(2S,3S)-2-hydroxy-3-<(2-amino-5-methoxyphenyl)thio>-3-(4-methoxyphenyl)propionic acid | 132618-98-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (2S,3S)-2-hydroxy-3-<(2-amino-5-methoxyphenyl)thio>-3-(4-methoxyphenyl)propionic acid
• 英文别名: (2S,3S)-3-(2-amino-5-methoxyphenyl)sulfanyl-2-hydroxy-3-(4-methoxyphenyl)propanoic acid
• CAS: 132618-98-5
• 化学式: C₁₇H₁₉NO₅S
• 分子量: 349.408
• InChiKey: RROVHCWZFGVBRY-CVEARBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2-hydroxy-3-<(2-amino-5-methoxyphenyl)thio>-3-(4-methoxyphenyl)propionic acid 在 盐酸 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.83h， 生成 (2S,3S)-3-Hydroxy-8-methoxy-2-(4-methoxy-phenyl)-5-(S)-1-pyrrolidin-2-ylmethyl-2,3-dihydro-5H-benzo[b][1,4]thiazepin-4-one
  参考文献：
  名称：

  Benzazepinone calcium channel blockers. 5. Effects on antihypertensive activity associated with N1 and aromatic substituents

  摘要：

  We have shown that the pyrrolidinylmethyl substituent on the lactam nitrogen (Nl) of benzazepinone and benzothiazepinone calcium channel blocking agents is resistant to metabolic deamination and generally increases the duration and potency of antihypertensive activity in spontaneously hypertensive rats (SHR) relative to (N,N-dimethylamino) ethyl analogs. Additionally, compounds possessing a substituent on the fused aromatic ring are more resistant to metabolic deacylation of the C3 hydroxy function, which may explain why aromatic substituents also frequently increase the potency and/or duration of antihypertensive activity. Our data also indicate the in antihypertensive activity associated with these structural modifications is independent of any effects of potency in vitro. Overall, we interpret these results to indicate that these structural modifications improve antihypertensive activity as a result of increased metabolic stability and, consequently, oral bioavailability.

  DOI：

  10.1021/jm00092a011
• 作为产物：
  描述：

  (2S,3S)-2-hydroxy-3-<(2-amino-5-methoxyphenyl)thio>-3-(4-methoxyphenyl)propionic acid methyl ester D-(-)-tartaric acid salt 在 甲醇 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 1.0h， 以98%的产率得到(2S,3S)-2-hydroxy-3-<(2-amino-5-methoxyphenyl)thio>-3-(4-methoxyphenyl)propionic acid
  参考文献：
  名称：

  Benzazepinone calcium channel blockers. 5. Effects on antihypertensive activity associated with N1 and aromatic substituents

  摘要：

  We have shown that the pyrrolidinylmethyl substituent on the lactam nitrogen (Nl) of benzazepinone and benzothiazepinone calcium channel blocking agents is resistant to metabolic deamination and generally increases the duration and potency of antihypertensive activity in spontaneously hypertensive rats (SHR) relative to (N,N-dimethylamino) ethyl analogs. Additionally, compounds possessing a substituent on the fused aromatic ring are more resistant to metabolic deacylation of the C3 hydroxy function, which may explain why aromatic substituents also frequently increase the potency and/or duration of antihypertensive activity. Our data also indicate the in antihypertensive activity associated with these structural modifications is independent of any effects of potency in vitro. Overall, we interpret these results to indicate that these structural modifications improve antihypertensive activity as a result of increased metabolic stability and, consequently, oral bioavailability.

  DOI：

  10.1021/jm00092a011

文献信息

• Benzazepinone calcium channel blockers. 5. Effects on antihypertensive activity associated with N1 and aromatic substituents
  作者：Jagabandhu Das、David M. Floyd、S. David Kimball、Keith J. Duff、Michael W. Lago、John Krapcho、Ronald E. White、Richard E. Ridgewell、Mary T. Obermeier

  DOI：10.1021/jm00092a011

  日期：1992.7

  We have shown that the pyrrolidinylmethyl substituent on the lactam nitrogen (Nl) of benzazepinone and benzothiazepinone calcium channel blocking agents is resistant to metabolic deamination and generally increases the duration and potency of antihypertensive activity in spontaneously hypertensive rats (SHR) relative to (N,N-dimethylamino) ethyl analogs. Additionally, compounds possessing a substituent on the fused aromatic ring are more resistant to metabolic deacylation of the C3 hydroxy function, which may explain why aromatic substituents also frequently increase the potency and/or duration of antihypertensive activity. Our data also indicate the in antihypertensive activity associated with these structural modifications is independent of any effects of potency in vitro. Overall, we interpret these results to indicate that these structural modifications improve antihypertensive activity as a result of increased metabolic stability and, consequently, oral bioavailability.