CN104788457B - 新型抗寄生虫吡嗪异喹啉衍生物 - Google Patents
新型抗寄生虫吡嗪异喹啉衍生物 Download PDFInfo
- Publication number
- CN104788457B CN104788457B CN201510117838.3A CN201510117838A CN104788457B CN 104788457 B CN104788457 B CN 104788457B CN 201510117838 A CN201510117838 A CN 201510117838A CN 104788457 B CN104788457 B CN 104788457B
- Authority
- CN
- China
- Prior art keywords
- compound
- pharmaceutically acceptable
- pharmaceutical composition
- yuan
- drug
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- GPBRIMOJKVDGLP-UHFFFAOYSA-N isoquinoline;pyrazine Chemical class C1=CN=CC=N1.C1=NC=CC2=CC=CC=C21 GPBRIMOJKVDGLP-UHFFFAOYSA-N 0.000 title description 4
- 230000002141 anti-parasite Effects 0.000 title description 2
- 239000003096 antiparasitic agent Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 25
- 239000003814 drug Substances 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 8
- 241000242677 Schistosoma japonicum Species 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- 208000030852 Parasitic disease Diseases 0.000 claims description 5
- 241001327965 Clonorchis sinensis Species 0.000 claims description 4
- 241000242678 Schistosoma Species 0.000 claims description 3
- 241000242541 Trematoda Species 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 230000002147 killing effect Effects 0.000 claims 4
- 241000935974 Paralichthys dentatus Species 0.000 claims 1
- 244000045947 parasite Species 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 abstract description 5
- -1 general structure I Chemical class 0.000 abstract description 3
- 150000002576 ketones Chemical class 0.000 abstract description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 2
- 201000004409 schistosomiasis Diseases 0.000 description 15
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 6
- 238000003760 magnetic stirring Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 206010033794 paragonimiasis Diseases 0.000 description 3
- FSVJFNAIGNNGKK-UHFFFAOYSA-N 2-[cyclohexyl(oxo)methyl]-3,6,7,11b-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4-one Chemical compound C1C(C2=CC=CC=C2CC2)N2C(=O)CN1C(=O)C1CCCCC1 FSVJFNAIGNNGKK-UHFFFAOYSA-N 0.000 description 2
- 241000238631 Hexapoda Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- JBDSSBMEKXHSJF-UHFFFAOYSA-N cyclopentanecarboxylic acid Chemical compound OC(=O)C1CCCC1 JBDSSBMEKXHSJF-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 229960002957 praziquantel Drugs 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000242722 Cestoda Species 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical class ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 241000565675 Oncomelania Species 0.000 description 1
- 241000242680 Schistosoma mansoni Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 206010048282 zoonosis Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种如结构通式I的化合物，其中，A选自苯环；B选自饱和氮杂环，包括五元、六元、七元饱和氮杂环；C选自饱和氮杂环，包括五元、六元、七元饱和氮杂环，可以是酮或非酮化合物；D选自饱和环，包括三元、四元、五元、六元和七元饱和环。以及涉及如上所述化合物的应用、药物组合物和药物。
Description
技术领域
本发明涉及一种治疗寄生虫疾病的新型吡嗪异喹啉衍生物，特别涉及一种治疗寄生虫疾病包括但不限于血吸虫、绦虫、囊虫、华支睾吸虫、肺吸虫和姜片虫引起的人畜共患性疾病的包括一种吡嗪异喹啉衍生物组分的药物组合和药物。
背景技术
血吸虫病是由于感染三种主要的血吸虫(曼氏血吸虫、埃及血吸虫和日本血吸虫)而引起的流行病。40年来，吡喹酮仍然是广泛用于防治人和动物各种血吸虫成虫感染的唯一有效药物。由于它的大量和长期使用，目前已经产生药物抗性；而针对血吸虫幼虫感染的血吸虫病至今仍无有效药物治疗。据世界卫生组织披露全球有2亿人感染血吸虫病，有约6亿人受感染威胁，血吸虫病的高发病人数有2千万，每年有至少280000人死于血吸虫病。而***和国家***下发的“全国综合治理血吸虫病‘十五’计划”数据表明，我国目前尚未控制血吸虫病传播的108个县集中分布在湖沼地区和大山区，动物宿主众多，钉螺分布广泛，受环境因素影响很大，防治工作特别困难，重复感染依然十分严重，疫情处于很不稳定状态。面对如此众多的血吸虫病感染人群仅吡喹酮一种化学药物是很不相称的，因此亟需研制新的抗血吸虫药物。
发明内容
一种通式I的化合物，其药用上适用于人和动物的各种盐，及其各种异构体和氮氧化合物。结构通式如式I，
其中，
A是不饱和环，包括苯环，吡啶环和氮氧偶极吡啶环；
B是饱和氮杂环，包括五元，六元，和七元饱和氮杂环，B环上可以由C1-C4烷基取代，或形成3-5元饱和并环；
C是饱和氮杂环，包括五元，六元，和七元饱和氮杂环，可以是酮或非酮化合物；
D是饱和环，包括三元，四元，五元，六元，和七元饱和环；
A选自如下基团：
B+C选自如下基团：
D选自如下基团：
其中优选的但不限于的化合物为：
本发明化合物出乎意料地显示适于治疗寄生虫疾病，尤其包括血吸虫、绦虫、囊虫、华支睾吸虫、肺吸虫、姜片虫引起的人畜共患性疾病.本发明也涉及将上文定义的通式I的化合物，将其药学上接受的酸或碱加成盐，包括季盐，立体化学异构形式，N-氧化合物形式用做药，以及下述任何药物组合物在制备用于治疗寄生虫疾病，包括血吸虫、绦虫、囊虫、华支睾吸虫、肺吸虫、姜片虫引起的人畜共患性疾病的药物中的用途。
因此，本发明另一方面提供一种治疗患有寄生虫疾病(包括血吸虫疾病)的方法，该方法包括治疗有效量的本发明化合物或药物组合物给予患者或患蓄。
本发明也涉及组合物，其包含药学上可接受的载体和作为活性成分的治疗有效量的本发明化合物。本发明化合物可被调配成用于给药目的的不同药物形式。作为适当组合物的例证的是全身给药药物通常所采用的所有组合物。为制备本发明药物组合物，有效量的特定化合物(任选以加成盐形式)作为活性成分与药物可接受载体紧密组合，取决于给药所需的制剂形式，所述载体可采取多种形式。这些药物组合物宜为特别是适合口服给药或胃肠外注射的单一剂量形式。例如，在制备口服剂型的组合物时，在口服液体制剂如混悬剂，糖浆剂，乳剂和溶液剂的情况下，可以采用任何平常的药物介质，如水，乙二醇，油，醇等；或者在粉末剂，丸剂，胶囊剂和片剂的情况下，采用固体载体例如淀粉，糖，高岭土，稀释剂，粘合剂等。
取决于给药的方式，所述药物组合优选包括0.05-99％重量，更优选0.1-70％重量的活性成分，以及优选1-99.95％重量，更优选30-99.9％重量的药学上可接受的载体，所有百分比均基于总组合物计算。
具体实施方式
实施例一典型化合物1-3的制备：
向装有磁力搅拌的圆底烧瓶中加入1-1(188mg，1mmol)，环己甲酸(128mg，1mmol)，EDCI(211mg，1.1mmol)和DMAP(139mg，1.1mmol)。室温下搅拌过夜，用1％盐酸水和饱和碳酸钠溶液交替洗涤，最后用水洗。无水硫酸镁干燥后浓缩得白色固体.Mp132-135(277mg，收率93％)。
向装有磁力搅拌的圆底烧瓶中加入1-1(188mg，1mmol)，环戊甲酸(114mg，1mmol)，EDCI(211mg，1.1mmol)和DMAP(139mg，1.1mmol)。室温下搅拌过夜，用1％盐酸水和饱和碳酸钠溶液交替洗涤，最后用水洗。无水硫酸镁干燥后浓缩得白色固体Mp128-130(256mg，收率90.14％)。
向装有磁力搅拌的圆底烧瓶中加入1-1(188mg，1mmol)，环庚甲酸(142mg，1mmol)，EDCI(211mg，1.1mmol)和DMAP(139mg，1.1mmol)。室温下搅拌过夜，用1％盐酸水和饱和碳酸钠溶液交替洗涤，最后用水洗。无水硫酸镁干燥后浓缩得白色固体.Mp137-139(287mg，收率92％)。
实施例二典型化合物10-12的制备：
向装有磁力搅拌的圆底烧瓶中加入10-1(232mg，1mmol)，环己甲酸(128mg，1mmol)，EDCI(211mg，1.1mmol)和DMAP(139mg，1.1mmol)。室温下搅拌过夜，用1％盐酸水和饱和碳酸钠溶液交替洗涤，最后用水洗。无水硫酸镁干燥后浓缩得白色固体.Mp143-146(324mg，收率95％)。
向装有磁力搅拌的圆底烧瓶中加入10-1(232mg，1mmol)，环庚甲酸(142mg，1mmol)，EDCI(211mg，1.1mmol)和DMAP(139mg，1.1mmol)。室温下搅拌过夜，用1％盐酸水和饱和碳酸钠溶液交替洗涤，最后用水洗。无水硫酸镁干燥后浓缩得白色固体.Mp138--141(295mg，收率90％)。
向装有磁力搅拌的圆底烧瓶中加入10-1(232mg，1mmol)，环庚甲酸(142mg，1mmol)，EDCI(211mg，1.1mmol)和DMAP(139mg，1.1mmol)。室温下搅拌过夜，用1％盐酸水和饱和碳酸钠溶液交替洗涤，最后用水洗。无水硫酸镁干燥后浓缩得白色固体.Mp149-153(316mg，收率89％)。
实施例三 生物学效应
测定化合物抗日本血吸虫的体外方法：成虫体外培养：采集活的雄性成虫置于DMEM培养液(10条/3ml/皿)中，分组加药。每皿分别加入化合物各3ul，终浓度为50(mol/ml，对照组加DMS03(1(参考其他实验组加药最高剂量)。加药后充分摇匀，放入37℃、5％CO：培养箱中。培养过夜(16h)后用生理盐水洗涤虫体3次，加入新鲜培养液，在体视显微镜下观察培养.24h～72h后的血吸虫活力状态，并影像记录。结果见表1。
表1
| 化合物 | 虫数 | 死亡率等级 | 化合物 | 虫数 | 死亡率等级 |
| 1 | 20 | A | 35 | 20 | A |
| 4 | 20 | A | 37 | 20 | A |
| 7 | 20 | A | 40 | 20 | A |
| 13 | 20 | A | 43 | 20 | A |
| 18 | 20 | A | 46 | 20 | A |
| 19 | 20 | A | 50 | 20 | A |
| 21 | 20 | A | 54 | 20 | A |
| 22 | 20 | A | 57 | 20 | A |
| 24 | 20 | A | 62 | 20 | A |
| 28 | 20 | A | 64 | 20 | A |
| 29 | 20 | A | 66 | 20 | A |
| 30 | 20 | A | 67 | 20 | A |
| 34 | 20 | A | 69 | 20 | A |
表中死亡率等级：A为100-80％。
Claims (11)
1.一种化合物，其特征在于，所述化合物选自如结构式4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、22、23、24、31、32和33的化合物中的至少一种，
2.根据权利要求1所述的化合物在用于制备预防或治疗寄生虫病的药物中的用途，其中所述寄生虫选自血吸虫、绦虫、囊虫、华支睾吸虫、肺吸虫和姜片虫中的至少一种。
3.一种如权利要求1所述的化合物的药学上可接受的盐。
4.一种对日本血吸虫有杀灭作用的药物组合物，其特征在于，所述药物组合物的活性成分包括如权利要求1所述的化合物。
5.根据权利要求4所述的药物组合物，其特征在于，所述组合物还包含药学上可接受的载体。
6.一种对日本血吸虫有杀灭作用的药物组合物，其特征在于，所述药物组合物的活性成分包括如权利要求3所述的化合物的药学上可接受的盐。
7.根据权利要求6所述的药物组合物，其特征在于，所述组合物还包含药学上可接受的载体。
8.一种对日本血吸虫有杀灭作用的药物，其特征在于，所述药物的活性成分包括如权利要求1所述的化合物。
9.根据权利要求8所述的药物，其特征在于，所述药物还包含药学上可接受的载体。
10.一种对日本血吸虫有杀灭作用的药物，其特征在于，所述药物的活性成分包括如权利要求3所述的化合物的药学上可接受的盐。
11.根据权利要求10所述的药物，其特征在于，所述药物还包含药学上可接受的载体。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510117838.3A CN104788457B (zh) | 2011-05-31 | 2011-05-31 | 新型抗寄生虫吡嗪异喹啉衍生物 |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510117838.3A CN104788457B (zh) | 2011-05-31 | 2011-05-31 | 新型抗寄生虫吡嗪异喹啉衍生物 |
| CN201110154047.XA CN102267998B (zh) | 2011-05-31 | 2011-05-31 | 新型抗寄生虫吡嗪异喹啉衍生物 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201110154047.XA Division CN102267998B (zh) | 2011-05-31 | 2011-05-31 | 新型抗寄生虫吡嗪异喹啉衍生物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104788457A CN104788457A (zh) | 2015-07-22 |
| CN104788457B true CN104788457B (zh) | 2017-08-25 |
Family
ID=45050475
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510117838.3A Expired - Fee Related CN104788457B (zh) | 2011-05-31 | 2011-05-31 | 新型抗寄生虫吡嗪异喹啉衍生物 |
| CN201510117197.1A Expired - Fee Related CN104844606B (zh) | 2011-05-31 | 2011-05-31 | 抗寄生虫吡嗪异喹啉衍生物 |
| CN201110154047.XA Expired - Fee Related CN102267998B (zh) | 2011-05-31 | 2011-05-31 | 新型抗寄生虫吡嗪异喹啉衍生物 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510117197.1A Expired - Fee Related CN104844606B (zh) | 2011-05-31 | 2011-05-31 | 抗寄生虫吡嗪异喹啉衍生物 |
| CN201110154047.XA Expired - Fee Related CN102267998B (zh) | 2011-05-31 | 2011-05-31 | 新型抗寄生虫吡嗪异喹啉衍生物 |
Country Status (1)
| Country | Link |
|---|---|
| CN (3) | CN104788457B (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102321088A (zh) * | 2011-08-03 | 2012-01-18 | 威海秀水药物研发有限公司 | 一种新型抗血吸虫化合物 |
| CN113754666A (zh) * | 2021-09-07 | 2021-12-07 | 凯美克(上海)医药科技有限公司 | 一种苯并吡嗪类化合物及其合成方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3472678D1 (de) * | 1983-07-18 | 1988-08-18 | Beecham Group Plc | Benzazepine and benzoxazepine derivatives |
| DE3619030A1 (de) * | 1986-06-06 | 1987-12-10 | Bayer Ag | Topisch anwendbare zubereitungen |
| CN100503582C (zh) * | 2005-03-01 | 2009-06-24 | 江苏工业学院 | 吡喹酮合成工艺 |
-
2011
- 2011-05-31 CN CN201510117838.3A patent/CN104788457B/zh not_active Expired - Fee Related
- 2011-05-31 CN CN201510117197.1A patent/CN104844606B/zh not_active Expired - Fee Related
- 2011-05-31 CN CN201110154047.XA patent/CN102267998B/zh not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN102267998A (zh) | 2011-12-07 |
| CN104788457A (zh) | 2015-07-22 |
| CN104844606A (zh) | 2015-08-19 |
| CN104844606B (zh) | 2017-03-01 |
| CN102267998B (zh) | 2015-05-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11760735B2 (en) | Compounds and compositions for treating conditions associated with NLRP activity | |
| WO2017162108A1 (zh) | 一种柱芳烃类复合物、其制备方法、药物组合物和用途 | |
| ES2644870T3 (es) | Derivados de oxatiazina como agentes antibacterianos y anticancerígenos | |
| Xiao et al. | Research and development of antischistosomal drugs in the People's Republic of China: a 60-year review | |
| CN104736202B (zh) | 用于抑制肌成束蛋白的方法 | |
| CN101616917A (zh) | 吡啶并[2,3-d]嘧啶以及它们作为激酶抑制剂的用途 | |
| KR20170113546A (ko) | 옥사티아진-유사 화합물의 제조방법 | |
| EP3498274B1 (en) | Application of phosphodiesterase 4 inhibitor zl-n-91 in preparation of medicament for treating prostate cancer proliferation and metastasis | |
| KR20150081422A (ko) | mTOR 경로 관련 질병 치료를 위한 화합물 | |
| CN108530444A (zh) | 一种新型nampt和ido双重抑制剂及其制备方法和医药用途 | |
| CN104788457B (zh) | 新型抗寄生虫吡嗪异喹啉衍生物 | |
| CN102218140B (zh) | 丹酚酸b和昔布类药物联合用药的抗肿瘤效果 | |
| CN106632133B (zh) | 噻唑类衍生物及其制备方法与应用 | |
| CN107820495A (zh) | 靶向epha4的配体结合域的新型epha4抑制剂 | |
| CN102432607A (zh) | 一种吡嗪异喹啉衍生物在制备治疗血吸虫药物中的应用 | |
| TWI542348B (zh) | 含４－乙醯基－安卓奎諾－ｂ之組合物用於製備抑制癌細胞生長之藥物的用途 | |
| US20190083443A1 (en) | Ingenol compounds and use thereof in anti-hiv latency treatment | |
| CN106668012A (zh) | 含氮杂环芳香酯类化合物在制备抗柯萨奇病毒b3型的药物中的应用 | |
| JP2022542449A (ja) | Ｓｔａｔ３二機能性リン酸化部位を標的とするトリアロマティック化合物のクラスおよびその応用 | |
| Yang et al. | Natural product honokiol exhibits antiviral effects against Micropterus salmoides rhabdovirus (MSRV) both in vitro and in vivo | |
| US10064843B2 (en) | Bis-amide derivative and use thereof | |
| WO2021223664A1 (en) | Methods for treating coronavirus infections | |
| CN110384694B (zh) | 一种xenicane型二萜化合物在制备抗氧化神经保护药物中的应用 | |
| US11891396B1 (en) | 5-substituted pyrido[3″,4″:4′,5′]pyrrolo[3′,2′:4,5]imidazo[1,2-a]pyrazine compounds as CK2 inhibitors | |
| US11970499B1 (en) | Pyrazolo[1,5-c]pyrimidine compounds as CK2 inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170825 Termination date: 20180531 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |