(S)-N-[trans-4-(4-cyanophenyl)cyclohexyl]-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-N-cyclopropylbenzamide | 917769-74-5

• 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: (S)-N-[trans-4-(4-cyanophenyl)cyclohexyl]-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-N-cyclopropylbenzamide
• CAS: 917769-74-5
• 化学式: C₂₆H₂₇F₃N₂O₂
• 分子量: 456.508
• InChiKey: XRRFWTVWZPSRQE-JTJYXVOQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.66
• 重原子数：
  33.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  64.33
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  (S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl) benzoic acid 、 trans-N-cyclopropyl-4-(4-cyano)phenylcyclohexylamine 在 碳酸氢钠 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以56%的产率得到(S)-N-[trans-4-(4-cyanophenyl)cyclohexyl]-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-N-cyclopropylbenzamide
  参考文献：
  名称：

  Discovery of Novel, Potent Benzamide Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Exhibiting Oral Activity in an Enzyme Inhibition ex Vivo Model^▽

  摘要：

  We report the discovery of potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1). The optimization and correlation of in vitro and in vivo metabolic stability will be described. Through modifications to our initial lead 2, we discovered pyridyl compound 13. This compound has a favorable pharmacokinetic profile across three species and showed a dose-dependent decrease in adipose 11beta-HSD1 activity in a monkey ex vivo pharmacodynamic model.

  DOI：

  10.1021/jm800310g

文献信息

• Benzamide derivatives and uses related thereto
  申请人：Powers P. Jay

  公开号：US20060293392A1

  公开（公告）日：2006-12-28

  Benzamide derivatives of formulae I and II, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof, and pharmaceutical compositions comprising the same, are described and have therapeutic utility, particularly in the treatment of diabetes, obesity, and related conditions and disorders: wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are defined as provided herein.

  公式I和II的苯甲酰胺衍生物，以及其药用可接受的盐、溶剂化合物、立体异构体和前药，以及包含它们的药物组合物被描述并具有治疗效用，特别是在糖尿病、肥胖和相关疾病和疾病的治疗中：其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11和R12如所述定义。
• BENZAMIDE DERIVATIVES AND USES RELATED THERETO
  申请人：POWERS Jay P.

  公开号：US20100069447A1

  公开（公告）日：2010-03-18

  Benzamide derivatives of formulae I and II, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof, and pharmaceutical compositions comprising the same, are described and have therapeutic utility, particularly in the treatment of diabetes, obesity, and related conditions and disorders: wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are defined as provided herein.

  本文介绍了公式I和II的苯甲酰胺衍生物，以及其药学上可接受的盐，溶剂化物，立体异构体和前药，以及包含它们的制药组合物，特别是在糖尿病，肥胖症和相关疾病和疾病的治疗中具有治疗效用：其中R1，R2，R3，R4，R5，R6，R7，R8，R9，R10，R11和R12如本文所述。
• US7605289B2
  申请人：——

  公开号：US7605289B2

  公开（公告）日：2009-10-20
• US8637576B2
  申请人：——

  公开号：US8637576B2

  公开（公告）日：2014-01-28
• Discovery of Novel, Potent Benzamide Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1) Exhibiting Oral Activity in an Enzyme Inhibition ex Vivo Model^▽
  作者：Lisa D. Julian、Zhulun Wang、Tracy Bostick、Seb Caille、Rebekah Choi、Michael DeGraffenreid、Yongmei Di、Xiao He、Randall W. Hungate、Juan C. Jaen、Jinsong Liu、Mario Monshouwer、Dustin McMinn、Yosup Rew、Athena Sudom、Daqing Sun、Hua Tu、Stefania Ursu、Nigel Walker、Xuelei Yan、Qiuping Ye、Jay P. Powers

  DOI：10.1021/jm800310g

  日期：2008.7

  We report the discovery of potent benzamide inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1). The optimization and correlation of in vitro and in vivo metabolic stability will be described. Through modifications to our initial lead 2, we discovered pyridyl compound 13. This compound has a favorable pharmacokinetic profile across three species and showed a dose-dependent decrease in adipose 11beta-HSD1 activity in a monkey ex vivo pharmacodynamic model.