tert-butyl 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3-dihydro-1H-pyrrole-1-carboxylate | 1209463-26-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: tert-butyl 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3-dihydro-1H-pyrrole-1-carboxylate
• 英文别名: tert-butyl 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3-dihydropyrrole-1-carboxylate
• CAS: 1209463-26-2
• 化学式: C₁₆H₁₉N₃O₂
• 分子量: 285.346
• InChiKey: RDCOQGBOWACUHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  7-氮杂吲哚 、 1-叔丁氧碳基-3-吡咯烷酮 在 potassium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 生成 tert-butyl 3-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,5-dihydro-1H-pyrrole-1-carboxylate 、 tert-butyl 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3-dihydro-1H-pyrrole-1-carboxylate
  参考文献：
  名称：

  [EN] FUSED PYRROLIDINO-CYCLOPROPANE DERIVATIVES AS SELECTIVE 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS
  [FR] DÉRIVÉS DE LA FUSION PYRROLIDINO-CYCLOPROPANE UTILISÉS COMME INHIBITEURS SÉLECTIFS DE LA 11-BÊTA-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1

  摘要：

  本发明涉及式（I）至（II）的融合吡咯烷基环丙烷衍生物，作为选择性抑制剂11-β-羟基类固醇脱氢酶1型（11-β-HSD-1）的酶以及这些化合物在代谢综合征、糖尿病、胰岛素抵抗、肥胖症、脂质异常、青光眼、骨质疏松/认知障碍、焦虑、抑郁、免疫障碍、高血压和其他疾病和病况的治疗和/或预防的用途。

  公开号：

  WO2010022850A1

文献信息

• [EN] FUSED PYRROLIDINO-CYCLOPROPANE DERIVATIVES AS SELECTIVE 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS<br/>[FR] DÉRIVÉS DE LA FUSION PYRROLIDINO-CYCLOPROPANE UTILISÉS COMME INHIBITEURS SÉLECTIFS DE LA 11-BÊTA-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1
  申请人：MERCK PATENT GMBH

  公开号：WO2010022850A1

  公开（公告）日：2010-03-04

  The present invention relates to fused pyrrolidino-cyclopropane derivatives according to Formulae (I) to (II), as selective inhibitors of the enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11-β-HSD-1 ) and the use of such compounds for the treatment and/or 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）至（II）的融合吡咯烷基环丙烷衍生物，作为选择性抑制剂11-β-羟基类固醇脱氢酶1型（11-β-HSD-1）的酶以及这些化合物在代谢综合征、糖尿病、胰岛素抵抗、肥胖症、脂质异常、青光眼、骨质疏松/认知障碍、焦虑、抑郁、免疫障碍、高血压和其他疾病和病况的治疗和/或预防的用途。
• Fused pyrrolidino-cyclopropane derivatives as selective 11-beta-hydroxysteroid dehydrogenase type 1 inhibitors
  申请人：Valeur Eric

  公开号：US20110172265A1

  公开（公告）日：2011-07-14

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

  本发明涉及公式（I）至（IV）的融合吡咯啉基环丙烷衍生物，作为选择性抑制剂11-β-羟基类固醇脱氢酶1（11-β-HSD-1）的酶，并且利用这种化合物用于治疗和/或预防代谢综合征、糖尿病、胰岛素抵抗、肥胖症、脂质代谢异常、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病况。
• FUSED PYRROLIDINO-CYCLOPROPANE DERIVATIVES AS SELECTIVE 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1 INHIBITORS
  申请人：Merck Patent GmbH

  公开号：EP2321317A1

  公开（公告）日：2011-05-18
• US8486964B2
  申请人：——

  公开号：US8486964B2

  公开（公告）日：2013-07-16
• 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).