4-(5-(4-(2-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-ylcarbamoyl)-3-chloropyridin-2-yl)piperazine-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(5-(4-(2-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-ylcarbamoyl)-3-chloropyridin-2-yl)piperazine-2-carboxylic acid
• 英文别名: 4-(3-Chloro-5-(4-(2-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-ylcarbamoyl)pyridin-2-yl)piperazine-2-carboxylic acid；4-[3-chloro-5-[[4-[2-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]carbamoyl]pyridin-2-yl]piperazine-2-carboxylic acid
• 化学式: C₂₁H₁₆ClF₄N₅O₃S
• 分子量: 529.902
• InChiKey: MXODOOPIHHLFNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  136
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2-哌嗪羧酸盐酸盐 、 5.6-dichloro-N-(4-(2-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-yl)pyridine-3-carboxamide 生成 4-(5-(4-(2-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-ylcarbamoyl)-3-chloropyridin-2-yl)piperazine-2-carboxylic acid
  参考文献：
  名称：

  The identification of orally bioavailable thrombopoietin agonists

  摘要：

  Recently, we disclosed a series of potent pyrimidine benzamide-based thrombopoietin receptor agonists. Unfortunately, the structural features required for the desired activity conferred physicochemical properties that were not favorable for the development of an oral agent. The physical properties of the series were improved by replacing the aminopyrimidinyl group with a piperidine-4-carboxylic acid moiety. The resulting compounds possessed favorable in vivo pharmacokinetic properties, including good bioavailability. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.032

文献信息

• [EN] AMINOTHIAZOLE DERIVATIVES AS AGONISTS OF THE THROMBOPOIETIN RECEPTOR<br/>[FR] DÉRIVÉS D'AMINOTHIAZOLE SERVANT D'AGONISTES DU RÉCEPTEUR DE LA THROMBOPOÏÉTINE
  申请人：PFIZER PROD INC

  公开号：WO2007004038A1

  公开（公告）日：2007-01-11

  [EN] A compound of the formula (I) wherein R¹, R², R³, X, and d are defined as above. The presently disclosed compounds are TPO agonists useful as promoters of thrombopoiesis and megakaryocytopoiesis.
  [FR] L'invention concerne un composé de la formule (I) dans laquelle R¹, R², R³, X, et d sont définis tels qu'indiqués ci-dessus. Les composés présentés dans cette invention sont des agonistes de la TPO utiles comme promoteurs de la thrombopoïèse et de la mégacaryocytopoïèse.
• The identification of orally bioavailable thrombopoietin agonists
  作者：Michael J. Munchhof、Amy S. Antipas、Laura C. Blumberg、William H. Brissette、Matthew F. Brown、Jeffrey M. Casavant、Jonathan L. Doty、James Driscoll、Thomas M. Harris、Lilli A. Wolf-Gouveia、Christopher S. Jones、Qifang Li、Robert G. Linde、Paul D. Lira、Anthony Marfat、Eric McElroy、Mark Mitton-Fry、Sandra P. McCurdy、Lawrence A. Reiter、Sharon L. Ripp、Andrei Shavnya、Lisa M. Thomasco、Kristen A. Trevena

  DOI：10.1016/j.bmcl.2009.01.032

  日期：2009.3

  Recently, we disclosed a series of potent pyrimidine benzamide-based thrombopoietin receptor agonists. Unfortunately, the structural features required for the desired activity conferred physicochemical properties that were not favorable for the development of an oral agent. The physical properties of the series were improved by replacing the aminopyrimidinyl group with a piperidine-4-carboxylic acid moiety. The resulting compounds possessed favorable in vivo pharmacokinetic properties, including good bioavailability. (C) 2009 Elsevier Ltd. All rights reserved.