(S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid | 1206123-51-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid
• 英文别名: 2-[(3S)-7-[[4-cyclopentyl-3-(trifluoromethyl)phenyl]methoxy]-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]acetic acid
• CAS: 1206123-51-4
• 化学式: C₂₆H₂₆F₃NO₃
• 分子量: 457.493
• InChiKey: MVGWUTBTXDYMND-KRWDZBQOSA-N

物化性质

• 沸点：
  621.4±50.0 °C(Predicted)
• 密度：
  1.326±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  62.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid 在 calcium acetate 作用下， 以 水 、 乙腈 为溶剂， 生成 (S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid calcium salt
  参考文献：
  名称：

  [EN] SUBSTITUTED 1,2,3,4- TETRAHYDROCYCLOPENTA[b]INDOL-3-YL) ACETIC ACID DERIVATIVES USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS
  [FR] DÉRIVÉS DE L'ACIDE 1,2,3,4-TÉTRAHYDROCYCLOPENTA[B]INDOL-3-YLE ACÉTIQUE SUBSTITUÉ UTILISÉS DANS LE TRAITEMENT DES MALADIES AUTO-IMMUNES ET INFLAMMATOIRES

  摘要：

  本发明涉及某些替代的1,2,3,4-四氢环戊基吲哚-3-基乙酸衍生物的化合物（Ia）及其药用盐，这些化合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该发明化合物的药物组合物，以及使用该发明化合物和组合物治疗S1P1受体相关疾病的方法，例如银屑病、类风湿关节炎、克罗恩病、移植排斥、多发性硬化症、系统性红斑狼疮、溃疡性结肠炎、I型糖尿病、痤疮、微生物感染或疾病以及病毒感染或疾病。

  公开号：

  WO2010011316A1
• 作为产物：
  描述：

  2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid 在 三氟乙酸 作用下， 以 正己烷 、 异丙醇 为溶剂， 生成 (S)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid 、 (R)-2-(7-(4-环戊基-3-(三氟甲基)苄氧基)-1,2,3,4-四氢环戊并[b]吲哚-3-基)乙酸
  参考文献：
  名称：

  [EN] SUBSTITUTED 1,2,3,4- TETRAHYDROCYCLOPENTA[b]INDOL-3-YL) ACETIC ACID DERIVATIVES USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS
  [FR] DÉRIVÉS DE L'ACIDE 1,2,3,4-TÉTRAHYDROCYCLOPENTA[B]INDOL-3-YLE ACÉTIQUE SUBSTITUÉ UTILISÉS DANS LE TRAITEMENT DES MALADIES AUTO-IMMUNES ET INFLAMMATOIRES

  摘要：

  本发明涉及某些替代的1,2,3,4-四氢环戊基吲哚-3-基乙酸衍生物的化合物（Ia）及其药用盐，这些化合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该发明化合物的药物组合物，以及使用该发明化合物和组合物治疗S1P1受体相关疾病的方法，例如银屑病、类风湿关节炎、克罗恩病、移植排斥、多发性硬化症、系统性红斑狼疮、溃疡性结肠炎、I型糖尿病、痤疮、微生物感染或疾病以及病毒感染或疾病。

  公开号：

  WO2010011316A1

文献信息

• [EN] PROCESSES FOR THE PREPARATION OF (R)-2-(7-(4-CYCLOPENTYL-3-(TRIFLUOROMETHYL)BENZYLOXY)-1,2,3,4-TETRAHYDROCYCLOPENTA[B]INDOL-3-YL)ACETIC ACID AND SALTS THEREOF<br/>[FR] PROCÉDÉS DE PRÉPARATION D'ACIDE (R)-2-(7-(4-CYCLOPENTYL-3-(TRIFLUOROMÉTHYL)BENZYLOXY)-1,2,3,4-TÉTRAHYDROCYCLOPENTA]INDOL-3-YL) ACÉTIQUE ET DE SES SELS
  申请人：ARENA PHARM INC

  公开号：WO2011094008A1

  公开（公告）日：2011-08-04

  The present invention relates to processes and intermediates useful in the preparation of of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid of Formula (Ia) and salts thereof, an S1P1 receptor modulator that is useful in the treatment of S1P1 receptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditions characterized by an underlying defect in vascular integrity or that are associated with angiogenesis such as may be pathologic (e.g., as may occur in inflammation, tumor development and atherosclerosis).

  本发明涉及用于制备（R）-2-(7-(4-环戊基-3-(三氟甲基)苄氧基)-1,2,3,4-四氢环戊[b]吲哚-3-基)乙酸及其盐的过程和中间体，该化合物是S1P1受体调节剂，用于治疗S1P1受体相关疾病，例如由淋巴细胞介导的疾病和疾病，移植排斥反应，自身免疫疾病和疾病，炎症性疾病和疾病（例如，急性和慢性炎症症状），癌症，以及具有血管完整性基础缺陷或与血管生成相关的疾病和疾病，如可能是病理性的（例如，在炎症、肿瘤发展和动脉粥样硬化中可能发生的情况）。
• SUBSTITUTED 1,2,3,4-TETRAHYDROCYCLOPENTA[B]INDOL-3-YL)ACETIC ACID DERIVATIVES USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS
  申请人：Jones Robert M.

  公开号：US20110130409A1

  公开（公告）日：2011-06-02

  The present invention relates to certain substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic 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 receptor-associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, microbial infections or diseases and viral infections or diseases.

  本发明涉及某些取代的1,2,3,4-四氢环戊[b]吲哚-3-基乙酸衍生物（Ia式）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。本发明还提供了含有该发明化合物的药物组合物，以及使用该化合物和组合物治疗S1P1受体相关疾病的方法，例如牛皮癣、类风湿性关节炎、克隆病、移植排斥、多发性硬化症、系统性红斑狼疮、溃疡性结肠炎、1型糖尿病、痤疮、微生物感染或疾病和病毒感染或疾病。
• SUBSTITUTED 1,2,3,4-TETRAHYDROCYCLOPENTA[b]INDOL-3-YL)ACETIC ACID DERIVATIVES USEFUL IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISORDERS
  申请人：Arena Pharmaceuticals, Inc.

  公开号：US20140038987A1

  公开（公告）日：2014-02-06

  The present invention relates to certain substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic 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 receptor-associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, microbial infections or diseases and viral infections or diseases.

  本发明涉及某些取代的1,2,3,4-四氢环戊[b]吲哚-3-基)乙酸衍生物(Ia式)及其药学上可接受的盐，这些衍生物具有有用的药理学特性，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，并且提供了使用本发明化合物和组合物治疗S1P1受体相关疾病的方法，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、痤疮、微生物感染或疾病和病毒感染或疾病。
• PROCESSES FOR THE PREPARATION OF (R)-2-(7-(4-CYCLOPENTYL-3-(TRIFLUOROMETHYL)BENZYLOXY)-1,2,3,4-TETRAHYDROCYCLOPENTA[B]INDOL-3-YL)ACETIC ACID AND SALTS THEREOF
  申请人：ARENA PHARMACEUTICALS, INC.

  公开号：US20140357690A1

  公开（公告）日：2014-12-04

  The present invention relates to processes and intermediates useful in the preparation of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid of Formula (Ia) and salts thereof, an S1P1 receptor modulator that is useful in the treatment of S1P1 receptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditions characterized by an underlying defect in vascular integrity or that are associated with angiogenesis such as may be pathologic (e.g., as may occur in inflammation, tumor development and atherosclerosis).

  本发明涉及用于制备式(Ia)的(R)-2-(7-(4-环戊基-3-(三氟甲基)苯基氧基)-1,2,3,4-四氢-环戊[b]吲哚-3-基)乙酸及其盐的中间体和工艺，该化合物是一种S1P1受体调节剂，可用于治疗S1P1受体相关疾病和紊乱，例如淋巴细胞介导的疾病和紊乱、移植排斥、自身免疫性疾病和紊乱、炎性疾病和紊乱（例如急性和慢性炎症病症）、癌症以及具有血管完整性基础缺陷或与血管生成有关的病症，如可能是病理性的（例如可能发生在炎症、肿瘤发展和动脉粥样硬化中）。
• CRYSTALLINE L-ARGININE SALT OF (R)-2-(7-(4-CYCLOPENTYL-3-(TRIFLUOROMETHYL)BENZYLOXY)-1,2,3,4-TETRAHYDROCYCLO-PENTA[B]INDOL-3-YL)ACETIC ACID FOR USE IN SIPI RECEPTOR-ASSOCIATED DISORDERS
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP3939965A1

  公开（公告）日：2022-01-19

  The present invention relates to, inter alia, a novel crystalline free-plate habit or morphology, processes for preparing the crystalline free-plate habit, and uses of the crystalline free-plate habit of the L-arginine salt of (R)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid (Compound 1) in the treatment of S1P1 receptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditions characterized by an underlying defect in the vascular integrity or that are associated with angiogenesis such as may be pathologic (e.g., as may occur in inflammation, tumor development, and atherosclerosis).

  本发明主要涉及一种新的自由平板结晶习性或形态，制备该自由平板结晶习性的工艺，以及(R)-2-(7-(4-环戊基-3-(三氟甲基)苄氧基)-1、(R)-2-(7-(4-环戊基-3-(三氟甲基)苄氧基)-1,2,3,4-四氢环戊二烯并[b]吲哚-3-基)乙酸的 L-精氨酸盐（化合物 1），用于治疗 S1P1 受体相关疾病，例如由淋巴细胞介导的疾病和失调、移植排斥、自身免疫性疾病和失调、炎症性疾病和失调（如淋巴结炎）。g.,例如，急性和慢性炎症）、癌症，以及以血管完整性的潜在缺陷为特征的疾病或与血管生成有关的疾病，如病理上的血管生成（如可能发生在炎症、肿瘤发生和动脉粥样硬化中的血管生成）。