(1-phenyl-cyclopropyl)-(3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-pyrrolidin-1-yl)-methanone | 1151768-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1-phenyl-cyclopropyl)-(3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-pyrrolidin-1-yl)-methanone
• 英文别名: (1-phenylcyclopropyl)-[3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrrolidin-1-yl]methanone
• CAS: 1151768-69-2
• 化学式: C₂₁H₂₁N₃O
• 分子量: 331.417
• InChiKey: KONDYSYBNMOPRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3-dihydro-1H-pyrrole-1-carboxylate 在 盐酸 、 10% Pd(OH)2/C 、 甲酸铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 (1-phenyl-cyclopropyl)-(3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-pyrrolidin-1-yl)-methanone
  参考文献：
  名称：

  Structure-based design of 7-azaindole-pyrrolidine amides as inhibitors of 11β-hydroxysteroid dehydrogenase type I

  摘要：

  Indole-pyrrolidines were identified as inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) by high-throughput screening. Optimisation of the initial hit through structure-based design led to 7-azaindole-derivatives, with the best analogues displaying single digit nanomolar IC(50) potency. The modeling hypotheses were confirmed by solving the X-ray co-crystal structure of one of the lead compounds. These compounds were selective against 11β-hydroxysteroid dehydrogenase type 2 (selectivity ratio >200) and exhibited good inhibition of 11β-HSD1 (IC(50)<1μM) in a cellular model (3T3L1 adipocytes).

  DOI：

  10.1016/j.bmcl.2012.07.070

文献信息

• 7-Azaindole Derivatives as Selective 11-Beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitors
  申请人：Carniato Denis

  公开号：US20100267761A1

  公开（公告）日：2010-10-21

  The present invention relates to 7-azaindole derivatives of formula I as selective inhibitors of the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) and the use of such compounds for the treatment and prevention of metabolic syndrome, diabetes, insulin resistance, obesity, lipid disorders, glaucoma, osteoporosis, cognitive disorders, anxiety, depression, immune disorders, hypertension and other diseases and conditions.

  本发明涉及式I的7-氮杂吲哚衍生物，作为11-β-羟基类固醇脱氢酶1型(11β-HSD-1)的选择性抑制剂，以及这种化合物在代谢综合症、糖尿病、胰岛素抵抗、肥胖症、脂质紊乱、青光眼、骨质疏松症、认知障碍、焦虑、抑郁、免疫障碍、高血压和其他疾病和情况的治疗和预防中的使用。
• 7-AZAINDOLE DERIVATIVES AS SELECTIVE 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS
  申请人：Merck Patent GmbH

  公开号：EP2247589B1

  公开（公告）日：2012-11-21
• US8470849B2
  申请人：——

  公开号：US8470849B2

  公开（公告）日：2013-06-25
• Structure-based design of 7-azaindole-pyrrolidine amides as inhibitors of 11β-hydroxysteroid dehydrogenase type I
  作者：Eric Valeur、Serge Christmann-Franck、Franck Lepifre、Denis Carniato、Daniel Cravo、Christine Charon、Sophie Bozec、Djordje Musil、Per Hillertz、Liliane Doare、Fabien Schmidlin、Marc Lecomte、Melanie Schultz、Didier Roche

  DOI：10.1016/j.bmcl.2012.07.070

  日期：2012.9

  Indole-pyrrolidines were identified as inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) by high-throughput screening. Optimisation of the initial hit through structure-based design led to 7-azaindole-derivatives, with the best analogues displaying single digit nanomolar IC(50) potency. The modeling hypotheses were confirmed by solving the X-ray co-crystal structure of one of the lead compounds. These compounds were selective against 11β-hydroxysteroid dehydrogenase type 2 (selectivity ratio >200) and exhibited good inhibition of 11β-HSD1 (IC(50)<1μM) in a cellular model (3T3L1 adipocytes).