methyl (2S)-2-[[(2S)-4-acetylsulfanyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-6-oxohexanoate | 167305-86-4

• 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: methyl (2S)-2-[[(2S)-4-acetylsulfanyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-6-oxohexanoate
• CAS: 167305-86-4
• 化学式: C₂₁H₂₈N₂O₇S
• 分子量: 452.529
• InChiKey: RZCVXZGLHCTMNT-ROUUACIJSA-N

物化性质

• 沸点：
  657.8±55.0 °C(Predicted)
• 密度：
  1.230±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  31
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  153
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[[(2S)-4-acetylsulfanyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-6-oxohexanoate 在 甲醇 、 sodium methylate 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 18.17h， 生成 (3S,7S,11S)-1-aza-3-benzyloxycarbonylamino-11-methoxycarbonyl-2-oxo-6-thiabicyclo[5.4.0]undecane
  参考文献：
  名称：

  Dual Metalloprotease Inhibitors:  Mercaptoacetyl-Based Fused Heterocyclic Dipeptide Mimetics as Inhibitors of Angiotensin-Converting Enzyme and Neutral Endopeptidase

  摘要：

  A series of 7,6- and 7,5-fused bicyclic thiazepinones and oxazepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. These compounds are potent inhibitors of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo. Compound 1a, a 7,6-fused bicyclic thiazepinone, demonstrated excellent blood pressure lowering in a variety of animal models characterized by various levels of plasma renin activity and significantly potentiated urinary sodium, ANP, and cGMP excretion in a cynomolgus monkey assay. On the basis of its potency and duration of action, compound 1a (BMS-186716) was advanced into clinical development for the treatment of hypertension and congestive heart failure.

  DOI：

  10.1021/jm970041e
• 作为产物：
  描述：

  N-Benzyloxycarbonyl-D,L-homocystein-thiolacton 在 N-甲基吗啉 、 氢氧化钾 、 草酰氯 、 1-羟基苯并三唑 、 二甲基亚砜 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 23.5h， 生成 methyl (2S)-2-[[(2S)-4-acetylsulfanyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-6-oxohexanoate
  参考文献：
  名称：

  Dual Metalloprotease Inhibitors:  Mercaptoacetyl-Based Fused Heterocyclic Dipeptide Mimetics as Inhibitors of Angiotensin-Converting Enzyme and Neutral Endopeptidase

  摘要：

  A series of 7,6- and 7,5-fused bicyclic thiazepinones and oxazepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. These compounds are potent inhibitors of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo. Compound 1a, a 7,6-fused bicyclic thiazepinone, demonstrated excellent blood pressure lowering in a variety of animal models characterized by various levels of plasma renin activity and significantly potentiated urinary sodium, ANP, and cGMP excretion in a cynomolgus monkey assay. On the basis of its potency and duration of action, compound 1a (BMS-186716) was advanced into clinical development for the treatment of hypertension and congestive heart failure.

  DOI：

  10.1021/jm970041e

文献信息

• J. Med. Chem. 1997, 40, 1570-1577
  作者：

  DOI：——

  日期：——
• Dual Metalloprotease Inhibitors:  Mercaptoacetyl-Based Fused Heterocyclic Dipeptide Mimetics as Inhibitors of Angiotensin-Converting Enzyme and Neutral Endopeptidase
  作者：Jeffrey A. Robl、Chong-Qing Sun、Jay Stevenson、Denis E. Ryono、Ligaya M. Simpkins、Maria P. Cimarusti、Tamara Dejneka、William A. Slusarchyk、Sam Chao、Leslie Stratton、Raj N. Misra、Mark S. Bednarz、Magdi M. Asaad、Hong Son Cheung、Benoni E. Abboa-Offei、Patricia L. Smith、Parker D. Mathers、Maxine Fox、Thomas R. Schaeffer、Andrea A. Seymour、Nick C. Trippodo

  DOI：10.1021/jm970041e

  日期：1997.5.1

  A series of 7,6- and 7,5-fused bicyclic thiazepinones and oxazepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. These compounds are potent inhibitors of angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) both in vitro and in vivo. Compound 1a, a 7,6-fused bicyclic thiazepinone, demonstrated excellent blood pressure lowering in a variety of animal models characterized by various levels of plasma renin activity and significantly potentiated urinary sodium, ANP, and cGMP excretion in a cynomolgus monkey assay. On the basis of its potency and duration of action, compound 1a (BMS-186716) was advanced into clinical development for the treatment of hypertension and congestive heart failure.
• Drugs of the Future 1999, 24, 269-277
  作者：

  DOI：——

  日期：——