4-Amino-2-(4-chloro-phenyl)-thiazole-5-carboxylic acid methyl ester | 515141-56-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-Amino-2-(4-chloro-phenyl)-thiazole-5-carboxylic acid methyl ester
• 英文别名: Methyl 4-amino-2-(4-chlorophenyl)-1,3-thiazole-5-carboxylate
• CAS: 515141-56-7
• 化学式: C₁₁H₉ClN₂O₂S
• 分子量: 268.724
• InChiKey: QJZWJXHEFMMBHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-Amino-2-(4-chloro-phenyl)-thiazole-5-carboxylic acid methyl ester 以 乙醇 为溶剂， 反应 21.0h， 生成 2-(4-Chloro-phenyl)-6-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-6H-thiazolo[4,5-d]pyrimidin-7-one
  参考文献：
  名称：

  The discovery and optimization of pyrimidinone-containing MCH R1 antagonists

  摘要：

  Optimization of a series of constrained melanin-concentrating hormone receptor 1 (MCH RI) antagonists has provided compounds with potent and selective MCH R1 activity. Details of the optimization process are provided and the use of one of the compounds in an animal model of diet-induced obesity is presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.008
• 作为产物：
  描述：

  methyl 4-chlorobenzenecarbodithioate 在 potassium methanolate 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 4-Amino-2-(4-chloro-phenyl)-thiazole-5-carboxylic acid methyl ester
  参考文献：
  名称：

  The discovery and optimization of pyrimidinone-containing MCH R1 antagonists

  摘要：

  Optimization of a series of constrained melanin-concentrating hormone receptor 1 (MCH RI) antagonists has provided compounds with potent and selective MCH R1 activity. Details of the optimization process are provided and the use of one of the compounds in an animal model of diet-induced obesity is presented. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.07.008

文献信息

• Identification of pyrazolo-pyrimidinones as GHS-R1a antagonists and inverse agonists for the treatment of obesity
  作者：William McCoull、Peter Barton、Anders Broo、Alastair J. H. Brown、David S. Clarke、Gareth Coope、Robert D. M. Davies、Alexander G. Dossetter、Elizabeth E. Kelly、Laurent Knerr、Philip MacFaul、Jane L. Holmes、Nathaniel Martin、Jane E. Moore、David Morgan、Claire Newton、Krister Österlund、Graeme R. Robb、Eleanor Rosevere、Nidhal Selmi、Stephen Stokes、Tor S. Svensson、Victoria B. K. Ullah、Emma J. Williams

  DOI：10.1039/c2md20340e

  日期：——

  A pyrazolo-pyrimidinone based series of growth hormone secretagogue receptor type 1a (GHS-R1a) antagonists and inverse agonists were identified using a scaffold hop from known quinazolinone GHS-R1a modulators. Lipophilicity was reduced to decrease hERG activity while maintaining GHS-R1a affinity. SAR exploration of a piperidine substituent was used to identify small cyclic groups as a functional switch from partial agonists to neutral antagonists and inverse agonists. A tool compound was identified which had good overall properties and sufficient oral plasma and CNS exposure to demonstrate reduced food intake in mice through a mechanism involving GHS-R1a.

  研究人员利用已知喹唑啉酮类 GHS-R1a 调节剂的支架，鉴定了一系列基于吡唑并嘧啶酮的生长激素分泌受体 1a 型（GHS-R1a）拮抗剂和反向激动剂。在保持 GHS-R1a 亲和力的同时，降低了亲脂性以降低 hERG 活性。利用对哌啶取代基的 SAR 探索，确定了从部分激动剂到中性拮抗剂和反向激动剂的功能转换小环状基团。最终确定了一种工具化合物，该化合物具有良好的整体特性和足够的口服血浆和中枢神经系统暴露量，可通过涉及 GHS-R1a 的机制证明小鼠的食物摄入量降低。
• [EN] PYRIMIDINONES AS MELANIN CONCENTRATING HORMONE RECEPTOR 1<br/>[FR] PYRIMIDINONES EN TANT QUE RECEPTEUR 1 DE L'HORMONE DE CONCENTRATION DE LA MELANINE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO2003033476A1

  公开（公告）日：2003-04-24

  A compound of formula (Ia) comprising a pharmaceutically acceptable salt or solvate thereof, formulations, processes of preparing, and methods of administering to mammals are provided

  本发明提供了化合物(Ia)的配方，包括其药物可接受的盐或溶剂，制备过程和哺乳动物的给药方法。
• Pyrimidinones as melanin concentrating hormone receptor 1
  申请人：——

  公开号：US20040220404A1

  公开（公告）日：2004-11-04

  A compound of formula (Ia) comprising a pharmaceutically acceptable salt or solvate thereof, formulations, processes of preparing, and methods of administering to mammals are provided 1

  提供了一种化合物(Ia)的配方，包括其药用可接受的盐或溶剂，制备过程以及对哺乳动物的给药方法。
• PYRIMIDINONES AS MELANIN CONCENTRATING HORMONE RECEPTOR 1
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1442025B1

  公开（公告）日：2007-03-07
• US7285557B2
  申请人：——

  公开号：US7285557B2

  公开（公告）日：2007-10-23