(5-chloro-2,2',5'-trioxo-spiro[indole-3,3'-pyrrolidin]-1-yl)-acetic acid tert-butyl ester | 916047-76-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (5-chloro-2,2',5'-trioxo-spiro[indole-3,3'-pyrrolidin]-1-yl)-acetic acid tert-butyl ester
• 英文别名: (5-Chloro-2,2',5'-trioxo-spiro[indole-3,3'-pyrrolidin]-1-yl)acetic acid tert-butyl ester；tert-butyl 2-(5-chloro-2,2',5'-trioxospiro[indole-3,3'-pyrrolidine]-1-yl)acetate
• CAS: 916047-76-2
• 化学式: C₁₇H₁₇ClN₂O₅
• 分子量: 364.785
• InChiKey: ZGLOJAYUKCUUDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  92.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5-chloro-2,2',5'-trioxo-spiro[indole-3,3'-pyrrolidin]-1-yl)-acetic acid tert-butyl ester 、 (1-溴乙基)苯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 Tert-butyl 2-[5-chloro-2,2',5'-trioxo-1'-(1-phenylethyl)spiro[indole-3,3'-pyrrolidine]-1-yl]acetate
  参考文献：
  名称：

  Discovery of a New Class of Potent, Selective, and Orally Bioavailable CRTH2 (DP2) Receptor Antagonists for the Treatment of Allergic Inflammatory Diseases

  摘要：

  A novel chemical class of potent chemoattractant receptor-homologous expressed on Th2 lymphocytes (CRTH2 or DP2) antagonists is reported. An initial and moderately potent spiro-indolinone compound (5) was found during a high-throughput screening campaign. Structure - activity relationship (SAR) investigation around the carboxylic acid group revealed that changes in this part of the molecule could lead to a reversal of functional activity, yielding weakly potent agonists. SAR investigation of the succinimide functional group led to the discovery of several single-digit nanomolar antagonists. The potency of these compounds was confirmed in a human eosinophil chemotaxis assay. Moreover, compounds (R)-58 and (R)-71 were shown to possess pharmacokinetic properties suitable for development as an orally bioavailable drug.

  DOI：

  10.1021/jm701383e
• 作为产物：
  描述：

  5-chloro-1H-spiro[indole-3,3'-pyrrolidine]-2,2',5'-trione 、 溴乙酸叔丁酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以95%的产率得到(5-chloro-2,2',5'-trioxo-spiro[indole-3,3'-pyrrolidin]-1-yl)-acetic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of a New Class of Potent, Selective, and Orally Bioavailable CRTH2 (DP2) Receptor Antagonists for the Treatment of Allergic Inflammatory Diseases

  摘要：

  A novel chemical class of potent chemoattractant receptor-homologous expressed on Th2 lymphocytes (CRTH2 or DP2) antagonists is reported. An initial and moderately potent spiro-indolinone compound (5) was found during a high-throughput screening campaign. Structure - activity relationship (SAR) investigation around the carboxylic acid group revealed that changes in this part of the molecule could lead to a reversal of functional activity, yielding weakly potent agonists. SAR investigation of the succinimide functional group led to the discovery of several single-digit nanomolar antagonists. The potency of these compounds was confirmed in a human eosinophil chemotaxis assay. Moreover, compounds (R)-58 and (R)-71 were shown to possess pharmacokinetic properties suitable for development as an orally bioavailable drug.

  DOI：

  10.1021/jm701383e

文献信息

• Tricyclic spiro derivatives as CRTH2 modulators
  申请人：Schwarz Matthias

  公开号：US20090318486A1

  公开（公告）日：2009-12-24

  The present invention is related to the use of spiro derivatives of Formula (I) for the treatment and/or prevention of allergic diseases, inflammatory dermatoses and other diseases with an inflammatory component. Specifically, the present invention is related to the use of spiro derivatives for the modulation of CRTH2 activity.

  本发明涉及使用式(I)的螺环衍生物用于治疗和/或预防过敏性疾病、炎症性皮肤病和其他具有炎症成分的疾病。具体而言，本发明涉及使用螺环衍生物来调节CRTH2活性。
• WO2006/125784
  申请人：——

  公开号：——

  公开（公告）日：——
• TRICYCLIC SPIRO DERIVATIVES AS CRTH2 MODULATORS
  申请人：Merck Serono SA

  公开号：EP1891075B1

  公开（公告）日：2011-10-19
• COMPOSITION FOR PREVENTING OR TREATING HAIR LOSS
  申请人：KYUNGPOOK NATIONAL UNIVERSITY INDUSTRY-ACADEMIC COOPERATION FOUNDATION

  公开号：US20210000793A1

  公开（公告）日：2021-01-07

  The present invention relates to a pharmaceutical composition for preventing or treating hair loss, a health functional food composition or a cosmetic composition, including a specific compound or a pharmaceutically acceptable salt thereof as an active ingredient, wherein the compound exhibits an excellent hair growth recovery effect in hair follicle tissues in which hair growth is inhibited without cytotoxicity, and thus hair loss can be more effectively prevented, improved, or treated.
• US8236963B2
  申请人：——

  公开号：US8236963B2

  公开（公告）日：2012-08-07