(S)-2-((2S,6R)-4-tert-Butoxycarbonylmethyl-5-oxo-2-thiophen-2-yl-[1,4]thiazepan-6-ylamino)-4-phenyl-butyric acid ethyl ester | 110221-37-9

• 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-((2S,6R)-4-tert-Butoxycarbonylmethyl-5-oxo-2-thiophen-2-yl-[1,4]thiazepan-6-ylamino)-4-phenyl-butyric acid ethyl ester
• 英文别名: ethyl (2S)-2-[[(2S,6R)-4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-5-oxo-2-thiophen-2-yl-1,4-thiazepan-6-yl]amino]-4-phenylbutanoate
• CAS: 110221-37-9
• 化学式: C₂₇H₃₆N₂O₅S₂
• 分子量: 532.725
• InChiKey: XNHPLAAFMMJUIC-FUDKSRODSA-N

物化性质

• 沸点：
  679.6±55.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 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-((2S,6R)-4-tert-Butoxycarbonylmethyl-5-oxo-2-thiophen-2-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78%的产率得到盐酸替莫普利
  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-((2S,6R)-4-tert-Butoxycarbonylmethyl-5-oxo-2-thiophen-2-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

• Synthesis of 1,4-Thiazepine Derivatives Having Angiotensin-Converting Enzyme Inhibitory Property
  作者：Hiroaki Yanagisawa、Sadao Ishihara、Akiko Ando、Takuro Kanazaki

  DOI：10.1246/cl.1989.137

  日期：1989.1

  Reduction of (6R)-6-amino-6,7-dihydro-2-thienyl-1,4-thiazepin-5(4H)-one derivatives with Mg–MeOH gave the corresponding perhydrothiazepinones. Protection with trityl group at the 6-amino group gave predominantly the 2S,6R isomer which was converted to the potent angiotensin-converting enzyme (ACE) inhibitor. The ACE inhibitor having the 6,7-dihydro-l,4-thiazepin-5(4H)-one ring was also prepared.

  用镁-甲醇还原（6R）-6-氨基-6,7-二氢-2-噻吩基-1,4-硫氮杂卓-5（4H）-酮衍生物，得到相应的全氢硫氮杂卓酮。在6-氨基基团上用三苯甲基保护基保护，主要得到2S,6R异构体，将其转化为强效血管紧张素转换酶（ACE）抑制剂。还制备了具有6,7-二氢-1,4-硫氮杂卓-5（4H）-酮环的ACE抑制剂。
• YANAGISAVA, XIROAKI;ISIXARA, SADAO;ANDO, AKIKO;KANADZAKI, TAKUO
  作者：YANAGISAVA, XIROAKI、ISIXARA, SADAO、ANDO, AKIKO、KANADZAKI, TAKUO

  DOI：——

  日期：——
• 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：——
• Angiotensin-converting enzyme inhibitors. Perhydro-1,4-thiazepin-5-one derivatives
  作者：Hiroaki Yanagisawa、Sadao Ishihara、Akiko Ando、Takuro Kanazaki、Shuichi Miyamoto、Hiroyuki Koike、Yasuteru Iijima、Kiyoshi Oizumi、Yoichi Matsushita、Tadashi Hata

  DOI：10.1021/jm00394a009

  日期：1987.11

  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.