methyl {trans-4-[4-(5-cyano-4-methoxy-6-oxo-3,6-dihydropyridin-1(2H)-yl)phenyl]cyclohexyl}acetate | 1236361-48-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: methyl {trans-4-[4-(5-cyano-4-methoxy-6-oxo-3,6-dihydropyridin-1(2H)-yl)phenyl]cyclohexyl}acetate
• CAS: 1236361-48-0
• 化学式: C₂₂H₂₆N₂O₄
• 分子量: 382.459
• InChiKey: JNDDAGAUYMXYIV-WKILWMFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.68
• 重原子数：
  28.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  79.63
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  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 作用下， 以 1,4-二氧六环 为溶剂， 25.0~100.0 ℃ 、5.52 MPa 条件下， 生成 methyl 2-((1r,4r)-4-(4-(4-amino-5-oxo-7,8-dihydropyrido[4,3-d]pyrimidin-6(5H)-yl)phenyl)cyclohexyl)acetate
  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
• 作为产物：
  描述：

  (trans)-methyl 2-(4-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)cyclohexyl)acetate 在 草酰氯 、 palladium diacetate 、 caesium carbonate 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 N,N-二甲基甲酰胺 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 methyl {trans-4-[4-(5-cyano-4-methoxy-6-oxo-3,6-dihydropyridin-1(2H)-yl)phenyl]cyclohexyl}acetate
  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.