(S)-2-((2R,6R)-4-tert-Butoxycarbonylmethyl-5-oxo-2-thiophen-3-yl-[1,4]thiazepan-6-ylamino)-4-phenyl-butyric acid ethyl ester | 110221-39-1

• 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: (S)-2-((2R,6R)-4-tert-Butoxycarbonylmethyl-5-oxo-2-thiophen-3-yl-[1,4]thiazepan-6-ylamino)-4-phenyl-butyric acid ethyl ester
• 英文别名: ethyl (2S)-2-[[(2R,6R)-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-5-oxo-2-thiophen-3-yl-1,4-thiazepan-6-yl]amino]-4-phenylbutanoate
• CAS: 110221-39-1
• 化学式: C₂₇H₃₆N₂O₅S₂
• 分子量: 532.725
• InChiKey: KKOHWPXFQSDMFE-VABKMULXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-2-((2R,6R)-4-tert-Butoxycarbonylmethyl-5-oxo-2-thiophen-3-yl-[1,4]thiazepan-6-ylamino)-4-phenyl-butyric acid ethyl ester 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以90%的产率得到(S)-2-((2R,6R)-4-Carboxymethyl-5-oxo-2-thiophen-3-yl-[1,4]thiazepan-6-ylamino)-4-phenyl-butyric acid ethyl ester; hydrochloride
  参考文献：
  名称：

  Angiotensin-converting enzyme inhibitors. Perhydro-1,4-thiazepin-5-one derivatives

  摘要：

  alpha-[6-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-5-oxoperhydro -1,4-thiazepin-4-yl]acetic acids (monoester monoacids) and their dicarboxylic acids having the hydrophobic substituents at the 2- or 3-position of the thiazepinone ring were prepared and assayed for angiotensin-converting enzyme (ACE) inhibitory activity. The dicarboxylic acids having the pseudoequatorial amino groups at the 6-position and the pseudoequatorial hydrophobic substituents at the 2- or 3-position of the chair conformation of the thiazepinone ring had potent in vitro inhibitory activity. The monoester monoacids having the hydrophobic substituents at the 2-position suppressed pressor response to angiotensin I for a longer duration than those having the substituents at the 3-position when administered orally. The structure-activity relationship was studied by conformational energy calculations of the thiazepinone ring.

  DOI：

  10.1021/jm00394a009
• 作为产物：
  描述：

  (R)-2-羟基-4-苯基丁酸乙酯 在 吡啶 、 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 (S)-2-((2R,6R)-4-tert-Butoxycarbonylmethyl-5-oxo-2-thiophen-3-yl-[1,4]thiazepan-6-ylamino)-4-phenyl-butyric acid ethyl ester
  参考文献：
  名称：

  Angiotensin-converting enzyme inhibitors. Perhydro-1,4-thiazepin-5-one derivatives

  摘要：

  alpha-[6-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-5-oxoperhydro -1,4-thiazepin-4-yl]acetic acids (monoester monoacids) and their dicarboxylic acids having the hydrophobic substituents at the 2- or 3-position of the thiazepinone ring were prepared and assayed for angiotensin-converting enzyme (ACE) inhibitory activity. The dicarboxylic acids having the pseudoequatorial amino groups at the 6-position and the pseudoequatorial hydrophobic substituents at the 2- or 3-position of the chair conformation of the thiazepinone ring had potent in vitro inhibitory activity. The monoester monoacids having the hydrophobic substituents at the 2-position suppressed pressor response to angiotensin I for a longer duration than those having the substituents at the 3-position when administered orally. The structure-activity relationship was studied by conformational energy calculations of the thiazepinone ring.

  DOI：

  10.1021/jm00394a009

文献信息

• YANAGISAWA, HIROAKI;ISHIHARA, SADAO;ANDO, AKIKO;KANAZAKI, TAKURO;MIYAMOTO+, J. MED. CHEM., 30,(1987) N 11, 1984-1991
  作者：YANAGISAWA, HIROAKI、ISHIHARA, SADAO、ANDO, AKIKO、KANAZAKI, TAKURO、MIYAMOTO+

  DOI：——

  日期：——