7-methoxybenzo[d]thiazole-2-thiol | 908355-82-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 7-methoxybenzo[d]thiazole-2-thiol
• 英文别名: 2-Mercapto-7-methoxy-benzthiazol；7-Methoxy-benzothiazole-2-thiol；7-methoxy-3H-1,3-benzothiazole-2-thione
• CAS: 908355-82-8
• 化学式: C₈H₇NOS₂
• 分子量: 197.282
• InChiKey: FIDWAAQFVRHGAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-methoxybenzo[d]thiazole-2-thiol 在 铁粉 作用下， 以 溶剂黄146 为溶剂， 生成 7-甲氧基苯并[D]噻唑
  参考文献：
  名称：

  Taddei,F. et al., Gazzetta Chimica Italiana, 1965, vol. 95, p. 499 - 506

  摘要：

  DOI：
• 作为产物：
  描述：

  2-氨基-3-硝基苯酚 在 氢溴酸 盐酸 、 硫酸 、 铁粉 、 potassium carbonate 、 copper(I) bromide 、 sodium nitrite 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 7-methoxybenzo[d]thiazole-2-thiol
  参考文献：
  名称：

  7‘-Substituted Benzothiazolothio- and Pyridinothiazolothio-Purines as Potent Heat Shock Protein 90 Inhibitors

  摘要：

  We report on the discovery of benzo- and pyridino-thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice. In vivo efficacy experiments demonstrate that compounds of this class inhibit tumor growth in an N87 human colon cancer xenograft model via oral administration as shown with compound 37 (8-(7-chlorobenzothiazol-2- ylsulfanyl)-9-(2-cyclopropylamino-ethyl)-9H-purin-6-ylamine).

  DOI：

  10.1021/jm051146h

文献信息

• [EN] BICYCLIC HETEROARYL SUBSTITUTED COMPOUNDS<br/>[FR] COMPOSÉS BICYCLIQUES SUBSTITUÉS PAR HÉTÉROARYLE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2018013774A1

  公开（公告）日：2018-01-18

  Disclosed are compounds of Formula (I) to (VIII): (I) (II) (III) (IV) (V) (VI) (VII) (VIII); or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R3 is a bicyclic heteroaryl group substituted with zero to 3 R3a; and R1, R2, R3a, R4, and n are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmaceutical compositions comprising such compounds. These compounds are useful in inhibiting or preventing platelet aggregation, and are useful for the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder.

  公开了公式(I)至(VIII)的化合物：(I) (II) (III) (IV) (V) (VI) (VII) (VIII)；或其立体异构体、互变异构体、药物可接受的盐、溶剂化物或前药，其中R3是与0至3个R3a取代的双环杂芳基团；且R1、R2、R3a、R4和n在此定义。还公开了使用这些化合物作为PAR4抑制剂的方法，以及包含这些化合物的药物组合物。这些化合物用于抑制或预防血小板聚集，用于治疗血栓栓塞障碍或作为血栓栓塞障碍的初级预防。
• 2-AMINOPYRIDINE KINASE INHIBITORS
  申请人：Steinig Arno G.

  公开号：US20090197862A1

  公开（公告）日：2009-08-06

  2-Aminopyridine compounds having the structure of Formula I, and pharmaceutically acceptable salts of these compounds. Compounds of Formula I inhibit the activity of tyrosine kinase enzymes in animals, including humans, and are useful in the treatment and/or prevention of various diseases and conditions. In particular, compounds disclosed herein are inhibitors of kinases, in particular, but not limited to, KDR, Tie-2, Flt3, FGFR3, Ab1, Aurora A, c-Src, IGF-1R, ALK, c-MET, RON, PAK1, PAK2, and TAK1, and can be used in the treatment of proliferative diseases, such as, but not limited to, cancer. The present invention is also directed to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The present invention is further directed to a method of treating a patient having a condition which is mediated by protein kinase activity by administering to the patient a therapeutically effective amount of the above-mentioned pharmaceutical composition.

  具有Formula I结构的2-氨基吡啶化合物，以及这些化合物的药用可接受的盐。Formula I的化合物抑制动物（包括人类）中的酪氨酸激酶酶活性，并可用于治疗和/或预防各种疾病和病况。特别地，本文披露的化合物是激酶抑制剂，特别是但不限于KDR、Tie-2、Flt3、FGFR3、Ab1、Aurora A、c-Src、IGF-1R、ALK、c-MET、RON、PAK1、PAK2和TAK1，并可用于治疗增生性疾病，如但不限于癌症。本发明还涉及一种包含Formula I化合物的药物组合物，或其药用可接受的盐，以及药用可接受的载体的药物组合物。本发明还涉及一种通过向患有由蛋白激酶活性介导的病症的患者投与上述药物组合物的治疗方法。
• Orally Active Purine-Based Inhibitors of Heat Shock Protein 90
  申请人：Kasibhatla R. Srinivas

  公开号：US20070129334A1

  公开（公告）日：2007-06-07

  Novel purine compounds and tautomers and pharmaceutically acceptable salts thereof are described, as are pharmaceutical compositions comprising the same, complexes comprising the same, e.g., HSP90 complexes, and methods of using the same. Methods of using the novel purine compounds of the invention, and tautomers and pharmaceutically acceptable salts thereof, include their use in inhibiting heat shock protein 90's (HSP90's) to thereby treat or prevent HSP90-dependent diseases, e.g., proliferative disorders such as breast cancer.

  本发明描述了新型嘌呤化合物及其互变异构体和药学上可接受的盐，以及包含它们的制药组合物、包含它们的复合物（例如HSP90复合物）和使用它们的方法。使用本发明的新型嘌呤化合物、互变异构体和药学上可接受的盐的方法包括在抑制热休克蛋白90（HSP90）中使用它们，从而治疗或预防HSP90依赖性疾病，例如增生性疾病如乳腺癌。
• 2-aminopyridine kinase inhibitors
  申请人：OSI Pharmaceuticals, LLC

  公开号：US08178668B2

  公开（公告）日：2012-05-15

  2-Aminopyridine compounds having the structure of Formula I, and pharmaceutically acceptable salts of these compounds. Compounds of Formula I inhibit the activity of tyrosine kinase enzymes in animals, including humans, and are useful in the treatment and/or prevention of various diseases and conditions. In particular, compounds disclosed herein are inhibitors of kinases, in particular, but not limited to, KDR, Tie-2, Flt3, FGFR3, Ab1, Aurora A, c-Src, IGF-1R, ALK, c-MET, RON, PAK1, PAK2, and TAK1, and can be used in the treatment of proliferative diseases, such as, but not limited to, cancer. The present invention is also directed to a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. The present invention is further directed to a method of treating a patient having a condition which is mediated by protein kinase activity by administering to the patient a therapeutically effective amount of the above-mentioned pharmaceutical composition.

  具有I式结构的2-氨基吡啶化合物，以及这些化合物的药学上可接受的盐。I式化合物抑制动物（包括人类）中的酪氨酸激酶酶活性，并在治疗和/或预防各种疾病和病况方面有用。特别地，本文披露的化合物是激酶抑制剂，特别是但不限于KDR，Tie-2，Flt3，FGFR3，Ab1，Aurora A，c-Src，IGF-1R，ALK，c-MET，RON，PAK1，PAK2和TAK1，并可用于治疗增殖性疾病，例如但不限于癌症。本发明还涉及一种制备药物组合物的方法，该组合物包括I式化合物或其药学上可接受的盐的治疗有效量以及药学上可接受的载体。本发明还涉及一种通过向患有蛋白激酶活性介导的病症的患者投与上述药物组合物的治疗方法。
• [1,2,4]Triazolo[3,4-<i>b</i>]benzothiazole Scaffold as Versatile Nicotinamide Mimic Allowing Nanomolar Inhibition of Different PARP Enzymes
  作者：Sudarshan Murthy、Maria Giulia Nizi、Mirko M. Maksimainen、Serena Massari、Juho Alaviuhkola、Barbara E. Lippok、Chiara Vagaggini、Sven T. Sowa、Albert Galera-Prat、Yashwanth Ashok、Harikanth Venkannagari、Renata Prunskaite-Hyyryläinen、Elena Dreassi、Bernhard Lüscher、Patricia Korn、Oriana Tabarrini、Lari Lehtiö

  DOI：10.1021/acs.jmedchem.2c01460

  日期：2023.1.26

  nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. The binding mode was studied through analogues and cocrystal structures with TNKS2, PARP2, PARP14, and PARP15. Based on the substitution pattern, we were able to identify 3-amino derivatives 21 (OUL243) and 27 (OUL232) as inhibitors of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14, and PARP15 at nM potencies, with 27 being

  我们将 [1,2,4] 三唑并 [3,4- b ] 苯并噻唑 (TBT) 报告为一种新的抑制剂支架，它与烟酰胺在人类聚-和单-ADP-核糖基化酶的结合口袋中竞争。通过 TNKS2、PARP2、PARP14 和 PARP15 的类似物和共晶结构研究了结合模式。基于取代模式，我们能够将 3-氨基衍生物21 (OUL243) 和27 (OUL232) 鉴定为 nM 效价的单 ART PARP7、PARP10、PARP11、PARP12、PARP14 和 PARP15 抑制剂，其中27是迄今为止描述的最有效的 PARP10 抑制剂（IC 50为 7.8 nM）和第一个报道的 PARP12 抑制剂。相反，羟基衍生物16(OUL245) 抑制对 PARP2 具有选择性的多 ART。支架不具有固有的细胞毒性，抑制剂可以进入细胞并与靶蛋白结合。这与有利的 ADME 特性一起，证明了 TBT 支架在未来针对