iso-propyl 2-cyano-6-(3,4-difluorobenzoyl)-4,4-dimethyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-d]azepine-8-carboxylate | 1155659-12-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - Pyrroloazepines
• 英文名称: iso-propyl 2-cyano-6-(3,4-difluorobenzoyl)-4,4-dimethyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-d]azepine-8-carboxylate
• 英文别名: Isopropyl 2-cyano-6-(3,4-difluorobenzoyl)-4,4-dimethyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-d]azepine-8-carboxylate；propan-2-yl 2-cyano-6-(3,4-difluorobenzoyl)-4,4-dimethyl-1,5,7,8-tetrahydropyrrolo[2,3-d]azepine-8-carboxylate
• CAS: 1155659-12-3
• 化学式: C₂₂H₂₃F₂N₃O₃
• 分子量: 415.44
• InChiKey: JTWLRQHGXNKRJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 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：
  86.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  iso-propyl 2-cyano-4,4-dimethyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-d]azepine-8-carboxylate 、 3,4-二氟苯甲酰氯 生成 iso-propyl 2-cyano-6-(3,4-difluorobenzoyl)-4,4-dimethyl-1,4,5,6,7,8-hexahydropyrrolo[2,3-d]azepine-8-carboxylate
  参考文献：
  名称：

  1,4,5,6,7,8-HEXAHYDRO -PYRROLO[2,3-d]AZEPINES AND -IMIDAZO[4,5-d]AZEPINES AS MODULATORS OF NUCLEAR RECEPTOR ACTIVITY

  摘要：

  本发明涉及化合物I式的化学实体及其药学上可接受的盐，其中X选择自CN、CF3、CF2H、S（O）nR6和S（O）2N（R9）R10; Y选择自CR11和N; Z选择自O和NH; R3选择自—C（O）R12和—C（O）N（R9）R10; n，R1，R2和R4-R12在此定义；包含一种或多种此类化学实体的组合物；以及使用一种或多种此类化学实体调节某些受体（例如，法尼索X）的活性或治疗或预防与这些受体活性相关的一种或多种疾病或疾病症状的方法。

  公开号：

  US20090131409A1

文献信息

• 1,4,5,6,7,8-HEXAHYDRO -PYRROLO[2,3-d]AZEPINES AND -IMIDAZO[4,5-d]AZEPINES AS MODULATORS OF NUCLEAR RECEPTOR ACTIVITY
  申请人：Mehlmann John Francis

  公开号：US20090131409A1

  公开（公告）日：2009-05-21

  Disclosed are chemical entities including compounds of Formula I and pharmaceutically acceptable salts thereof, wherein X is chosen from CN, CF 3 , CF 2 H, S(O) n R 6 , and S(O) 2 N(R 9 )R 10 ; Y is chosen from CR 11 and N; Z is chosen from O and NH; R 3 is chosen from —C(O)R 12 and —C(O)N(R 9 )R 10 ; and n, R 1 , R 2 and R 4 -R 12 are defined herein; compositions comprising one or more such chemical entities; and methods of using one or more such chemical entities for modulating the activity of certain receptors (e.g., farnesoid X) or for the treatment or prevention of one or more symptoms of disease or disorder related to the activity of those receptors.

  本发明涉及化合物I式及其药学上可接受的盐，其中X选择自CN、CF3、CF2H、S(O)nR6和S(O)2N(R9)R10；Y选择自CR11和N；Z选择自O和NH；R3选择自—C(O)R12和—C(O)N(R9)R10；并且在此定义中n、R1、R2和R4-R12；包含一种或多种此类化学实体的组合物；以及使用一种或多种此类化学实体来调节某些受体（例如farnesoid X）的活性或治疗或预防与这些受体活性相关的一种或多种疾病或症状的方法。
• Pyrrole[2,3-d]azepino compounds as agonists of the farnesoid X receptor (FXR)
  作者：John F. Mehlmann、Matthew L. Crawley、Joseph T. Lundquist、Ray J. Unwalla、Douglas C. Harnish、Mark J. Evans、Callain Y. Kim、Jay E. Wrobel、Paige E. Mahaney

  DOI：10.1016/j.bmcl.2009.07.148

  日期：2009.9

  Pyrrole[2,3-d]azepines have been identified as potent agonists of the farnesoid X receptor (FXR). Based on the planar X-ray crystal structure of WAY-362450 1 in the ligand binding domain and molecular modeling studies, non-planar reduced compounds were designed which led to agonists that exhibit high aqueous solubility and retain moderate in vitro potency. (C) 2009 Elsevier Ltd. All rights reserved.