PD 134672 | 135704-06-2

• 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: PD 134672
• 英文别名: <1S-(1R*,2S*,3R*)>-N-(4-morpholinylsulfonyl)-L-phenylalanyl-3-(2-amino-4-thiazolyl)-N-<1-(cyclohexylmethyl)-2,3-dihydroxy-5-methylhexyl>-L-alaninamide；(S)-N-[(S)-2-(2-Amino-thiazol-4-yl)-1-((1S,2R,3S)-1-cyclohexylmethyl-2,3-dihydroxy-5-methyl-hexylcarbamoyl)-ethyl]-2-(morpholine-4-sulfonylamino)-3-phenyl-propionamide；(2S)-N-[(2S)-3-(2-amino-1,3-thiazol-4-yl)-1-[[(2S,3R,4S)-1-cyclohexyl-3,4-dihydroxy-6-methylheptan-2-yl]amino]-1-oxopropan-2-yl]-2-(morpholin-4-ylsulfonylamino)-3-phenylpropanamide
• CAS: 135704-06-2
• 化学式: C₃₃H₅₂N₆O₇S₂
• 分子量: 708.944
• InChiKey: QGJKHQRFJGLJLV-VFFRCKCKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  48
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  233
• 氢给体数：
  6
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  PD 134672 在 盐酸 作用下， 以 氯仿 为溶剂， 反应 3.0h， 生成 (S)-3-(2-Amino-thiazol-4-yl)-2-[(S)-2-(morpholine-4-sulfonylamino)-3-phenyl-propionylamino]-propionic acid (1S,2R,3S)-3-amino-4-cyclohexyl-2-hydroxy-1-isobutyl-butyl ester; hydrochloride 、 (S)-3-(2-Amino-thiazol-4-yl)-2-[(S)-2-(morpholine-4-sulfonylamino)-3-phenyl-propionylamino]-propionic acid (1R,2S)-1-((S)-1-amino-2-cyclohexyl-ethyl)-2-hydroxy-4-methyl-pentyl ester; hydrochloride
  参考文献：
  名称：

  含肾素抑制剂的β，γ-双羟基酰胺的口服活性水溶性N，O-酰基转移产物。

  摘要：

  DOI：

  10.1021/jm00062a024
• 作为产物：
  描述：

  (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6-methylheptane 在 盐酸 、 氯化铵 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 PD 134672
  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

• 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.
• Orally active water-soluble N,O-acyl transfer products of a .beta.,.gamma.-bishydroxyl amide containing renin inhibitor
  作者：Timothy R. Hurley、Charles E. Colson、Gary Hicks、Michael J. Ryan

  DOI：10.1021/jm00062a024

  日期：1993.5