2-(7-(5-(3-cyano-4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid | 1174512-64-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(7-(5-(3-cyano-4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid
• 英文别名: 2-[6-[5-[3-cyano-4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-3-yl]-2,3-dihydro-1H-pyrrolo[1,2-a]indol-3-yl]acetic acid
• CAS: 1174512-64-1
• 化学式: C₂₃H₁₅F₃N₄O₄
• 分子量: 468.392
• InChiKey: LHJYAKFEGXBYOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  tert-butyl 2-(7-(5-(3-cyano-4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate 在 茴香硫醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 2-(7-(5-(3-cyano-4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid
  参考文献：
  名称：

  [EN] DIHYDRO- 1H- PYRROLO [1,2-A] INDOL-1-YL CARBOXYLIC DERIVATIVES WHICH ACT AS S1P1 AGONISTS
  [FR] DÉRIVÉS CARBOXYLIQUES DIHYDRO-1H-PYRROLO[1,2-A]INDOL-1-YLE AGISSANT COMME DES AGONISTES DE S1P1

  摘要：

  本发明涉及一些(1,2,4-噁二唑-3-基)-2,3-二氢-1H-吡咯[1,2-a]吲哚-1-基羧酸衍生物的化学式(Ia)及其药用可接受的盐，这些衍生物展示出有用的药理特性，例如作为S1P1受体的激动剂。本发明还提供了含有本发明化合物的药物组合物，以及使用本发明化合物和组合物治疗S1P1相关疾病的方法，例如牛皮癣、类风湿关节炎、克罗恩病、移植排斥反应、多发性硬化、系统性红斑狼疮、溃疡性结肠炎、I型糖尿病、败血症、心肌梗死、缺血性中风、痤疮、微生物感染或疾病以及病毒感染或疾病。

  公开号：

  WO2009094157A1

文献信息

• DIHYDRO-1H-PYRROLO[1,2-A]INDOL-1-YL CARBOXYLIC ACID DERIVATIVES WHICH ACT AS S1P1 AGONISTS
  申请人：Jones Robert M.

  公开号：US20100292233A1

  公开（公告）日：2010-11-18

  The present invention relates to certain (1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl carboxylic acid derivatives of Formula (Ia) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1 associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, sepsis, myocardial infarction, ischemic stroke, acne, microbial infections or diseases and viral infections or diseases.

  本发明涉及公式（Ia）中的某些（1,2,4-噁二唑-3-基）-2,3-二氢-1H-吡咯并[1,2-a]吲哚-1-基羧酸衍生物及其药学上可接受的盐，其具有有用的药理特性，例如作为S1P1受体激动剂。本发明还提供了包含该发明化合物的制药组合物，并提供了使用该化合物和组合物治疗S1P1相关疾病的方法，例如牛皮癣、类风湿性关节炎、克罗恩病、移植排斥、多发性硬化症、全身性红斑狼疮、溃疡性结肠炎、1型糖尿病、败血症、心肌梗塞、缺血性中风、痤疮、微生物感染或疾病和病毒感染或疾病。
• Fused tricyclic indoles as S1P1 agonists with robust efficacy in animal models of autoimmune disease
  作者：Daniel J. Buzard、Sangdon Han、Luis Lopez、Andrew Kawasaki、Jeanne Moody、Lars Thoresen、Brett Ullman、Juerg Lehmann、Imelda Calderon、Xiuwen Zhu、Tawfik Gharbaoui、Dipanjan Sengupta、Ashwin Krishnan、Yinghong Gao、Jeff Edwards、Jeremy Barden、Michael Morgan、Khawja Usmani、Chuan Chen、Abu Sadeque、Jayant Thatte、Michelle Solomon、Lixia Fu、Kevin Whelan、Ling Liu、Hussien Al-Shamma、Joel Gatlin、Minh Le、Charles Xing、Sheryll Espinola、Robert M. Jones

  DOI：10.1016/j.bmcl.2012.04.129

  日期：2012.7

  Two series of fused tricyclic indoles were identified as potent and selective S1P(1) agonists. In vivo these agonists produced a significant reduction in circulating lymphocytes which translated into robust efficacy in several rodent models of autoimmune disease. Importantly, these agonists were devoid of any activity at the S1P(3) receptor in vitro, and correspondingly did not produce S1P(3) mediated bradycardia in telemeterized rat. (C) 2012 Elsevier Ltd. All rights reserved.
• DIHYDRO- 1H- PYRROLO [1,2-A]INDOL-1-YL CARBOXYLIC DERIVATIVES WHICH ACT AS S1P1 AGONISTS
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP2252615A1

  公开（公告）日：2010-11-24
• [EN] DIHYDRO- 1H- PYRROLO [1,2-A] INDOL-1-YL CARBOXYLIC DERIVATIVES WHICH ACT AS S1P1 AGONISTS<br/>[FR] DÉRIVÉS CARBOXYLIQUES DIHYDRO-1H-PYRROLO[1,2-A]INDOL-1-YLE AGISSANT COMME DES AGONISTES DE S1P1
  申请人：ARENA PHARM INC

  公开号：WO2009094157A1

  公开（公告）日：2009-07-30

  The present invention relates to certain (1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl carboxylic acid derivatives of Formula (Ia) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1 associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, sepsis, myocardial infarction, ischemic stroke, acne, microbial infections or diseases and viral infections or diseases.

  本发明涉及一些(1,2,4-噁二唑-3-基)-2,3-二氢-1H-吡咯[1,2-a]吲哚-1-基羧酸衍生物的化学式(Ia)及其药用可接受的盐，这些衍生物展示出有用的药理特性，例如作为S1P1受体的激动剂。本发明还提供了含有本发明化合物的药物组合物，以及使用本发明化合物和组合物治疗S1P1相关疾病的方法，例如牛皮癣、类风湿关节炎、克罗恩病、移植排斥反应、多发性硬化、系统性红斑狼疮、溃疡性结肠炎、I型糖尿病、败血症、心肌梗死、缺血性中风、痤疮、微生物感染或疾病以及病毒感染或疾病。