(R)-3-<(S)-ω-amino-1-carboxypentyl>amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid | 94604-91-8

• 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: (R)-3-<(S)-ω-amino-1-carboxypentyl>amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid
• 英文别名: 3(R)-[5-amino-1(S)-carboxypentyl]-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid；3(R)-[5-amino-1(S)-carboxypentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid；(R)-3-((S)-ω-amino-1-carboxypentyl)amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid；(2S)-6-amino-2-[[(3R)-5-(carboxymethyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl]amino]hexanoic acid
• CAS: 94604-91-8
• 化学式: C₁₇H₂₃N₃O₅S
• 分子量: 381.453
• InChiKey: SINLFURYDIOSFE-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -4
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  158
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (R)-2-bromo-6-phthalimidohexanoic acid 在 盐酸 、 sodium hydroxide 、 硫酸 、 碳酸氢钠 、 一水合肼 、 三乙胺 作用下， 以 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 52.0h， 生成 (R)-3-<(S)-ω-amino-1-carboxypentyl>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. II.

  摘要：

  一系列具有(S)-ω-氨基-1-羧基烷胺基的(R)-3-氨基-4-氧代-2,3,4,5-四氢-1,5-苯并噻二嗪-5-乙酸(4和13)以及(S)-3-氨基-4-氧代-2,3,4,5-四氢-1,5-苯并噁二嗪-5-乙酸(5和14)作为我们寻找长效血管紧张素转换酶(ACE)抑制剂的一部分被合成。多个衍生物显示出强大的体外和体内ACE抑制活性。该系列化合物的结构-活性关系表明，体内ACE抑制活性的持续时间取决于3-位上ω-氨基烷胺取代基的碳链长度。具有最长活性的是(S)-8-氨基-1-羧基辛胺基衍生物(4d和5d)。

  DOI：

  10.1248/cpb.34.2078

文献信息

• Condensed, seven-membered ring compounds and their use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04564612A1

  公开（公告）日：1986-01-14

  Novel condensed, seven-membered ring compounds of the formula: ##STR1## [wherein R.sup.1 and R.sup.2 each represent hydrogen, halogen, trifluoromethyl, lower alkyl or alkoxy, or both jointly form tri- or tetramethylene; R.sup.3 is hydrogen, lower alkyl or aralkyl; R.sup.4 is hydrogen or alkyl, aralkyl or cycloalkylalkyl which may be substituted; X is a group represented by the formula S(O).sub.n (where n is an integer of 0 to 2); Y is a carboxyl group which may be esterified or amidated; m 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 hypertension.

  这些小说中的新型缩合七元环化合物的化学式为：[其中R.sup.1和R.sup.2分别表示氢、卤素、三氟甲基、低碳基或烷氧基，或者共同形成三元或四元亚甲基；R.sup.3为氢、低碳基或芳基烷基；R.sup.4为氢或烷基、芳基烷基或环烷基烷基，可被取代；X为由S(O).sub.n（其中n为0至2的整数）表示的基团；Y为可酯化或酰胺化的羧基；m为1或2]及其盐。这些化合物表现出对血管紧张素转换酶等的抑制活性，并且在高血压的诊断、预防和治疗方面具有价值。
• 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.

  该文献介绍了一类新型的七元环化合物，化学式为：##STR1## [其中R.sup.1和R.sup.2独立地是氢、卤素、三氟甲基、低碳基或低氧基，或共同形成三或四亚甲基；R.sup.3和R.sup.5独立地是氢、低碳基或芳基碳基；R.sup.4是氢或低碳基；R.sup.6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，该杂环可能被取代；A是一种烷基链；n为1或2]及其盐。这些化合物表现出抑制肾素-血管紧张素转化酶等活性，并且在循环疾病的诊断、预防和治疗中具有价值，如高血压、心脏病和脑中风。
• 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：EP0125056A2

  公开（公告）日：1984-11-14

  Novel condensed, seven-membered ring compounds of formula: wherein R' and R2 each represent hydrogen, halogen, trif- fluoromethyl, lower alkyl or alkoxy, or both jointly form tri-or imethylene; R' is hydrogen, lower alkyl or aralkyl; R4 is alogen or alkyl, aralkyl or cyclo-alkytalkyl which may be stituted; X is a group represented by the formula S(O)n ere n is an integer of 0 to 2); Y is a carboxyl group which be esterified or amidated; m is 1 or 2) and salts thereof. These compounds exhibit inhibitory activity on angioten- converting enzyme and so forth, and are of value as an it for diagnosis, prevention and treatment of hypertension.

  式中的新型缩合七元环化合物： 其中，R'和 R2 各自代表氢、卤素、三氟甲基、低级烷基或烷氧基，或两者共同形成三或亚乙基；R'是氢、低级烷基或芳烷基；R4 是烯基或烷基、芳烷基或环烷基，可被取代；X 是由式 S(O)n 代表的基团，n 是 0 至 2 的整数；Y 是羧基，可被酯化或酰胺化；m 是 1 或 2）及其盐类。这些化合物对血管紧张素转换酶等具有抑制活性，具有诊断、预防和治疗高血压的价值。
• One-pot process for preparation of 7beta-amino- and 7beta-acylamino- 3-substituted methyl-3-cephem-4-carboxylic acid derivatives and process for deoxygenation of 7beta-acylamino-3-cephem-4-carboxylic acid 1-oxide derivatives
  申请人：GIST-BROCADES N.V.

  公开号：EP0137534A2

  公开（公告）日：1985-04-17

  Multi-step one-pot process for the preparation of inter alia 7β-amino- and 7β-acylamino-3-substituted methyl-3-cephem-4-carboxylic acid derivatives starting from 7p-acylamino-3-methyl-3-cephem-4-carboxylic acid 1β-oxide derivatives, comprising a new process for deoxygenation of generally 7p-acylamino-3-cephem-4-carboxylic acid 1-oxide derivatives optionally substituted in the 7a-position, which can be applied as single step or can be incorporated in multistep processes without isolation of intermediates. The deoxygenation involves the use of phosphorus pentachloride and an olefine for removal of chlorine at least in part by addition to carbon-carbon double bond. Preferred aspects are lasting protection of reactive substituents by silylation and preparation on industrial scale of generally 7β-amino-3-heterocyclic thiomethyl-3-cephem-4-carboxylic acids starting from suitably 7p-phenylacetamido-3-methyl-3-cephem-4-carboxylic acid 9β-oxide.

  以 7p-acylamino-3-methyl-3-cephem-4-carboxylic acid 1β-oxide 衍生物为起点，制备 7β-amino- 和 7β-acylamino-3-Substituted methyl-3-cephem-4-carboxylic acid 衍生物的多步一步法工艺、包括一种对一般 7p-acylamino-3-cephem-4-carboxylic acid 1-oxide derivatives optionally substituted in the 7a-position 进行脱氧的新工艺，该工艺可作为单一步骤应用，也可并入多步骤工艺而无需分离中间产物。 脱氧涉及使用五氯化磷和烯烃，至少部分地通过与碳碳双键加成来去除氯。 优选的方面是通过硅烷化对活性取代基进行持久保护，并以适当的 7p- 苯乙酰氨基-3-甲基-3-头孢-4-羧酸 9β-氧化物为起点，在工业规模上制备一般的 7β-氨基-3-杂环硫甲基-3-头孢-4-羧酸。