3(R)-[1(S)-carboxy-7-(4-piperidyl)heptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid | 100303-35-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: 3(R)-[1(S)-carboxy-7-(4-piperidyl)heptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid
• 英文别名: (2S)-2-[[(3R)-5-(carboxymethyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl]amino]-8-piperidin-4-yloctanoic acid
• CAS: 100303-35-3
• 化学式: C₂₄H₃₅N₃O₅S
• 分子量: 477.625
• InChiKey: AXOCJZRIOLWDCH-OALUTQOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  144
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tert-butyl (R)-3-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate 在 sodium hydroxide 、 molecular sieve 、 氢溴酸 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 2.25h， 生成 3(R)-[1(S)-carboxy-7-(4-piperidyl)heptyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid
  参考文献：
  名称：

  Synthesis and angiotensin converting enzyme-inhibitory activity of 1,5-benzothiazepine and 1,5-benzoxazepine derivatives. III.

  摘要：

  一系列具有(S)-1-羧基-ω-(4-哌啶基)烷基基团的(R)-3-氨基-4-氧代-2, 3, 4, 5-四氢-1, 5-苯噻氮卓-5-乙酸（8）和(S)-3-氨基-4-氧代-2, 3, 4, 5-四氢-1, 5-苯并噻氮卓-5-乙酸（9）被制备，作为寻找具有长效作用的血管紧张素转化酶（ACE）抑制剂的一部分。在哌啶基烷基部分中，碳链的长度(n)从二到六进行了变化，以确定最佳结构。在静脉注射和口服给药中，观察到(R)-3-[(S)-1-羧基-5-(4-哌啶基)戊基]氨基-4-氧代-2, 3, 4, 5-四氢-1, 5-苯噻氮卓-5-乙酸（8c：CV-5975）具有最持久的体内活性。

  DOI：

  10.1248/cpb.34.3747

文献信息

• Intermediates for the preparation of condensed seven-membered ring
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04739066A1

  公开（公告）日：1988-04-19

  Novel condensed seven-membered ring compounds of the formula: ##STR1## [wherein R.sup.1 and R.sup.2 are independently hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy, or both jointly form tri- or tetramethylene; R.sup.3 and R.sup.5 are independently hydrogen, lower alkyl or aralkyl; R.sup.4 is hydrogen or lower alkyl; R.sup.6 is a condensed or non-condensed hetero-alicyclic containing at least one atom of N, O and S as a ring-forming atom which may be substituted; A is an alkylene chain; n is 1 or 2] and salts thereof. These compounds exhibit inhibitory activity on angiotensin converting enzyme and so forth, and are of value as an agent for diagnosis, prevention and treatment of circulatory diseases, such as hypertension, cardiopathy and cerebral apoploxy.

  这是一种化合物的化学式：##STR1## [其中R.sup.1和R.sup.2分别为氢、卤素、三氟甲基、低碳基或低碳氧基，或共同形成三亚甲基或四亚甲基；R.sup.3和R.sup.5分别为氢、低碳基或芳基低碳基；R.sup.4为氢或低碳基；R.sup.6为含有至少一个N、O和S原子作为环形成原子的紧缩或非紧缩杂环，可以被取代；A是一个烷基链；n为1或2]和它们的盐。这些化合物表现出对血管紧张素转换酶等的抑制活性，并且作为诊断、预防和治疗循环系统疾病（如高血压、心脏病和脑中风）的药物具有价值。
• Condensed seven-membered ring compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04638000A1

  公开（公告）日：1987-01-20

  Novel condensed seven-membered ring compounds of the formula: ##STR1## [wherein R.sup.1 and R.sup.2 are independently hydrogen, halogen, trifluoromethyl, lower alkyl or lower alkoxy, or both jointly form tri- or tetramethylene; R.sup.3 and R.sup.5 are independently hydrogen, lower alkyl or aralkyl; R.sup.4 is hydrogen or lower alkyl; R.sup.6 is a condensed or non-condensed hetero-alicyclic containing at least one atom of N, O and S as a ring-forming atom which may be substituted; A is an alkylene chain; n is 1 or 2] and salts thereof. These compounds exhibit inhibitory activity on angiotensin converting enzyme and so forth, and are of value as an agent for diagnosis, prevention and treatment of circulatory diseases, such as hypertension, cardiopathy and cerebral apoploxy.

  这是一种化合物，其化学式为：##STR1## 其中R1和R2可以独立地是氢、卤素、三氟甲基、低碳基或低碳氧基，或者共同形成三元或四元亚甲基；R3和R5可以独立地是氢、低碳基或芳基低碳基；R4是氢或低碳基；R6是含有至少一个N、O和S原子作为环形成原子的紧缩或非紧缩杂环，可以被取代；A是一个烷基链；n为1或2。这些化合物表现出抑制血管紧张素转化酶等的活性，并且在诊断、预防和治疗循环系统疾病，如高血压、心脏病和脑卒中方面具有价值。
• US4638000A
  申请人：——

  公开号：US4638000A

  公开（公告）日：1987-01-20
• US4739066A
  申请人：——

  公开号：US4739066A

  公开（公告）日：1988-04-19
• Synthesis and angiotensin converting enzyme-inhibitory activity of 1,5-benzothiazepine and 1,5-benzoxazepine derivatives. III.
  作者：KATSUMI ITOH、MASAKUNI KORI、YOSHIYUKI INADA、KOHEI NISHIKAWA、YUTAKA KAWAMATSU、HIROSADA SUGIHARA

  DOI：10.1248/cpb.34.3747

  日期：——

  A seires of (R)-3-amino-4-oxo-2, 3, 4, 5-tetrahydro-1, 5-benzothiazepine-5-acetic acids (8) and (S)-3-amino-4-oxo-2, 3, 4, 5-tetrahydro-1, 5-benzoxazepine-5-acetic acids (9) having an (S)-1-carboxy-ω-(4-piperidyl)alkyl group on the amino group at the 3-position was prepared as part of a search for long-acting inhibitors of the angiotensin converting enzyme (ACE). The length (n) of the carbon chain in the piperidylalkyl moiety was varied from two six in order to determine the optimal structure. The most prolonged activity in vivo was observed with (R)-3-[(S)-1-carboxy-5-(4-piperidyl)pentyl]amino-4-oxo-2, 3, 4, 5-tetrahydro-1, 5-benzothiazepine-5-acetic acid (8c : CV-5975) on i.v. and p.o. administrations.

  一系列具有(S)-1-羧基-ω-(4-哌啶基)烷基基团的(R)-3-氨基-4-氧代-2, 3, 4, 5-四氢-1, 5-苯噻氮卓-5-乙酸（8）和(S)-3-氨基-4-氧代-2, 3, 4, 5-四氢-1, 5-苯并噻氮卓-5-乙酸（9）被制备，作为寻找具有长效作用的血管紧张素转化酶（ACE）抑制剂的一部分。在哌啶基烷基部分中，碳链的长度(n)从二到六进行了变化，以确定最佳结构。在静脉注射和口服给药中，观察到(R)-3-[(S)-1-羧基-5-(4-哌啶基)戊基]氨基-4-氧代-2, 3, 4, 5-四氢-1, 5-苯噻氮卓-5-乙酸（8c：CV-5975）具有最持久的体内活性。