(1R,2R)-2-({4'-[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid | 959122-05-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1R,2R)-2-({4'-[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid
• 英文别名: (1R,2R)-2-({4-[4-({[4-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]phenyl}carbonyl)cyclopentane-1-carboxylic acid；(1R,2R)-2-[4-[4-[[4-(trifluoromethyl)phenyl]carbamoylamino]phenyl]benzoyl]cyclopentane-1-carboxylic acid
• CAS: 959122-05-5
• 化学式: C₂₇H₂₃F₃N₂O₄
• 分子量: 496.486
• InChiKey: HCWAEJBFWIPTDG-DHIUTWEWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  95.5
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-({4'-[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid 在 sodium tetrahydroborate 、 盐酸 、 甲醇 、 水 作用下， 以 甲醇 为溶剂， 生成 (1R,2R)-2-((S)-hydroxy{4'-[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]-1,1'-biphenyl-4-yl}methyl)cyclopentanecarboxylic acid 、 (1R,2R)-2-((R)-hydroxy{4'-[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]-1,1'-biphenyl-4-yl}methyl)cyclopentanecarboxylic acid
  参考文献：
  名称：

  Inhibitors of diacylglycerol O-acyltransferase type 1 enzyme

  摘要：

  本发明涉及式(I)的化合物。其中R1、R2、R3、R4、R5、R6、m、n、p和q在此处定义。还公开了用于治疗DGAT-1相关疾病或症状的药物组合物和方法。

  公开号：

  US20080015227A1
• 作为产物：
  描述：

  (1R,2R)-2-({4'-[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid methyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 (1R,2R)-2-({4'-[({[4-(trifluoromethyl)phenyl]amino}carbonyl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid
  参考文献：
  名称：

  Validation of Diacyl Glycerolacyltransferase I as a Novel Target for the Treatment of Obesity and Dyslipidemia Using a Potent and Selective Small Molecule Inhibitor

  摘要：

  A highly potent and selective DGAT-1 inhibitor was identified and used in rodent models of obesity and postprandial chylomicron excursion to validate DGAT-1 inhibition as a novel approach for the treatment of metabolic diseases. Specifically, compound 4a conferred weight loss and a reduction in liver triglycerides when dosed chronically in DIO mice and depleted serum triglycerides following a lipid challenge in a dose-dependent manner, thus, reproducing major phenotypical characteristics of DGAT-1(-/-) mice.

  DOI：

  10.1021/jm7013887

文献信息

• [EN] INHIBITORS OF DIACYLGLYCEROL O-ACYLTRANSFERASE TYPE 1 ENZYME<br/>[FR] INHIBITEURS DE L'ENZYME DIACYLGLYCÉROL O-ACYLTRANSFÉRASE DE TYPE 1
  申请人：ABBOTT LAB

  公开号：WO2007137103A2

  公开（公告）日：2007-11-29

  [EN] The present invention relates to compounds of formula (I) wherein R¹, R², R³, R⁴, R⁵, R⁶, m, n, p and q are defined herein. Pharmaceutical compositions and methods for treating DGAT-1 related diseases or conditions are also disclosed.
  [FR] La présente invention concerne des composés de formule (I), dans laquelle R¹, R², R³, R⁴, R⁵, R⁶, m, n, p et q sont tels que définis dans le mémorandum descriptif. Elle concerne également des compositions pharmaceutiques et des méthodes de traitement de maladies ou affections associées à DGAT-1.
• Inhibitors of diacylglycerol O-acyltransferase type 1 enzyme
  申请人：Kym R. Philip

  公开号：US20080015227A1

  公开（公告）日：2008-01-17

  The present invention relates to compounds of formula (I). wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , m, n, p and q are defined herein Pharmaceutical compositions and methods for treating DGAT-1 related diseases or conditions are also disclosed.

  本发明涉及式(I)的化合物。其中R1、R2、R3、R4、R5、R6、m、n、p和q在此处定义。还公开了用于治疗DGAT-1相关疾病或症状的药物组合物和方法。
• Validation of Diacyl Glycerolacyltransferase I as a Novel Target for the Treatment of Obesity and Dyslipidemia Using a Potent and Selective Small Molecule Inhibitor
  作者：Gang Zhao、Andrew J. Souers、Martin Voorbach、H. Doug Falls、Brian Droz、Sevan Brodjian、Yau Yi Lau、Rajesh R. Iyengar、Ju Gao、Andrew S. Judd、Seble H. Wagaw、Matthew M. Ravn、Kenneth M. Engstrom、John K. Lynch、Mathew M. Mulhern、Jennifer Freeman、Brian D. Dayton、Xiaojun Wang、Nelson Grihalde、Dennis Fry、David W. A. Beno、Kennan C. Marsh、Zhi Su、Gilbert J. Diaz、Christine A. Collins、Hing Sham、Regina M. Reilly、Michael E. Brune、Philip R. Kym

  DOI：10.1021/jm7013887

  日期：2008.2.1

  A highly potent and selective DGAT-1 inhibitor was identified and used in rodent models of obesity and postprandial chylomicron excursion to validate DGAT-1 inhibition as a novel approach for the treatment of metabolic diseases. Specifically, compound 4a conferred weight loss and a reduction in liver triglycerides when dosed chronically in DIO mice and depleted serum triglycerides following a lipid challenge in a dose-dependent manner, thus, reproducing major phenotypical characteristics of DGAT-1(-/-) mice.