m,2H), 2.64 (m? 2H)? 1.40-1.80 (m5 4H)5 0.85 (m? 3H). 3-Benzyloxy-1-butylamino 2-hexyl Alcohol 0296-A20652TWF(N2); 323; Uofung 50 1294414 wide ch3 eight c6h5

H OH ^ NMR (CDC13) 7.27 (m，5H)，4.56, 4.45 (each m，2H)，3·63 (m， 1H)，3.40, 3.50 (each m，1H)，2.40-2.70 (m，4H)，1.20-1.70 (m， 8H)，0.83 (m，6H)· 3 -苯甲氧基-1-(3-苯基丙胺基）-2 -己醇广ch3 八 C6H5H OH ^ NMR (CDC13) 7.27 (m, 5H), 4.56, 4.45 (each m, 2H), 3·63 (m, 1H), 3.40, 3.50 (each m, 1H), 2.40-2.70 (m, 4H ), 1.20- 1.70 (m, 8H), 0.83 (m, 6H) · 3-benzyloxy-1-(3-phenylpropylamino)-2-hexanol, wide ch3, eight C6H5

H OH !H NMR (CDC13) 7.26, 7.20, 7·10 (each m，10H)，4.55, 4.45 (each m，2H)，3.63 (m，1H)，3.40, 3·50 (each m，1H)，2.40-2.70 (m，4H)， 1.20-1.70 (m，8H)，0.83 (m,6H)· 3_苯甲氧基-l-[2-(2-氟苯基）-乙胺基】-2-己醇H OH !H NMR (CDC13) 7.26, 7.20, 7·10 (each m,10H), 4.55, 4.45 (each m,2H),3.63 (m,1H), 3.40, 3·50 (each m,1H) , 2.40-2.70 (m, 4H), 1.20-1.70 (m, 8H), 0.83 (m, 6H)· 3_benzyloxy-l-[2-(2-fluorophenyl)-ethylamino] -2-hexanol

lU NMR (CDC13) 7.26, 7.11, 6.95 (each m? 9H)? 4.55, 4.45 (each m，2H)，3.61 (m，1H)，3.40, 3.50 (each m，1H)，2.40-2.70 (m，4H)， 1.20-1.70 (m，4H), 0·85 (t，J = 7.0 Hz，3H)· 1-苯甲氧基-3-(3-二甲胺丙胺基）-2-丙醇八 c6h5 ch3 h oh 0296-A20652TWF(N2)；323；Uofung 51 1294414 . 4 NMR (CDC13) 7.26 (m，5H)，4.49 (s，2H)，3.90, 3.80，3.60 (each m，1H)，1.20-1.0 (m，6H)，2.15, 2.11 (each s，6Η)，2·07 (m， 2H). 1-苯甲胺基-3-苯甲氧基-2-丙醇lU NMR (CDC13) 7.26, 7.11, 6.95 (each m? 9H)? 4.55, 4.45 (each m, 2H), 3.61 (m, 1H), 3.40, 3.50 (each m, 1H), 2.40-2.70 (m, 4H), 1.20-1.70 (m, 4H), 0·85 (t, J = 7.0 Hz, 3H)· 1-Benzyloxy-3-(3-dimethylaminopropylamino)-2-propanol C6h5 ch3 h oh 0296-A20652TWF(N2); 323; Uofung 51 1294414 . 4 NMR (CDC13) 7.26 (m, 5H), 4.49 (s, 2H), 3.90, 3.80, 3.60 (each m, 1H), 1.20- 1.0 (m,6H), 2.15, 2.11 (each s,6Η),2·07 (m, 2H). 1-Benzylamino-3-benzyloxy-2-propanol

巾 NMR (CDC13) 7·26 (m，10H)，4.48 (s，2H)，3·80 (m，1H)，3.70 (m，2Η)，3·42 (m，2Η)，2.68, 2.61 (each m，2Η). 1-苯甲氧基·3·(2-二甲胺乙胺基）-2-丙醇Towel NMR (CDC13) 7·26 (m, 10H), 4.48 (s, 2H), 3·80 (m, 1H), 3.70 (m, 2Η), 3·42 (m, 2Η), 2.68, 2.61 ( Each m,2Η). 1-Benzyloxy·3·(2-dimethylamineethylamino)-2-propanol

4 NMR (CDC13) 7.26 (m，5H)，4.47 (s，2H), 3.80 (m，1H)，3.42 (m，2H)，2·62 (m，4H)，2.30 (m，2H)，2.14 (s，6H). 1-辛胺基-3-(吼啶-2_甲氧基）-2-戊醇4 NMR (CDC13) 7.26 (m, 5H), 4.47 (s, 2H), 3.80 (m, 1H), 3.42 (m, 2H), 2·62 (m, 4H), 2.30 (m, 2H), 2.14 (s,6H). 1-octylamino-3-(acridin-2-yloxy)-2-pentanol

4 NMR (CDC13) 8.56 (m，1H)，7·69 (m，1H)，7.43 (m，1H)，7·20 (m，1H)，4.73 (s，2H)，3.90, 3.75, 3.68, 3.30 (each m，2H)，2.56, 2.65 (each m，4H)，1·25_1·75 (m，14H)，0.96 (t，J = 7.0 Hz，3H)， 0.88 (t，J = 7.0 Hz，3H)· 0296-A20652TWF(N2)；323；Uofung 52 1294414 1-(3-二甲胺丙胺基）-3-(”比啶-2-甲氧基）-2-戊醇4 NMR (CDC13) 8.56 (m,1H),7·69 (m,1H), 7.43 (m,1H),7·20 (m,1H), 4.73 (s,2H), 3.90, 3.75, 3.68, 3.30 (each m, 2H), 2.56, 2.65 (each m, 4H), 1·25_1·75 (m, 14H), 0.96 (t, J = 7.0 Hz, 3H), 0.88 (t, J = 7.0 Hz, 3H)· 0296-A20652TWF(N2); 323; Uofung 52 1294414 1-(3-dimethylamine propylamino)-3-("pyridin-2-methoxy)-2-pentanol

lH NMR (CDCI3) 8.55 (m? 1H)? 7.67 (m? 1H)? 7.32 (m5 1H)? 7.19 (m，1H)，4.84，4.68 (each m，2H)，3.75，3.68，3.38 (each m，2H)， 2·50_2·75 (each m，4H)，2.30 (m，2H)，2·20 (s，6H)，1.40-1.75 (m， 4H)，1.00 (t，J = 7.0 Hz，3H)· 1-苯乙胺基-3-(。比啶-2_甲氧基）·2-戊醇lH NMR (CDCI3) 8.55 (m? 1H)? 7.67 (m? 1H)? 7.32 (m5 1H)? 7.19 (m,1H), 4.84, 4.68 (each m,2H), 3.75, 3.68, 3.38 (each m , 2H), 2·50_2·75 (each m, 4H), 2.30 (m, 2H), 2·20 (s, 6H), 1.40-1.75 (m, 4H), 1.00 (t, J = 7.0 Hz, 3H)· 1-phenylethylamino-3-(.pyridin-2-yloxy)·2-pentanol

巾 NMR (CDC13) 8·47 (m，1Η)，7·60 (m，1Η)，7.30 (m, 1Η)，7·19 (m，2H)，7.13 (m，4H)，4.60 (s，2H)，3.75, 3.60 (each m，2H)， 2.50-2.90 (each m，6H)，1.40-1.75 (m，2H)，0.88 (t，J = 7·0 Hz， 3H). 1-(3-苯基-1-丙胺基）-3-卜比啶-2-甲氧基）_2·戊醇Towel NMR (CDC13) 8·47 (m, 1Η), 7·60 (m, 1Η), 7.30 (m, 1Η), 7·19 (m, 2H), 7.13 (m, 4H), 4.60 (s, 2H), 3.75, 3.60 (each m, 2H), 2.50-2.90 (each m, 6H), 1.40-1.75 (m, 2H), 0.88 (t, J = 7·0 Hz, 3H). 1-(3 -Phenyl-1-propylamino)-3-bupyridin-2-methoxy)_2·pentanol

]H NMR (CDCI3) 8.54 (m? 1H)? 7.68 (m? 1H)? 7.40 (m? 1H)? 7.28 (m，2H)，7.17 (m，4H)，4.68 (s, 2H)，3.75, 3.60, 3.30 (each m，2H)， 0296-A20652TWF(N2)；323；Uofung 53 1294414 2·50_2·75 (each m，6H)，1·40_1·75 (m，4H)，0.92 (t，J = 7.0 Hz， 3H). 1-苯甲胺基_3-(吼啶-2-甲氧基）-2-戊醇]H NMR (CDCI3) 8.54 (m? 1H)? 7.68 (m? 1H)? 7.40 (m? 1H)? 7.28 (m, 2H), 7.17 (m, 4H), 4.68 (s, 2H), 3.75, 3.60, 3.30 (each m, 2H), 0296-A20652TWF(N2); 323; Uofung 53 1294414 2·50_2·75 (each m, 6H), 1·40_1·75 (m, 4H), 0.92 (t, J = 7.0 Hz, 3H). 1-Benzylamino-3-3-(acridin-2-methoxy)-2-pentanol

4 NMR (CDC13) 8·54 (m，1H)，7·66 (m，1H)，7.20-7.40 (m，7H)， 4·68 (s，2H)，3.60-3.90 (each m，4H)，2.60, 2.75 (each m，2H)， 1.50-1.75 (m，2H)，0.93 (t，J = 7.0 Hz，3H)· 1-己胺基-3-(0比咬-2-甲氧基）-2-戍醇4 NMR (CDC13) 8·54 (m, 1H), 7.66 (m, 1H), 7.20-7.40 (m, 7H), 4·68 (s, 2H), 3.60-3.90 (each m, 4H) , 2.60, 2.75 (each m, 2H), 1.50-1.75 (m, 2H), 0.93 (t, J = 7.0 Hz, 3H)· 1-hexylamino-3-(0-bito-2-methoxy -2-nonanol

NMR (CDCls) 8.56 (m? 1H)5 7.70 (m? 1H)? 7.42 (m? 7H)? 7.20 (m，1H)，4.70 (s，2H), 3.65-3.75 (m，2H)，2-50, 2.75 (each 4H)， 1.25-1.75 (m，10H)，0.95 (t，J = 7.0 Hz，3H)，0.90 (t，J = 7.0 Hz， 3H). 【生物活性測定】NMR (CDCls) 8.56 (m? 1H)5 7.70 (m? 1H)? 7.42 (m? 7H)? 7.20 (m,1H), 4.70 (s,2H), 3.65-3.75 (m,2H),2- 50, 2.75 (each 4H), 1.25-1.75 (m, 10H), 0.95 (t, J = 7.0 Hz, 3H), 0.90 (t, J = 7.0 Hz, 3H). [Bioactivity assay]

Fructosamine 3-kinase(FN3K，又稱為 amadorase)抑制物之活性測試 FN3K之酵素活性測試係運用Dynamis所建立的修正過之同位素標定受質測試（ref 1) Brown TR，Su B，Brown KA， 0296-A20652TWF(N2)；323；Uofung 54 1294414Fructosamine 3-kinase (FN3K, also known as amadorase) inhibitor activity The FN3K enzyme activity test was performed using the modified isotope calibration test set by Dynamis (ref 1) Brown TR, Su B, Brown KA, 0296 -A20652TWF(N2);323;Uofung 54 1294414

Schwartz MA? Tobia AM? Kappler Y.Biochem Soc Trans. 2003 Dec;31(Pt 6):1433-7. 2) Kappler F? Schwartz ML, Su B? Tobia AM? BrownT.Diabetes; Technol Ther· 2001 Winter;3(4):609-16.)°¥N3K 蛋白質利用昆蟲的SF-9細胞所表現的N端帶有polyHis的重組蛋白質，而利用鎳的親合管柱加以純化。酵素活性/抑制性的測試是在pH=7.0，37°C的環境下作用10分鐘。反應之混合物包含 37·5ρΜ 之 FN3K(分子量约為 40 kDa)，0.5mM fructolysine， 0.25 mMATP.Mg内含0.2 uCi γ射線標定之磷33 ATP做為標定追蹤劑，以及少於3 mM預先溶於二甲基亞砜的抑制劑。反應物中其他成分包含2-[4_(2-羥乙基）-1-哌嗪]-乙磺酸（HEPES) 50 mM做為酸鹼緩衝劑，二氯化鎂2mM，二硫蘇糖醇（DTT) ImM，小牛血清白蛋白〇.lmg/m卜反應物體積為100ul，最終加入等量的乙二胺四醋酸（EDTA) 25mM以停止反應。反應物中分取85ul 點在一平方呎之P81濾紙。以去離子水清洗五次以洗去其上未反應之ATP受質，並計算生成物3-phosphofructolysine所附的放射線含量(cpm)。此處所列之IC5g表示抑制FN3K酵素活性達 50%時之抑制劑濃度。為達測定IC5C的目的，抑制劑以兩倍序列稀釋以涵蓋IC50的濃度。利用此方法所測出之受測化合物之 IC5〇在mM到μΜ的範圍並具有良好的劑量線性關聯。 0296-A20652TWF(N2)；323；Uofung 55 1294414 【圖式簡單說明】無。【主要元件符號說明】無0 0296-A20652TWF(N2)；323；Uofung 56Schwartz MA? Tobia AM? Kappler Y. Biochem Soc Trans. 2003 Dec; 31(Pt 6): 1433-7. 2) Kappler F? Schwartz ML, Su B? Tobia AM? BrownT.Diabetes; Technol Ther· 2001 Winter; 3(4): 609-16.) The ¥N3K protein was purified using an affinity column of nickel using a recombinant protein of polyHis at the N-terminus expressed by insect SF-9 cells. The enzyme activity/inhibition test was carried out for 10 minutes at pH = 7.0, 37 °C. The reaction mixture contains 37·5ρΜ of FN3K (molecular weight of approximately 40 kDa), 0.5 mM fructolysine, 0.25 mMATP.Mg containing 0.2 uCi of gamma-ray-labeled phosphorus 33 ATP as a calibration tracer, and less than 3 mM pre-dissolved An inhibitor of dimethyl sulfoxide. The other ingredients in the reaction contained 2-[4-(2-hydroxyethyl)-1-piperazine]-ethanesulfonic acid (HEPES) 50 mM as an acid-base buffer, magnesium dichloride 2 mM, dithiothreitol (DTT). ImM, calf serum albumin 〇.lmg/m Bu reactant volume was 100 ul, and finally an equivalent amount of ethylenediaminetetraacetic acid (EDTA) 25 mM was added to stop the reaction. The reaction was divided into 85 ul of P81 filter paper at a square inch. It was washed five times with deionized water to wash off the unreacted ATP substrate thereon, and the emission content (cpm) attached to the product 3-phosphofructolysine was calculated. The IC5g listed here indicates the inhibitor concentration at which the activity of the FN3K enzyme is inhibited by 50%. For the purpose of determining IC5C, the inhibitor was diluted in a two-fold sequence to cover the concentration of IC50. The IC5 of the test compound measured by this method was in the range of mM to μΜ and had a good dose linear correlation. 0296-A20652TWF(N2); 323; Uofung 55 1294414 [Simple description of the diagram] None. [Main component symbol description] No 0 0296-A20652TWF(N2); 323; Uofung 56

Claims

4m 1 54號申5月專利範圍修正本申請專利範圍： 1 · 一種化合物，如式一修正日期：96.1 2.5 (更)正本 OH 0Η4m 1 54 Application May Patent Range Revision The scope of this patent application: 1 · A compound, such as Formula 1 Date of revision: 96.1 2.5 (more) Original OH 0Η

OR1 式一其中 η = 0 ·， 11及Ra分別為1-20個碳原子之烷基或以Cl 8烷基連結之芳香烷基； R為以C〗·4烷基連結之吡啶、以c】_4烷基連結之苯環或以 C“烧基連結經取代之苯環，且…不與其他原子形成環狀結構； Re為Cb4燒基；或一藥學上可接受之鹽類。 2. —種化合物，如式一： OH 0HOR1 Formula 1 wherein η = 0 ·, 11 and Ra are each an alkyl group of 1 to 20 carbon atoms or an aromatic alkyl group bonded by a C 8 alkyl group; R is a pyridine bonded by a C alkyl group, c 】 4 alkyl-bonded benzene ring or C-alkyl group substituted benzene ring, and ... does not form a cyclic structure with other atoms; Re is Cb4 alkyl; or a pharmaceutically acceptable salt. a compound, such as formula 1: OH 0H

式一其中香烧基；力別為1-20個碳原子之烧基或以c“8絲連結之」基’且R、與其他原子形成環狀結構；、\/·4坑基或無醇基取代之c“8烧基；或某學上可接受之鹽類。 57 1294414 3，如申請專利範圍第1或2項所述之化合物，其中該些化合物為： 2- 苯曱氧基-1-十二烷胺基-2-己醇、 3- 苯曱氧基-(3-苯基"丙胺基）-2-己醇、 3 -苯曱氧基-1-十二院胺基-4-曱氧基-2-丁醇、 3-苯曱氧基-4-曱氧基-1-辛胺基-2-丁醇、 3-苯甲氧基-1-十二烷胺基-2-己醇、 3-苯甲氧基-1-十六烷胺基-4-甲氧基-2-丁醇、 3-苯甲氧基-1-十五烷胺基-2-己醇、 3 -苯甲氧基-1-十四烧胺基-2-己醇、 3-苯曱氧基-1-十三烷胺基-2-己醇、 1-十八烧胺基-3-(ϋ比咬-2-甲氧基）-2-己酵、 1-十八烷胺基-3-(吡啶-3-曱氧基）-2-己醇、 1-苯甲氧基-3-十八烧胺基-2-丙醇、 L·苯曱氧基-1-十八烷胺基-2-己醇、 1-辛胺基-3-(吼啶-2-甲氧基）-2-己醇、 1-己胺基-3-(吡啶-2-曱氧基）-2-己醇、 1-丁胺基-3-(咄啶-2-甲氧基）-2-己醇、 3-甲氧基-1-壬胺基-2,4-壬雙醇、 6-(4-氯苯基）-1-己胺基-3-甲氧基-2,4-己雙醇、 6-(4-氯苯基）-3-曱氧基-1-辛胺基-2,4-己雙醇、 6 - (4-氣苯基）-1-葵胺基-3-曱氧基-2,4-己雙醇、 6-(3-氣苯基）-1-(2-二曱胺基乙胺基）-3-甲氧基-2,4-己雙醇、 1-細丙胺基-3 -甲氧基-6-苯基-2,4-己雙醇、 1- (2-二甲胺基乙胺基）-3-甲氧基-6-苯基-2,4-己雙醇、 2- 細丙胺基-6-(3 -氯苯基）-3 -甲氧基-2,4-己雙醇、 58 1294414 1-辛胺基-3-(吼啶-2-甲氧基）-2-戊醇、 H3-二甲胺基丙胺基)-3十比咬么甲氧基)_2_戊醇、 1-苯乙胺基-3-(17比17定-2-曱氧基）、2_戊醇、 1-(3-苯基-1-丙胺基）-3-(吡啶甲氧基）_2_戊醇、 1-苯甲胺基-3十比啶-2-甲氧基）_厶戊醇、 1-己胺基-3-(吡啶_2_甲氧基戊醇。 4 · 一種製備式一之化合物的步驟a scented base; a group of 1-20 carbon atoms or a "8-wire" group and R, and other atoms form a ring structure; / / / 4 pit base or none An alcohol-substituted c"8 alkyl group; or a pharmaceutically acceptable salt. 57 1294414. The compound of claim 1 or 2, wherein the compounds are: 2-benzoquinoneoxy -1-dodecanylamino-2-hexanol, 3-phenylhydroxy-(3-phenyl"propylamino)-2-hexanol, 3-benzophenoxy-1-didoamine 4-methoxy-2-butanol, 3-phenylhydroxy-4-decyloxy-1-octylamino-2-butanol, 3-benzyloxy-1-dodecanamine 2-hexanol, 3-benzyloxy-1-hexadecylamino-4-methoxy-2-butanol, 3-benzyloxy-1-pentadecylamino-2- Hexanol, 3-benzyloxy-1-tetradecylamino-2-hexanol, 3-phenylhydrazino-1-tridecylamino-2-hexanol, 1-octadecylamine -3-(ϋ比 bit-2-methoxy)-2-hexyl, 1-octadecylamino-3-(pyridin-3-yloxy)-2-hexanol, 1-benzyloxy Alkyl-3-octadecylamino-2-propanol, L-benzoyloxy-1-octadecylamino-2-hexanol, 1-octylamine 3-(Acridine-2-methoxy)-2-hexanol, 1-hexylamino-3-(pyridin-2-yloxy)-2-hexanol, 1-butylamino-3 -(Acridine-2-methoxy)-2-hexanol, 3-methoxy-1-indenyl-2,4-indole diol, 6-(4-chlorophenyl)-1-hexyl Amino-3-methoxy-2,4-hexanediol, 6-(4-chlorophenyl)-3-decyloxy-1-octylamino-2,4-hexanediol, 6- ( 4-oxophenyl)-1-ylanamino-3-indolyl-2,4-hexanediol, 6-(3-phenylphenyl)-1-(2-diguanylaminoethyl) 3-methoxy-2,4-hexanediol, 1-fine propylamino-3-methoxy-6-phenyl-2,4-hexanediol, 1-(2-dimethylamino) Amino)-3-methoxy-6-phenyl-2,4-hexanediol, 2-pyridyl-6-(3-chlorophenyl)-3-methoxy-2,4-hexyl Diol, 58 1294414 1-octylamino-3-(acridin-2-methoxy)-2-pentanol, H3-dimethylaminopropylamino)-3 decyl methoxy)_2_ Pentanol, 1-phenylethylamino-3-(17-17-but-2-oxooxy), 2-pentanol, 1-(3-phenyl-1-propylamino)-3-(pyridine methoxy) 2)-2-pentanol, 1-benzylamino-3-decabiidine-2-methoxy)-indolyl alcohol, 1-hexylamino-3-(pyridine-2-methoxyacetol. 4 · A preparation The compound of step

式一其中 R及Rl別分別為1々〇個碳原子之烧基或以烧基連結之芳香烷基； R為以Cl·4烷基連結之吡啶、以C〗_4烷基連結之苯環或以 C】· 4烧基連結姆代之笨環，i R b +與其他原子形成環狀結構； 1^為CN4烷基；或一藥學上可接受之鹽類，包括： a) ,ΝΗ R. Ra’ 乂上式化Π物與下式化合物進行反應，其中R&Ra之定義如上述 0Rb S^RC 59 1294414 其中定義Rb及Rc如上述，具有單一立體異構物並於適當溶劑或無需溶劑的條件下反應；以及 b)選擇性地與藥學用之酸反應以f得藥學上可接受之鹽類 5· 一種製備式一之化合物的步驟 R Ra OH QH ；N-^N^Rc 〇Rb式一其中R及R分別分別為1_2G個碳原子之絲或以c] 8：^基連結之芳香烷基； ^為Cl_4絲，且與其他原子形成環狀結構；Re則為Cw烧基或無醇基取代之Ci_8烷基；或一藥學上可接受之鹽類，包括： a) r%hFormula 1 wherein R and R1 are each a carbon atom or a aryl group bonded to a burnt group; R is a pyridine ring bonded by a C 4 alkyl group, and a benzene ring bonded by a C 4 alkyl group; Or a C 4 · 4 alkyl group is a ring of md, i R b + forms a cyclic structure with other atoms; 1 ^ is a CN 4 alkyl group; or a pharmaceutically acceptable salt, including: a) , ΝΗ R. Ra' 乂式 Π 与与 , , R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R R Reaction without solvent; and b) selectively reacting with a pharmaceutical acid to obtain a pharmaceutically acceptable salt. 5. A step of preparing a compound of formula I R Ra OH QH ; N-^N^Rc 〇Rb is a formula wherein R and R are respectively 1_2G carbon atoms or an alkyl group bonded by c 8:^; ^ is Cl_4 filament and forms a cyclic structure with other atoms; Re is Cw a Ci_8 alkyl group substituted with or without an alcohol group; or a pharmaceutically acceptable salt, including: a) r%h

以上式化合物與下式化合物進行反應，其中R及之定義如上述The compound of the above formula is reacted with a compound of the formula wherein R is as defined above

60 1294414 八中R及R係如上述所定義之化合物，其中具有删氫化納或喊氳化鈉，並於適當溶劑或混合溶劑的條件下反應；以及 b)選擇性i：也與藥學用《酸反應以製得藥學上可接受之鹽類。 .6· 一種製備式一之化合物的步驟 Ra>~^V^〇CH3 0Rb 式一其中 R及R /刀別分別4 1-20個碳原子之烷基或以a -8丈完基連結之芳香烧基； R為以c!.4烧基連結之口比咬、卩烧基連結之苯環或以 C“4院基連U取代之笨環，且Rb^與其他原子形成環狀結構；或一藥學上可接受之鹽類，包括： a) R、 Ra.NH 以上式化合物與下式化合物進行反應，其中尺及Ra之定義如上述 r och3 ORb 61 1294414 其中Rb如上述所定義，而該類環氧化物乃由下述方法合成；以及60 1294414 VIII R and R are compounds as defined above, which have sodium hydride or sodium hydride, and are reacted in a suitable solvent or mixed solvent; and b) selectivity i: also used in pharmaceuticals. The acid is reacted to produce a pharmaceutically acceptable salt. .6· A step of preparing a compound of formula I>>~^V^〇CH3 0Rb Formula 1 wherein R and R/knife are respectively alkyl groups of 4 1-20 carbon atoms or are bonded at a -8 Å Aromatic alkyl; R is a benzene ring linked by a c..4 alkyl group than a bite, a sulphur-burning group or a stupid ring substituted with a C-four-substituent U, and Rb^ forms a cyclic structure with other atoms. Or a pharmaceutically acceptable salt, comprising: a) R, Ra. NH The compound of the above formula is reacted with a compound of the formula wherein the ruler and Ra are as defined above for r och3 ORb 61 1294414 wherein Rb is as defined above, And such epoxides are synthesized by the following methods;

|-〇Η -OH Bn〇- l〇h Bn〇- l〇h|-〇Η -OH Bn〇- l〇h Bn〇- l〇h

Bn〇一一 l〇CH3 r0H -OH Bn〇- l〇CH3 r〇Ts 一〇H Bn〇- -l〇CH3 Bn〇- lOCH3 其中Bn為苄基，Ts為tosyl ; b)選擇性地與藥學用之酸反應而製得藥學上可接受之鹽Bn〇一一一〇CH3 r0H -OH Bn〇- l〇CH3 r〇Ts 一〇H Bn〇- -l〇CH3 Bn〇- lOCH3 where Bn is benzyl and Ts is tosyl; b) selectively with pharmacy Reacting with an acid to prepare a pharmaceutically acceptable salt

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