(2S)-(acetylthio)(cyclohexyl)ethanoic acid | 929003-26-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2S)-(acetylthio)(cyclohexyl)ethanoic acid
• 英文别名: (S)-2-acetylthio-2-cyclohexylacetic acid；(2S)-2-acetylsulfanyl-2-cyclohexylacetic acid
• CAS: 929003-26-9
• 化学式: C₁₀H₁₆O₃S
• 分子量: 216.301
• InChiKey: PTYWGCDOWDHSRM-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-(acetylthio)(cyclohexyl)ethanoic acid 在 lithium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S,5S)-5-((S)-2-Cyclohexyl-2-mercapto-acetylamino)-4-oxo-1,2,4,5,6,7-hexahydro-azepino[3,2,1-hi]indole-2-carboxylic acid
  参考文献：
  名称：

  Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase by tricyclic benzazepinone thiols

  摘要：

  Various thioacyl analogs of CGS 28106, a tricyclic dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase, have been synthesized and their inhibitory potencies evaluated in vitro. The structure-activity relationship supports the proposed hypothesis that, despite its conformational constraints, CGS 28106 can inhibit the two distinct metalloproteases by adopting different binding modes. Tn addition, the structural features of CGS 28106 confer remarkable oral activity to this dual inhibitor, as measured by its ability to block the angiotensin-I presser response and to potentiate plasma levels of atrial natriuretic peptide. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00529-x
• 作为产物：
  描述：

  (R)-2-bromo-2-cyclohexylacetic acid 、 potassium thioacetate 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (2S)-(acetylthio)(cyclohexyl)ethanoic acid
  参考文献：
  名称：

  Thio-containing inhibitors of aminopeptidase P, compositions thereof and method of use

  摘要：

  本发明涉及一种含α硫基的化合物，能够抑制酶、膜氨肽酶P（mAPP或APP），其天然底物为激肽。该化合物可用作药物代理，因为通过抑制激肽降解，使激肽能够在心血管系统上发挥其有益作用，改善肾功能，并改善葡萄糖耐量和胰岛素敏感性。本发明还涉及一种含有本发明mAPP抑制剂和药用可接受载体的药物组合物。另一方面，本发明涉及一种在需要治疗的哺乳动物患者，优选为人类，中抑制激肽降解的方法，包括向患者投予本发明的α硫基化合物的治疗有效量。本发明的方法还包括向需要治疗的哺乳动物患者投予抑制肾素转化酶（ACE）的治疗有效量的进一步步骤。

  公开号：

  US20070060525A1

文献信息

• THIO-CONTAINING INHIBITORS OF AMINOPEPTIDASE P, COMPOSITIONS THEREOF AND METHOD OF USE
  申请人：Simmons, William H.

  公开号：EP1924275B1

  公开（公告）日：2012-08-08
• EP1924275A4
  申请人：——

  公开号：EP1924275A4

  公开（公告）日：2009-07-29
• US7390789B2
  申请人：——

  公开号：US7390789B2

  公开（公告）日：2008-06-24
• [EN] THIO-CONTAINING INHIBITORS OF AMINOPEPTIDASE P, COMPOSITIONS THEREOF AND METHOD OF USE<br/>[FR] INHIBITEURS CONTENANT UN COMPOSE THIO D'UNE AMINOPEPTIDASE P, LEURS COMPOSITIONS ET PROCEDE D'UTILISATION ASSOCIES
  申请人：SIMMONS WILLIAM H

  公开号：WO2007032887A2

  公开（公告）日：2007-03-22

  [EN] The present invention is directed to an a thio-containing compound that is capable of inhibiting the enzyme, membrane aminopeptidase P (mAPP or APP), whose natural substrate is bradykinin. The compound is useful as a pharmaceutical agent because by inhibiting bradykinin degradation, the compound allows bradykinin to exert its beneficial effects on the cardiovascular system, to improve renal function, and to improve glucose tolerance and insulin-sensitivity. The present invention is also directed to a pharmaceutical composition comprising the mAPP inhibitor of the present invention and a pharmaceutically acceptable carrier. In another aspect, the present invention is directed to a method of inhibiting bradykinin degradation in a mammalian patient, preferably human, in need of treatment comprising administering to the patient a therapeutically effective amount of an a thio-containing compound of the present invention. The method of the present invention also contemplates the further step of administering to the mammalian patient in need of treatment a therapeutically effective amount of an inhibitor of angiotensin converting enzyme (ACE).
  [FR] L'invention concerne un composé contenant thio capable d'inhiber l'enzyme, la membrane aminopeptidase P (mAPP, ou APP), dont le substrat naturel est la bradykinine. Le composé est utilisé en tant qu'agent pharmaceutique grâce à l'inhibition de la dégradation de la bradykinine, le composé permettant à la bradykinine d'exercer ses effets bénéfiques sur le système cardiovasculaire, d'améliorer les fonctions rénales et d'améliorer la tolérance au glucose et la sensibilité à l'insuline. L'invention concerne également une composition pharmaceutique comprenant un inhibiteur de mAPP et une porteuse pharmaceutiquement acceptable. Selon un autre aspect de l'invention, un procédé permet d'inhiber la dégradation de la bradykinine chez un patient mammifère, de préférence un humain, nécessitant un traitement comprenant l'administration d'une quantité thérapeutique efficace d'un composé comprenant thio. Le procédé comprend également l'administration au patient d'une quantité efficace d'un inhibiteur de l'enzyme de conversion de l'angiotensine (ACE).
• Dual inhibition of angiotensin-converting enzyme and neutral endopeptidase by tricyclic benzazepinone thiols
  作者：Stéphane De Lombaert、Louis Blanchard、Lisa B. Stamford、Yumi Sakane、Carol Berry、Rajendra D. Ghai、Angelo J. Trapani

  DOI：10.1016/s0960-894x(96)00529-x

  日期：1996.12

  Various thioacyl analogs of CGS 28106, a tricyclic dual inhibitor of angiotensin-converting enzyme and neutral endopeptidase, have been synthesized and their inhibitory potencies evaluated in vitro. The structure-activity relationship supports the proposed hypothesis that, despite its conformational constraints, CGS 28106 can inhibit the two distinct metalloproteases by adopting different binding modes. Tn addition, the structural features of CGS 28106 confer remarkable oral activity to this dual inhibitor, as measured by its ability to block the angiotensin-I presser response and to potentiate plasma levels of atrial natriuretic peptide. Copyright (C) 1996 Elsevier Science Ltd