(3S)-2-(3-benzoylthio-2-methylpropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid | 77832-25-8

• 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: (3S)-2-(3-benzoylthio-2-methylpropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
• 英文别名: (3S)-2-(3-benzoylsulfanyl-2-methylpropanoyl)-3,4-dihydro-1H-isoquinoline-3-carboxylic acid
• CAS: 77832-25-8；77832-29-2；77972-27-1
• 化学式: C₂₁H₂₁NO₄S
• 分子量: 383.468
• InChiKey: CHKWLKYLLOEVHG-IBYPIGCZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  100
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (D)-3-(benzoylthio)-2-methylpropanoic acid chloride 在 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 生成 (3S)-2-(3-benzoylthio-2-methylpropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Studies on angiotensin-converting enzyme inhibitors. I. Syntheses and angiotensinconverting enzyme inhibitory activity of 2-(3-mercaptopropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives.

  摘要：

  (3S)-2-[(2S)-3-巯基-2-甲基丙酰基]-1, 2, 3, 4-四氢异喹啉-3-羧酸[(3S), (2S)-6a]是通过(3S)-1, 2, 3, 4-四氢异喹啉-3-羧酸叔丁基酯[(3S)-2a]或苄基酯[(3S)-2b]与3-苯甲酰硫-2-甲基丙酰氯(3a)反应制备而成，随后通过分馏结晶去除保护基团。通过对由6a衍生的噻唑烯[4, 3-b]异喹啉化合物(7)进行X射线衍射分析，确认了(3S), (2S)-6a的绝对构型。使用光学活性的苯丙氨酸酰胺作为分解剂完成了3-苯甲酰硫-2-甲基丙酸(8)的分解。通过(3S)-或(3R)-2b与光学活性3a反应制备了(3S), (2S)-6a的其他光学异构体。评估了每种6a异构体的体外ACE抑制活性。其中，(3S), (2S)-6a被发现是最有效的抑制剂，IC50值为8.6×10^-9M。化合物(3S), (2S)-6a在该显混合型麻醉大鼠口服给药后，诱导了对血管紧张素I的加压反应的剂量依赖性抑制。此外，(3S), (2S)-6a显著降低了肾性高血压大鼠(RHR)和自发性高血压大鼠(SHR)的收缩压。(3S), (2S)-6a的体内ACE抑制活性和降压效果与卡托普利相当。

  DOI：

  10.1248/cpb.31.570

文献信息

• Tetrahydroisoquinoline derivatives
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US04256751A1

  公开（公告）日：1981-03-17

  A compound of the formula: ##STR1## wherein R.sup.1 is hydrogen or methyl, is prepared by condensing a compound of the formula: ##STR2## wherein R.sup.2 is alkyl, aryl or aralkyl and R.sup.1 is same as above, or a reactive derivative thereof with 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid or an ester thereof to give a compound of the formula: ##STR3## wherein R.sup.3 is an ester residue and R.sup.1 and R.sup.2 are same as above, followed by hydrolysis or ammonolysis of said compound (IV). The compound (I) is useful as a diagnostic or therapeutic agent for angiotensin-related hypertension.

  该公式化合物为：##STR1##其中R.sup.1为氢或甲基，通过将化合物：##STR2##其中R.sup.2为烷基、芳基或芳基烷基，R.sup.1与上述相同，或其活性衍生物与1,2,3,4-四氢异喹啉-3-羧酸或其酯缩合制备化合物：##STR3##其中R.sup.3为酯基，R.sup.1和R.sup.2与上述相同，然后水解或氨解化合物（IV）。该化合物（I）可用作与肾素-血管紧张素系统有关的高血压的诊断或治疗剂。
• Tetrahydroisoquinoline compounds, process for preparing same and pharmaceutical compositions containing them
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：EP0012845A1

  公开（公告）日：1980-07-09

  A compound of the formula: wherein R1 is hydrogen or methyl, is prepared by condensing a compound of the formula: wherein R2 is alkyl, aryl or aralkyl and R1 is same as above, or a reactive derivative thereof with 1,2,3,4,- tetrahydroisoquinoline -3-carboxylic acid or an ester thereof to give a compound of the formula: wherein R3 is an ester residue and R1 and R2 are same as above, followed by hydrolysis or ammonolysis of said com pound (IV). The compound (1) is useful as a diagnostic or therapeutic agent for angiotensin-related hypertension.

  通过将式：其中 R2 为烷基、芳基或芳烷基且 R1 同上的化合物或其反应衍生物与 1，2，3，4，- 四氢异喹啉-3-羧酸或其酯缩合，得到式：其中 R3 为酯残基且 R1 和 R2 同上的化合物，然后将所述化合物（IV）水解或氨解，制备式：其中 R1 为氢或甲基的化合物。 该化合物（1）可用作血管紧张素相关性高血压的诊断或治疗剂。
• US4256751A
  申请人：——

  公开号：US4256751A

  公开（公告）日：1981-03-17
• Studies on angiotensin-converting enzyme inhibitors. I. Syntheses and angiotensinconverting enzyme inhibitory activity of 2-(3-mercaptopropionyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives.
  作者：KIMIAKI HAYASHI、YASUHIKO OZAKI、KENICHI NUNAMI、TOMOFUMI UCHIDA、JYOJI KATO、KEIZO KINASHI、NAOTO YONEDA

  DOI：10.1248/cpb.31.570

  日期：——

  (3S)-2-[(2S)-3-Mercapto-2-methylpropionyl]-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid [(3S), (2S)-6a] was prepared by the reaction of (3S)-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid tert-butyl ester [(3S)-2a] or benzyl ester [(3S)-2b] with 3-benzoylthio-2-methylpropionyl chloride (3a), followed by fractional crystallization and removal of the protective group. The absolute configuration of (3S), (2S)-6a was confirmed by X-ray diffraction analysis of the thiazepino [4, 3-b] isoquinoline compound (7) derived from 6a. Resolution of 3-benzoylthio-2-methylpropionic acid (8) was completed by using optically active phenylalanine amide as a resolving agent. The other optical isomers of (3S), (2S)-6a were prepared by the reaction of (3S)- or (3R)-2b with optically active 3a. The in vitro ACE inhibitory activity of each isomer of 6a was evaluated. Among them, (3S), (2S)-6a was found to be the most potent inhibitor with an IC50 value of 8.6×10-9M. Compound (3S), (2S)-6a induced a dose-dependent inhibition of the pressor response to angiotensin I after oral administration to normotensive anesthetized rats. Moreover, (3S), (2S)-6a markedly reduced the systolic blood pressure in renal hypertensive rats (RHR) and spontaneously hypertensive rats (SHR). The in vivo ACE inhibitory activity and the hypotensive effects of (3S), (2S)-6a were comparable to those of captopril.

  (3S)-2-[(2S)-3-巯基-2-甲基丙酰基]-1, 2, 3, 4-四氢异喹啉-3-羧酸[(3S), (2S)-6a]是通过(3S)-1, 2, 3, 4-四氢异喹啉-3-羧酸叔丁基酯[(3S)-2a]或苄基酯[(3S)-2b]与3-苯甲酰硫-2-甲基丙酰氯(3a)反应制备而成，随后通过分馏结晶去除保护基团。通过对由6a衍生的噻唑烯[4, 3-b]异喹啉化合物(7)进行X射线衍射分析，确认了(3S), (2S)-6a的绝对构型。使用光学活性的苯丙氨酸酰胺作为分解剂完成了3-苯甲酰硫-2-甲基丙酸(8)的分解。通过(3S)-或(3R)-2b与光学活性3a反应制备了(3S), (2S)-6a的其他光学异构体。评估了每种6a异构体的体外ACE抑制活性。其中，(3S), (2S)-6a被发现是最有效的抑制剂，IC50值为8.6×10^-9M。化合物(3S), (2S)-6a在该显混合型麻醉大鼠口服给药后，诱导了对血管紧张素I的加压反应的剂量依赖性抑制。此外，(3S), (2S)-6a显著降低了肾性高血压大鼠(RHR)和自发性高血压大鼠(SHR)的收缩压。(3S), (2S)-6a的体内ACE抑制活性和降压效果与卡托普利相当。