{trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)phenyl]cyclohexyl}acetic acid | 1236361-44-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: {trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)phenyl]cyclohexyl}acetic acid
• CAS: 1236361-44-6
• 化学式: C₂₁H₂₄N₄O₃
• 分子量: 380.447
• InChiKey: DVHSQIPHRVBFFO-HDJSIYSDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  28.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  109.41
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  methyl {trans-4-[4-(5-cyano-4-methoxy-6-oxo-3,6-dihydropyridin-1(2H)-yl)phenyl]cyclohexyl}acetate 在 20 % Pd(OH)2/C 、 氢气 、 sodium hydride 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 25.0~100.0 ℃ 、5.52 MPa 条件下， 生成 {trans-4-[4-(4-amino-5-oxo-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)phenyl]cyclohexyl}acetic acid
  参考文献：
  名称：

  Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1

  摘要：

  Acyl-CoA:diacylglycerol acyltransferase-1 (DGAT-1) catalyzes the final committed step in the biosynthesis of triglycerides. DGAT-1 knockout mice have been shown to be resistant to diet-induced obesity and have increased insulin sensitivity. Thus, inhibition of DGAT-1 may represent an attractive target for the treatment of obesity or type II diabetes. Herein, we report the discovery and characterization of a potent and selective DGAT-1 inhibit or PF-04620110 (3). Compound 3 inhibits DGAT-1 with an IC50 of 19 nM and shows high selectivity versus a broad panel of off-target pharmacologic end points. In vivo DGAT-1 inhibition has been demonstrated through reduction of plasma triglyceride levels in rodents at doses of >= 0.1 mg/kg following a lipid challenge. On the basis of this pharmacologic and pharmacokinetic profile, compound 3 has been advanced to human clinical studies.

  DOI：

  10.1021/ml200051p

文献信息

• 4-AMINO-7,8-DIHYDROPYRIDO[4,3-d]PYRIMIDIN-5(6H)-ONE DERIVATIVES
  申请人：Dow Robert L.

  公开号：US20100197590A1

  公开（公告）日：2010-08-05

  The invention provides compounds of Formula (Ia) or pharmaceutically acceptable salts thereof, as well as the preparation, compositions and uses thereof, where R 1 , R 2 , R 3 , and m are defined as described above.

  该发明提供了式(Ia)的化合物或其药用可接受的盐，以及其制备、组成和用途，其中R1、R2、R3和m的定义如上所述。
• [EN] 4-AMINO-7,8-DIHYDROPYRIDO[4,3-D]PYRIMIDIN-5(6H)-ONE DERIVATIVES<br/>[FR] DÉRIVÉS DE 4-AMINO-7,8-DIHYDROPYRIDO[4,3-D]PYRIMIDIN-5(6H)-ONE
  申请人：PFIZER

  公开号：WO2010089685A1

  公开（公告）日：2010-08-12

  The invention provides compounds of Formula (Ia) or pharmaceutically acceptable salts thereof, as well as the preparation, compositions and uses thereof, where R1, R2, R3, and m are defined as described above.
• Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1
  作者：Robert L. Dow、Jian-Cheng Li、Michael P. Pence、E. Michael Gibbs、Jennifer L. LaPerle、John Litchfield、David W. Piotrowski、Michael J. Munchhof、Tara B. Manion、William J. Zavadoski、Gregory S. Walker、R. Kirk McPherson、Susan Tapley、Eliot Sugarman、Angel Guzman-Perez、Paul DaSilva-Jardine

  DOI：10.1021/ml200051p

  日期：2011.5.12

  Acyl-CoA:diacylglycerol acyltransferase-1 (DGAT-1) catalyzes the final committed step in the biosynthesis of triglycerides. DGAT-1 knockout mice have been shown to be resistant to diet-induced obesity and have increased insulin sensitivity. Thus, inhibition of DGAT-1 may represent an attractive target for the treatment of obesity or type II diabetes. Herein, we report the discovery and characterization of a potent and selective DGAT-1 inhibit or PF-04620110 (3). Compound 3 inhibits DGAT-1 with an IC50 of 19 nM and shows high selectivity versus a broad panel of off-target pharmacologic end points. In vivo DGAT-1 inhibition has been demonstrated through reduction of plasma triglyceride levels in rodents at doses of >= 0.1 mg/kg following a lipid challenge. On the basis of this pharmacologic and pharmacokinetic profile, compound 3 has been advanced to human clinical studies.