1-(N-(1-(乙氧羰基)-3-苯基丙基)-L-丙氨酰)-L-脯氨酸马来酸盐 | 82009-37-8

• 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
• 中文名称: 1-(N-(1-(乙氧羰基)-3-苯基丙基)-L-丙氨酰)-L-脯氨酸马来酸盐
• 英文名称: enalapril maleate
• 英文别名: N-[N-(1-S-Ethoxycarbonyl-3-phenylpropyl)-L-alanyl]-L-proline, maleate；N-(1-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline maleate salt；1-(N-(1-(Ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-L-proline maleate；(Z)-but-2-enedioic acid;(2S)-1-[(2S)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoyl]pyrrolidine-2-carboxylic acid
• CAS: 82009-37-8
• 化学式: C₄H₄O₄*C₂₀H₂₈N₂O₅
• 分子量: 492.526
• InChiKey: OYFJQPXVCSSHAI-DYAOETJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.32
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  171
• 氢给体数：
  4
• 氢受体数：
  10

文献信息

• Renin inhibitory peptides containing suleptanic acid or derivatives thereof
  申请人：THE UPJOHN COMPANY

  公开号：EP0355065A1

  公开（公告）日：1990-02-21

  The present invention provides novel renin-inhibiting peptides having a non-cleavable transition state insert corresponding to the 10,11- position of the renin substrate (angiotensinogen) and having a suleptanic acid moiety or derivatives thereof of the formula L₁ at the N-terminus of the peptide. Such inhibitors are useful for the diagnosis and control of renin-dependent hypertension, congestive heart failure, renin dependent hyperaldosterism, other renin depen­dent cardiovascular disorders and ocular disorders. Y₁0₃S-(CH₂)n-N(R₁)--(CH₂)q--      L₁

  本发明提供了一种新型的抑制肾素的肽，其具有对应于肾素底物（血管紧张素原）的10,11位的不可切割过渡态插入物，并在肽的N-末端具有苏力帕尼酸基团或其衍生物的L₁式。这种抑制剂对于诊断和控制肾素依赖性高血压、充血性心力衰竭、肾素依赖性高醛固酮症、其他肾素依赖性心血管疾病和眼部疾病非常有用。Y₁0₃S-(CH₂)n-N(R₁)--(CH₂)q--      L₁
• Process for preparing pharmacologically acceptable salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid
  申请人：Kaneka Corporation

  公开号：US20020087007A1

  公开（公告）日：2002-07-04

  There is provided a process for preparing a pharmacologically acceptable salt of N-( 1 (S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid which comprises condensing an amino acid and N-( 1 (S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine. N-carboxy-anhydride under basic condition, carrying out decarboxylation under between neutral and acidic condition to obtain N-( 1 (S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid, and forming a pharmacologically acceptable salt thereof, wherein the production of a by-product (3): 1 is suppressed by carrying out in an aqueous liquid a series of operations till formation of the pharmacologically acceptable salt or till isolation of the pharmacologically acceptable salt. The present invention enables to prepare the pharmacologically acceptable salt of N-( 1 (S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-amino acid having high quality, in a commercial scale with high yield and economical efficiency.

  提供了一种制备N-(1(S)-乙氧羰基-3-苯基丙基)-L-丙氨酸氨基酸药物可接受的盐的方法，其中包括在碱性条件下将氨基酸和N-(1(S)-乙氧羰基-3-苯基丙基)-L-丙氨酸-N-羧酸酐缩合，进行中性到酸性条件下的脱羧作用以获得N-(1(S)-乙氧羰基-3-苯基丙基)-L-丙氨酸氨基酸，并形成药物可接受的盐。通过在水液中进行一系列操作，直到形成药物可接受的盐或分离药物可接受的盐，抑制副产物(3)：1的产生。本发明能够在商业规模上高产率、高效率地制备高质量的N-(1(S)-乙氧羰基-3-苯基丙基)-L-丙氨酸氨基酸药物可接受的盐。
• Renin inhibitors containing histidine replacements
  申请人：Merck & Co., Inc.

  公开号：EP0273696A2

  公开（公告）日：1988-07-06

  Peptides of the formula: which comprises novel elements replacing the His(9) sequence in renin-inhibitory peptides based on substrate analogy, which have improved bioavailability and pharmacodynamic properties; compositions containing these renin-inhibitory peptides, optionally with other antihypertensive agents; and methods of treating hypertension or congestive heart failure or of establishing renin as a causative factor in these problems employing the novel peptides.

  该文描述了一种新的肽类分子，其公式为：其中替代了肾素抑制肽中亮氨酸（9）序列的新元素，基于底物类比，具有改善的生物利用度和药效学特性；包含这些肾素抑制肽的组合物，可选地与其他降压药物一起使用；以及使用这些新肽治疗高血压或充血性心力衰竭或确定肾素作为这些问题的致因因素的方法。
• Carboxyalkyl dipeptide derivatives, process for preparing them and pharmaceutical composition containing them
  申请人：Merck & Co., Inc.

  公开号：EP0012401A1

  公开（公告）日：1980-06-25

  Carboxyalkyl dipeptide derivatives and related compounds which are useful as antihypertensives, and having the formulae: wherein R and R6 are the same or different and are hydroxy, alkoxy, alkenoxy, dialkylamino alkoxy, acylamino alkoxy, acyloxy alkoxy, aryloxy, alkyloxy, substituted aryloxy or substituted aralkoxy wherein the substituent is methyl, halo, or niethoxy, amino, alkylamino, dialkylamino, aralkylamino or hydroxyamino; R1 is hydrogen, alkyl of from 1 to 20 carbon atoms, including branched, cyclic and unsaturated alkyl groups; substituted alkyl wherein the substituent is halo, hydroxy, alkoxy, aryloxy amino, alkylamino, dialkylamino, acylamino, arylamino, guanidino, imidazolyl, indolyl, mercapto, alkylthio, arylthio, carboxy, carboxamido, carbalkoxy, phenyl, substituted phenyl wherein the substituent is alkyl, alkoxy or halo; aralkyl or heteroaralkyl, aralkenyl or heteroaralkenyl, substituted aralkyl, substituted heteroaralkyl, substituted aralkenyl or substituted hetereoaralkenyl, wherein the substituent is halo or dihalo, alkyl, hydroxy, alkoxy, amino, aminomethyl, acylamino, dialkylamino, alkylamino, carboxyl, haloalkyl, cyano or sulfonamido, aralkyl or hetereoaralkyl substituted on the alkyl portion by amino or acylamino; R2 and R7 are hydrogen or alkyl; R3 is hydrogen, alkyl, phenylalkyl, aminomethylphenyl- alkyl, hydroxyphenylalkyl, hydroxyalkyl, acetylaminoalkyl, acylaminoalkyl, acylaminoalkyl aminoalkyl, dimethyl- aminoalkyl, haloalkyl, guanidinoalkyl, imidazolylalkyl, indolylalkyl, mercaptoalkyl and aikylthioalkyl; R4 is hydrogen or alkyl; R5 is hydrogen, alkyl, phenyl, phenylalkyl, hydroxyphenylalkyl, hydroxyalkyl, aminoalkyl, guanidinoalkyl, imidazolylalkyl, indolylalkyl, mercaptoalkyl or alkylthioalkyl; R and R5 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms, an alkylene bridge of from 2 to 3 carbon atoms and one sulphur atom, an alkylene bridge of from 3 to 4 carbon atoms containing a double bond or an alkylene bridge as above, substituted with hydroxy, alkoxy or alkyl and the pharmaceutically acceptable salts thereof.

  可用作抗高血压药的羧烷基二肽衍生物及相关化合物，其式如下 其中 R 和 R6 相同或不同，并且是羟基、烷氧基、烯氧基、二烷基氨基烷氧基、酰氨基烷氧基、酰氧基烷氧基、芳氧基、烷氧基、取代的芳氧基或取代的烷氧基，其中取代基是甲基、卤代或二乙氧基、氨基、烷基氨基、二烷基氨基、芳基氨基或羟基氨基； R1 是氢、1 至 20 个碳原子的烷基，包括支链、环状和不饱和烷基； 取代基为卤素、羟基、烷氧基、芳氧基氨基、烷基氨基、二烷基氨基、酰基氨基、芳基氨基、胍基、咪唑基、吲哚基、巯基、烷硫基、芳硫基、羧基、羧酰胺基、羰基烷氧基、苯基、取代基为烷基、烷氧基或卤素的取代苯基；芳烷基或杂烷基、芳烯基或杂芳烯基、取代的芳烷基、取代的杂烷基、取代的芳烯基或取代的对位芳烯基，其中取代基为卤代或二卤代、烷基、羟基、烷氧基、氨基、氨甲基、酰氨基、二烷基氨基、烷基氨基、羧基、卤代烷基、氰基或磺酰氨基，烷基部分被氨基或酰氨基取代的芳烷基或对位芳烷基； R2 和 R7 是氢或烷基； R3 是氢、烷基、苯基烷基、氨甲基苯基烷基、羟基苯基烷基、羟基烷基、乙酰氨基烷基、酰氨基烷基、酰氨基烷基氨基烷基、二甲基氨基烷基、卤代烷基、胍基烷基、咪唑基烷基、吲哚基烷基、巯基烷基和烷硫基烷基； R4 是氢或烷基 R5 是氢、烷基、苯基、苯基烷基、羟苯基烷基、羟基烷基、氨基烷基、胍基烷基、咪唑基烷基、吲哚基烷基、巯基烷基或硫代烷基； R 和 R5 可连接在一起，形成 2 至 4 个碳原子的亚烷基桥、2 至 3 个碳原子和一个硫原子的亚烷基桥、含有双键的 3 至 4 个碳原子的亚烷基桥或被羟基、烷氧基或烷基取代的上述亚烷基桥及其药学上可接受的盐。
• Antihypertensive composition
  申请人：Merck & Co., Inc.

  公开号：EP0129136A2

  公开（公告）日：1984-12-27

  A pharmaceutical composition is disclosed which comprises the combination of interphenylene 9-thia-11-oxo-12-aza prostanoic acid derivatives and carboxyalkyl dipeptide derivatives.

  本发明公开了一种药物组合物，它由间苯 9-硫杂-11-氧代-12-氮杂前列酸衍生物和羧烷基二肽衍生物组合而成。