(3R,4S)-4-Amino-5-cyclohexyl-2,2-difluoro-3-hydroxy-pentanoic acid ethyl ester; hydrochloride | 112526-44-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3R,4S)-4-Amino-5-cyclohexyl-2,2-difluoro-3-hydroxy-pentanoic acid ethyl ester; hydrochloride
• 英文别名: ethyl (3R,4S)-4-amino-5-cyclohexyl-2,2-difluoro-3-hydroxypentanoate;hydrochloride
• CAS: 112526-44-0
• 化学式: C₁₃H₂₃F₂NO₃*ClH
• 分子量: 315.788
• InChiKey: FZHJQODSNQTZKM-VZXYPILPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.27
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  72.6
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3R,4S)-4-Amino-5-cyclohexyl-2,2-difluoro-3-hydroxy-pentanoic acid ethyl ester; hydrochloride 在 盐酸 、 二氯乙酸 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 (S)-5-Cyclohexyl-2,2-difluoro-4-{(S)-2-[(S)-2-(morpholine-4-sulfonylamino)-3-phenyl-propionylamino]-3-[2-(2,2,2-trichloro-ethoxycarbonylamino)-thiazol-4-yl]-propionylamino}-3-oxo-pentanoic acid ethyl ester
  参考文献：
  名称：

  Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors

  摘要：

  A series of renin inhibitors was synthesized that contained a 2-amino-4-thiazolyl moiety at the P2 position. These derivatives are potent inhibitors of monkey renin in vitro and are selective in that they only weakly inhibit the closely related aspartic proteinase, bovine cathepsin D. Four compounds exhibited oral blood pressure lowering activity in high-renin normotensive monkeys. One of these compounds, 22 (PD 134672), was selected for further evaluation in renal hypertensive monkeys, on the basis of its superior efficacy and duration of action in the in vitro assays and the normotensive primate model.

  DOI：

  10.1021/jm00092a006

文献信息

• Difluorocyclostatine containing polypeptides
  申请人：PFIZER INC.

  公开号：EP0222523A2

  公开（公告）日：1987-05-20

  Polypeptides and derivatives thereof containing 2,2-difluorocyclostatine are useful for inhibiting the angiotensinogen-cleaving action of the enzyme renin.

  含有 2,2-二氟环司他丁的多肽及其衍生物可用于抑制肾素酶的血管紧张素原分解作用。
• [EN] DIFLUOROCYCLOSTATINE CONTAINING POLYPEPTIDES
  申请人：PFIZER INC.

  公开号：WO1987002675A1

  公开（公告）日：1987-05-07

  (EN) Polypeptides and derivatives thereof containing 2,2-difluorocyclostatine are useful for inhibiting the angiotensinogen-cleaving action of the enzyme renin.(FR) Sont décrits des polypeptides et leurs dérivés contenant 2,2-difluorocyclostatine, lesquels sont utiles pour inhiber l'action de clivage sur l'angiotensinogène de la rénine enzymatique.
• Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors
  作者：William C. Patt、Harriet W. Hamilton、Michael D. Taylor、Michael J. Ryan、David G. Taylor、Cleo J. C. Connolly、Annette M. Doherty、Sylvester R. Klutchko、Ila Sircar

  DOI：10.1021/jm00092a006

  日期：1992.7

  A series of renin inhibitors was synthesized that contained a 2-amino-4-thiazolyl moiety at the P2 position. These derivatives are potent inhibitors of monkey renin in vitro and are selective in that they only weakly inhibit the closely related aspartic proteinase, bovine cathepsin D. Four compounds exhibited oral blood pressure lowering activity in high-renin normotensive monkeys. One of these compounds, 22 (PD 134672), was selected for further evaluation in renal hypertensive monkeys, on the basis of its superior efficacy and duration of action in the in vitro assays and the normotensive primate model.