(S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl) benzoic acid | 917771-46-1

• 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)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl) benzoic acid
• 英文别名: (S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzoic acid；4-[(2S)-1,1,1-trifluoro-2-hydroxypropan-2-yl]benzoic acid
• CAS: 917771-46-1
• 化学式: C₁₀H₉F₃O₃
• 分子量: 234.175
• InChiKey: BEPLLUQZLHVCMW-VIFPVBQESA-N

物化性质

• 沸点：
  347.5±42.0 °C(Predicted)
• 密度：
  1.410±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl) benzoic acid 在 吡啶 、 氯化亚砜 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzoic acid chloride
  参考文献：
  名称：

  Benzamide derivatives and uses related thereto

  摘要：

  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。

  公开号：

  US20060293392A1
• 作为产物：
  描述：

  4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzonitrile 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以5.45 g的产率得到(S)-4-(1,1,1-trifluoro-2-hydroxypropan-2-yl) benzoic acid
  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

• Synthesis, in Vitro Covalent Binding Evaluation, and Metabolism of ¹⁴C-Labeled Inhibitors of 11β-HSD1
  作者：Daqing Sun、Qiuping Ye、Xuelei Yan、Yosup Rew、Peter Fan、Xiao He、Min Jiang、Dustin L. McMinn、Mario Monshouwer、Hua Tu、Jay P. Powers

  DOI：10.1021/ml500331y

  日期：2014.11.13

  In this letter, we reported the design and synthesis of three potent, selective, and orally bioavailable 11β-HSD1 inhibitors labeled with 14C: AMG 456 (1), AM-6949 (2), and AM-7715 (3). We evaluated the covalent protein binding of the labeled inhibitors in human liver microsomes in vitro and assessed their potential bioactivation risk in humans. We then studied the in vitro mechanism of 2 in human

  在这封信中，我们报道了标记为14 C的三种有效，选择性和口服生物利用的11β-HSD1抑制剂的设计和合成：AMG 456（1），AM-6949（2）和AM-7715（3）。我们评估了人类肝微粒体中标记的抑制剂的共价蛋白结合，并评估了其在人体中潜在的生物激活风险。然后，我们研究了人类肝细胞中2的体外机制以及反应性中间体的形成。我们的研究结果表明1和3具有较低的人类代谢生物激活潜力，而2具有较高的风险。
• 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。
• Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors
  作者：Daqing Sun、Zhulun Wang、Seb Caille、Michael DeGraffenreid、Felix Gonzalez-Lopez de Turiso、Randall Hungate、Juan C. Jaen、Ben Jiang、Lisa D. Julian、Ron Kelly、Dustin L. McMinn、Jacob Kaizerman、Yosup Rew、Athena Sudom、Hua Tu、Stefania Ursu、Nigel Walker、Maren Willcockson、Xuelei Yan、Qiuping Ye、Jay P. Powers

  DOI：10.1016/j.bmcl.2010.10.129

  日期：2011.1

  The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11 beta-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models. (c) 2010 Elsevier Ltd. All rights reserved.
• Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11β-HSD1 inhibitors
  作者：Yosup Rew、Dustin L. McMinn、Zhulun Wang、Xiao He、Randall W. Hungate、Juan C. Jaen、Athena Sudom、Daqing Sun、Hua Tu、Stefania Ursu、Elisia Villemure、Nigel P.C. Walker、Xuelei Yan、Qiuping Ye、Jay P. Powers

  DOI：10.1016/j.bmcl.2009.01.058

  日期：2009.3

  Discovery and optimization of a piperidyl benzamide series of 11beta-HSD1 inhibitors is described. This series was derived from a cyclohexyl benzamide lead structures to address PXR selectivity, high non-specific protein binding, poor solubility, limited in vivo exposure, and in vitro cytotoxicity issues observed with the cyclohexyl benzamide structures. These efforts led to the discovery of piperidyl benzamide 15 which features improved properties over the cyclohexyl benzamide derivatives.
• Optimization of novel di-substituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors
  作者：Dustin L. McMinn、Yosup Rew、Athena Sudom、Seb Caille、Michael DeGraffenreid、Xiao He、Randall Hungate、Ben Jiang、Juan Jaen、Lisa D. Julian、Jacob Kaizerman、Perry Novak、Daqing Sun、Hua Tu、Stefania Ursu、Nigel P.C. Walker、Xuelei Yan、Qiuping Ye、Zhulun Wang、Jay P. Powers

  DOI：10.1016/j.bmcl.2009.01.026

  日期：2009.3

  Novel 4,4-disubstituted cyclohexylbenzamide inhibitors of 11beta-HSD1 were optimized to account for liabilities relating to in vitro pharmacokinetics, cytotoxicity and protein-related shifts in potency. A representative compound showing favorable in vivo pharmacokinetics was found to be an efficacious inhibitor of 11beta-HSD1 in a rat pharmacodynamic model (ED(50)=10mg/kg).