N-(2,3-dihydro-1H-inden-2-yl)-N--L-alanyl>-glycine t-butyl ester | 83435-61-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-(2,3-dihydro-1H-inden-2-yl)-N--L-alanyl>-glycine t-butyl ester
• 英文别名: N--L-alanyl>-N-(indan-2-yl)glycine tert-butyl ester；ethyl (S)-2-(((S)-1-((2-(tert-butoxy)-2-oxoethyl)(2,3-dihydro-1H-inden-2-yl)amino)-1-oxopropan-2-yl)amino)-4-phenylbutanoate；tert-butyl N-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-N-(indan-2-yl)glycinate；tert-butyl N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-(S)-alanyl-N-(2-indanyl)glycinate；ethyl (2S)-2-[[(2S)-1-[2,3-dihydro-1H-inden-2-yl-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-4-phenylbutanoate
• CAS: 83435-61-4
• 化学式: C₃₀H₄₀N₂O₅
• 分子量: 508.658
• InChiKey: PRPGLYRIELLIMP-LVXARBLLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  37
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2,3-dihydro-1H-inden-2-yl)-N--L-alanyl>-glycine t-butyl ester 在 盐酸 、 氢溴酸 、 碳酸氢钠 、 溶剂黄146 作用下， 以 水 、 溶剂黄146 、 乙酸乙酯 为溶剂， 反应 0.17h， 生成 盐酸地拉普利
  参考文献：
  名称：

  N- [N-[（S）-1-乙氧基羰基-3-苯基丙基] -L-丙氨酰] -N-（茚满-2-基）甘氨酸（CV-3317）的设计与合成酶抑制剂。

  摘要：

  一种新的血管紧张素转换酶（ACE）抑制剂N-[N-[(S)-1-乙氧基碳基-3-苯基丙基]-L-丙氨酸]-N-(茚-2-基)甘氨酸（9a）是在对ACE抑制剂中C端氨基酸部分的结构要求进行广泛研究后发现的。本文描述了9a的合成及其绝对构型的确定。

  DOI：

  10.1248/cpb.34.2852
• 作为产物：
  描述：

  2-氨基茚 以 二氯甲烷 、 异丙醇 为溶剂， 生成 N-(2,3-dihydro-1H-inden-2-yl)-N--L-alanyl>-glycine t-butyl ester
  参考文献：
  名称：

  Suh; Regan; Skiles, European Journal of Medicinal Chemistry, 1985, vol. 20, # 6, p. 563 - 570

  摘要：

  DOI：

文献信息

• Method for producing indan derivatives
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04835302A1

  公开（公告）日：1989-05-30

  A method for producing an indan derivative represented by the formula: ##STR1## by condensing an N-(.alpha.-alkoxycarbonylaralkyl)-.alpha.-amino acid with an N-(indan-2-yl)glycine alkyl or aralkyl ester in the presence of a diphenyl phosphorochloridate, and a method for producing another indan derivative having anti-hypertensive activity by using the above intermediate indan derivative are useful for industrial production of the indan derivative having anti-hypertensive activity.

  通过在N-(α-烷氧羰基烷基)-α-氨基酸与N-(茚-2-基)甘氨酸烷基或芳基酯在二苯基磷酰氯存在下缩合来制备由下式表示的茚衍生物的方法：##STR1##，并且通过使用上述中间体茚衍生物制备具有抗高血压活性的另一种茚衍生物的方法对于工业生产具有抗高血压活性的茚衍生物是有用的。
• Continuous Flow Synthesis of ACE Inhibitors From N‐Substituted <scp>l</scp> ‐Alanine Derivatives
  作者：Christopher P. Breen、Timothy F. Jamison

  DOI：10.1002/chem.201904400

  日期：2019.11.18

  angiotensin converting enzyme (ACE) inhibitors is described. An optimization effort guided by in situ IR analysis resulted in a general amide coupling approach facilitated by N-carboxyanhydride (NCA) activation that was further characterized by reaction kinetics analysis in batch. The three-step continuous process was demonstrated by synthesizing 8 different ACE inhibitors in up to 88 % yield with throughputs

  描述了一种连续流动合成血管紧张素转化酶（ACE）抑制剂的策略。通过原位IR分析进行的优化工作导致了N-羧基酐（NCA）活化促进的通用酰胺偶联方法，该方法通过分批进行反应动力学分析进一步表征。通过合成8种不同的ACE抑制剂，以高达88％的产率和在≈0.5g h-1的通量范围内生产，证明了三步连续过程，同时避免了反应性中间体的分离和过程密集的反应条件。通过在工业相关的流动平台上制备世界卫生组织（WHO）的基本药物依那普利，进一步开发了该工艺，该平台将通量提高至≈1g h-1。
• L-Alanyl-N-(indan-2-yl)glycine, its esters and salts thereof
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04474692A1

  公开（公告）日：1984-10-02

  Useful intermediates for the preparation of hypotensives and inhibitors of angiotensin converting enzymes are L-alanyl-N-(indan-2-yl)glycine, its lower alkyl esters and the salts thereof.

  L-丙氨酸-N-(茚-2-基)甘氨酸及其较低的烷基酯和盐是制备降压药和血管紧张素转换酶抑制剂的有用中间体。
• Bicycle compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04822818A1

  公开（公告）日：1989-04-18

  New bicyclic compounds, inclusive of salts thereof, of the formula: ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and each represents hydrogen, hydroxyl or lower alkoxy, R.sup.3 is hydrogen or lower alkyl, R.sup.4 is hydrogen, lower alkyl, amino-lower-alkyl or acylamino-lower-alkyl, R.sup.5 is hydrogen, lower alkyl or aralkyl which may be substituted, R.sup.6 is hydroxyl, lower alkoxy, amino or lower alkylamino, and m and n each means 1 or 2, have inhibitory activities of angiotensin converting enzyme and bradykinin decomposing enzyme, and are useful as antihypertensive agents.

  新的双环化合物，包括其盐，化学式如下：##STR1## 其中，R.sup.1和R.sup.2相同或不同，分别代表氢、羟基或较低的烷氧基，R.sup.3代表氢或较低的烷基，R.sup.4代表氢、较低的烷基、氨基-较低-烷基或酰胺基-较低-烷基，R.sup.5代表氢、较低的烷基或可能被取代的芳基烷基，R.sup.6代表羟基、较低的烷氧基、氨基或较低的烷基氨基，m和n分别表示1或2，具有抑制血管紧张素转化酶和缓激肽降解酶的活性，并且可用作降压剂。
• N-substituted-amido-amino acids
  申请人：Rorer Pharmaceutical Corporation

  公开号：US04831184A1

  公开（公告）日：1989-05-16

  This invention relates to new chemical compounds having valuable pharmaceutical activity. It particularly relates to stereoisomeric compounds possessing hypotensive activity, i.e., angiotensin converting enzyme inhibitory (ACEI) activity and having the structure ##STR1## wherein R and R.sub.9 are independently hydroxy, lower alkoxy, lower alkenoxy, di(lower alkyl)amino-lower alkoxy, hydroxy-lower alkoxy, acylamino-lower alkoxy, acryloxy-lower alkoxy, aryloxy, aryloxyl-lower alkoxy, amino, lower alkylamino, di-lower alkylamino, hydroxyamino, or aryl-lower alkylamino; R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.7 and R.sub.8 are independently hydrogen, alkyl, alkenyl or alkynyl containing up to 20 carbon atoms, aryl or aryl-lower alkyl having from 7 to 12 carbon atoms, heterocyclic or heterocyclic-lower alkyl having from 6 to 12 carbon atoms, cycloalkyl or cycloalkyl-alkyl containing up to 20 carbon atoms in the cycloalkyl group, provided that each of R.sub.1 and R.sub.2 and R.sub.4 and R.sub.5 are different; R.sub.2 and R.sub.3 taken together with the carbon and nitrogen to which they are respectively attached and R.sub.3 and R.sub.5 taken together with the nitrogen and carbon to which they are respectively attached form an N-heterocycle containing from 3 to 5 carbon atoms or 2 to 4 carbon atoms and a sulfur atom; R.sub.6 is cycloalkyl, polycycloalkyl, partially saturated cycloalkyl and polycycloalkyl, cycloalkyl-lower alkyl, aryl, aryl-lower alkyl, aryl-lower alkenyl, aryl-lower alkynyl; and wherein each chiral center is in the (S) configuration; and salts thereof with acids or bases especially pharmaceutically acceptable acid and base salts.

  本发明涉及具有有价值的药物活性的新化学化合物。它特别涉及具有降压活性，即血管紧张素转化酶抑制剂（ACEI）活性的立体异构化合物，其结构为##STR1##其中R和R.sub.9独立地为羟基，较低的烷氧基，较低的烯氧基，二（较低烷基）氨基-较低烷氧基，羟基-较低烷氧基，酰胺基-较低烷氧基，丙烯氧基-较低烷氧基，芳基氧基，芳基氧基-较低烷氧基，氨基，较低烷基氨基，二-较低烷基氨基，羟基氨基或芳基-较低烷基氨基; R.sub.1，R.sub.2，R.sub.3，R.sub.4，R.sub.5，R.sub.7和R.sub.8独立地为氢，含有最多20个碳原子的烷基，烯基或炔基，含有从7到12个碳原子的芳基或芳基-较低烷基，含有从6到12个碳原子的杂环或杂环-较低烷基，含有最多20个碳原子的环烷基或环烷基-烷基，前提是R.sub.1和R.sub.2和R.sub.4和R.sub.5各不相同; R.sub.2和R.sub.3与它们分别附着的碳和氮以及R.sub.3和R.sub.5与它们分别附着的氮和碳一起形成含有3到5个碳原子或2到4个碳原子和一个硫原子的N-杂环; R.sub.6为环烷基，多环环烷基，部分饱和的环烷基和多环环烷基，环烷基-较低烷基，芳基，芳基-较低烷基，芳基-较低烯基或芳基-较低炔基; 其中每个手性中心都处于（S）构型; 以及与酸或碱的盐，特别是药学上可接受的酸和碱盐。