perhydroindoline-2(S)-carboxylic acid hydrochloride | 97975-67-2

• 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: perhydroindoline-2(S)-carboxylic acid hydrochloride
• 英文别名: 1α,3β,5α 2-azabicyclo[4.3.0]nonane-3-carboxylic acid hydrochloride；(2α, 3aβ, 7aβ)-octahydro-1H-indole-2-carboxylic acid hydrochloride；(2S,3aS,7aS)-octahydro-1H-indole-2-carboxylic acid hydrochloride；(2S,3aS,7aS)-2,3,3a,4,5,6,7,7a-octahydro-1H-indole-2-carboxylic acid;hydrochloride
• CAS: 97975-67-2
• 化学式: C₉H₁₅NO₂*ClH
• 分子量: 205.685
• InChiKey: PONAUWFRJYNGAC-WQYNNSOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.41
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  49.3
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [(3R)-四氢-2,6-二氧代-2H-吡喃-3-基]-氨基甲酸苯基甲基 、 perhydroindoline-2(S)-carboxylic acid hydrochloride 在 吡啶 作用下， 反应 5.0h， 以53%的产率得到1-(N-苄氧羰基-gamma-谷氨酰)全氢吲哚啉-2-羧酸
  参考文献：
  名称：

  Angiotensin converting enzyme inhibitors: N-substituted D-glutamic acid .gamma.-dipeptides

  摘要：

  The preparation of two series of N-carbobenzoxy-gamma-D-glutamyl secondary 2S amino acids and (N-substituted gamma-D-glutamyl)indoline-2(S)-carboxylic acid dipeptides is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound, and the structure-activity relationship is discussed. Oral and iv inhibition of AI pressor response in vivo of selected compounds in Table II is also discussed. The most potent compounds in vitro, 3 and 6a, had an ACE IC50 of 7 and 2.7 X 10(-9) M, respectively.

  DOI：

  10.1021/jm00149a011
• 作为产物：
  描述：

  3,3a,4,5,6,7-2H-hexahydroindole-2-carboxylic acid hydrochloride 在 platinum on activated charcoal 氢气 、 溶剂黄146 作用下， 生成 perhydroindoline-2(S)-carboxylic acid hydrochloride
  参考文献：
  名称：

  Process for the preparation of perindopril and salts thereof

  摘要：

  本发明描述了一种新的方法，用于合成(2S,3aS,7aS)-八氢吲哚-2-羧酸或其式XIII的芳基酯之一，其中X和Y是氢原子、卤素、烷基、烷氧基或硝基基团，并将式X的对硝基苄酯转化为公益普利或其盐之一的式I。

  公开号：

  EP1864973A1

文献信息

• [EN] A NOVEL SYNTHESIS OF 2-AZABICYCLIC-3-CARBOXYLIC ACIDS, USEFUL AS IMPORTANT DRUG INTERMEDIATES<br/>[FR] NOUVELLE SYNTHESE DES ACIDES 2-AZABICYCLIQUES-3-CARBOXYLIQUES UTILISES COMME INTERMEDIAIRES MEDICAMENTAUX IMPORTANTS
  申请人：BABU POTLURI RAMESH

  公开号：WO2005049567A1

  公开（公告）日：2005-06-02

  A novel process for the preparation of 2-azabicyclo-3-carboxylic acid hydrochloride of formula (I), by reacting the compound of formula (II) with an acylating agent in a non-polar solvent at 0-150 °C to give a compound of formula (III), which is reacted with an enamine of formula (IV) in a non-polar solvent in the presence of an organic base at 0 °C to 150 °C to yield a compound of formula (V), which is hydrolytically cyclised to give a compound of formula (VI) and further catalytically hydrogenated to give the compound of formula (I).

  一种用于制备式（I）的2-氮杂双环-3-羧酸盐酸盐的新型方法，通过将式（II）的化合物与非极性溶剂中的酰化剂在0-150°C下反应，得到式（III）的化合物，然后在有机碱存在下，将式（III）的化合物与式（IV）的烯胺在0°C至150°C的非极性溶剂中反应，得到式（V）的化合物，将其水解环化得到式（VI）的化合物，进一步进行催化氢化得到式（I）的化合物。
• Substituted acyl derivatives of octahydro-1H-indole-2-carboxylic acids
  申请人：Warner-Lambert Company

  公开号：US04350704A1

  公开（公告）日：1982-09-21

  Substituted acyl derivatives of octahydro-1H-indole-2-carboxylic acid and the pharmaceutically acceptable salts thereof are produced by acylating a suitably substituted octahydro-1H-indole with a suitably activated substituted carboxylic acid and when desired hydrolyzing the resulting product. The compounds of the invention, their salts and pharmaceutical compositions thereof are useful as antihypertensive agents.

  本发明提供了八氢-1H-吲哚-2-羧酸的取代酰基衍生物及其药学上可接受的盐，通过用适当活化的取代羧酸酰化适当取代的八氢-1H-吲哚，当需要时水解产物。本发明的化合物、其盐和药物组成物作为降压剂有用。
• Tripeptide derivatives
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：EP0244836A2

  公开（公告）日：1987-11-11

  A tripeptide derivative represented by the following formula wherein R1 represents a C1-10 alkyl group, a C4-7 cyclomny or C5-7 cycloalkyl-lower alkyl group, a phenyl or phenyl-lower alkyl group in which the benzene ring may optionally be substituted by a substituent selected from halogen, lower alkyl, lower alkoxy, phenyl, methylenedioxy, ethylenedioxy, amino, di(lower alkyl)amino and hydroxy, a naphthyl or naphthyl-lower alkyl group in which the naphthalene ring may optionally be substituted by a substituent selected from halogen, lower alkyl, lower alkoxy and hydroxy, a heterocyclic or heterocyclic-lower alkyl group in which the heterocycle is a saturated or unsaturated 5- or 6-membered ring containing a nitrogen, oxygen or sulfur atom as the hetero atom, and may optionally be substituted by a substituent selected from halogen, lower alkyl, lower alkoxy, amino, di(lower alkyl)amino, hydroxy, oxo and saturated 5- or 6-membered nitrogen-containing heterocyclic group, and further may optionally be fused to a benzene ring, or an imidazolylvinyl group; R2 represents a hydrogen atom, a C1-10 alkyl group or a benzyl group; R3 represents a group of the formula in which ( represents a benzene, cyclopentane or cyclohexane ring, R4 represents a hydrogen atom, a C1-10 alkyl group or a benzyl group, p is 0 or 1, q is 1, or 3, and X represents a phenyl group which may optionally be substituted by a substituent selected from halogen, lower alkoxy and hydroxy, a C4-8 cycloalkyl group, or a C5-7 cycloalkyl group which is fused to a benzene, and Y represents a hydrogen atom or a lower alkyl group, or X and Y, together with the nitrogen and carbon atoms to which they are bonded, forms a 5- or 6-membered heterocyle which may contain a nitrogen, oxygen or sulfur atom, W represents a single bond, -O- or -NH-, T represents a single bond, or-S-, and m is 2 or 3, or salts thereof; processes for production thereof; and the use thereof as a medicine, particularly an anti-hypertensive agent.

  下式所代表的三肽衍生物 其中 R1 代表 C1-10 烷基、C4-7 环烷基或 C5-7 环烷基-低级烷基、苯基或苯基-低级烷基，其中苯环可任选被选自卤素、低级烷基、低级烷氧基、苯基、亚甲基二氧基、亚乙基二氧基、氨基、二(低级烷基)氨基和羟基的取代基取代；萘基或萘基-低级烷基，其中萘环可任选被选自卤素、低级烷基、低级烷氧基和羟基的取代基取代；杂环或杂环-低级烷基，其中杂环是饱和或不饱和的 5-或 5-(低级烷基)萘环、杂环或杂环-低级烷基基团，其中杂环是饱和或不饱和的 5 或 6 元环，含氮、氧或硫原子作为杂原子，并可选择被选自卤素、低级烷基、低级烷氧基、低级烷氧基和羟基的取代基取代、低级烷基、低级烷氧基、氨基、二（低级烷基）氨基、羟基、氧代和饱和的 5 或 6 元含氮杂环基团，还可任选与苯环或咪唑乙烯基融合；R2 代表氢原子、C1-10 烷基或苄基； R3 代表如下式的基团 其中 ( 代表苯环、环戊烷环或环己烷环，R4 代表氢原子、C1-10 烷基或苄基，p 为 0 或 1，q 为 1 或 3，X 代表苯基，可任选被选自卤素、低级烷氧基和羟基的取代基取代、一个 C4-8 环烷基，或一个与苯融合的 C5-7 环烷基，Y 代表一个氢原子或一个低级烷基，或 X 和 Y 与它们所键合的氮原子和碳原子一起形成一个 5 或 6 元杂环，该杂环可包含一个氮原子、氧原子或硫原子、 W 代表单键、-O- 或-NH-，T 代表单键、 或-S-，m 为 2 或 3、 或其盐类；其生产工艺；以及其作为药物，特别是抗高血压药物的用途。
• 一种培哚普利中间体(2S,3aS,7aS)-八氢吲哚-2-羧酸制备方法
  申请人：浙江华海药业股份有限公司

  公开号：CN116199613A

  公开（公告）日：2023-06-02

  本发明涉及培哚普利主要中间体如式Ⅰ(2S,3aS,7aS)‑八氢吲哚‑2‑羧酸制备方法。以N‑酰基甘氨酸衍生物为原料，经一步或多步得到4‑(烷氧基亚甲基)‑2‑烷基恶唑酮中间体式Ⅱ；中间体式Ⅱ与各种N‑(1‑环己烯基)胺室温下反应得到中间体式Ⅲ；中间体式Ⅲ在催化量烷基醇盐条件下醇解生成不饱和氨基酸中间体式Ⅳ；中间式Ⅳ在过渡金属铑‑手性膦配体络合物催化剂条件下生成对映体富集中间体式Ⅴ(包括式Va和式Vb)；中间体式Ⅴb在盐酸以及催化量钯碳条件下生成式Ⅰ(2S,3aS,7aS)‑八氢吲哚‑2‑羧酸。该工艺具有收率较高、工艺简单、环境友好等特点，具有较好的产业化应用前景。
• 1-CARBOXYALKANOYLPERHYDROINDOLE-2-CARBOXYLIC ACIDS AND DERIVATIVES
  申请人：CIBA-GEIGY AG

  公开号：EP0105919A1

  公开（公告）日：1984-04-25