[Cyclohexyl-(3-mercapto-2-methyl-propionyl)-amino]-acetic acid | 78773-67-8

• 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: [Cyclohexyl-(3-mercapto-2-methyl-propionyl)-amino]-acetic acid
• 英文别名: N-(3-mercapto-2-methylpropanoyl)-N-cyclohexylglycine；2-[cyclohexyl-(2-methyl-3-sulfanylpropanoyl)amino]acetic acid
• CAS: 78773-67-8
• 化学式: C₁₂H₂₁NO₃S
• 分子量: 259.37
• InChiKey: FGFHICIYRMWGIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-cyclohexylglycine tert-butyl ester 在 碘代三甲硅烷 、 氨 、 水 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 19.42h， 生成 [Cyclohexyl-(3-mercapto-2-methyl-propionyl)-amino]-acetic acid
  参考文献：
  名称：

  Angiotensin-converting enzyme inhibitors. New orally active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives

  摘要：

  A variety of N-substituted (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives was synthesized and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) was examined in vitro and in vivo. The acylthio derivatives prepared are assumed to act as prodrugs since they are much less active than the corresponding free SH compounds in vitro and can be expected to act in vivo only after conversion to the free sulfhydryl compounds. A number of these compounds are potent ACE inhibitors that lowered blood pressure in Na-deficient, conscious spontaneously hypertensive rats (SHR), a high renin model. One of the most active members of the series was (S)-N-cyclopentyl-N-[3-[(2,2-dimethyl-1-oxopropyl)thio]-2-methyl-1 -oxopropyl]glycine (REV 3659-(S), pivopril). Structure-activity relationships are discussed.

  DOI：

  10.1021/jm00379a013

文献信息

• Angiotensin converting enzyme inhibitors: N-Substituted monocyclic and bicyclic amino acid derivatives
  作者：James L. Stanton、Norbert Gruenfeld、Joseph E. Babiarz、Michael H. Ackerman、Robert C. Friedmann、Andrew M. Yuan、William Macchia

  DOI：10.1021/jm00363a011

  日期：1983.9

  (14a-x),- N-arylalanines (15a,b),-N-cycloalkylglycines (16a-k), and -1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids (17a-d), -1,2,3,4-tetrahydroquinoline-2-carboxylic acids (18a-f), and -indoline-2-carboxylic acids (19a-k) is described. In vitro inhibition of angiotensin converting enzyme (ACE) is reported for each compound, and the structure--activity relationship for each series is discussed. The

  N-（3-巯基丙酰基）-N-芳基甘氨酸（14a-x），-N-芳基丙氨酸（15a，b），-N-环烷基甘氨酸（16a-k）和-1,2,3,4-的合成描述了四氢异喹啉-3-羧酸（17a-d），-1,2,3,4-四氢喹啉-2-羧酸（18a-f）和-二氢吲哚-2-羧酸（19a-k）。报道了每种化合物对血管紧张素转化酶（ACE）的体外抑制作用，并讨论了每个系列的结构-活性关系。讨论了ACE的体内抑制作用和各系列代表性化合物的降压作用。最有效的化合物19d的体外ACE IC50为2.6 X 10（-9）M，并且以10 mg / kg po的剂量在85 mm的自发性高血压大鼠中降低了血压。
• Antihypertensive amides
  申请人：USV Pharmaceutical Corporation

  公开号：US04256761A1

  公开（公告）日：1981-03-17

  Compounds of the structure: ##STR1## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 are hydrogen, alkyl, alkenyl, alkynyl, phenyl-alkyl, or cycloalkyl, n is an integer from 0 to 4 inclusive, M is alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, polycycloalkyl, polycyclo-alkyl-alkyl, aryl, aralkyl, heteroaryl, heteroaryl-alkyl, hetero-cycloalkyl, hetero-cycloalkyl-alkyl, alkoxyalkyl, alkylthioalkyl, alkylamino-alkyl, dialkylamino-alkyl, fused aryl-cycloalkyl, fused aryl-cycloalkyl-alkyl, fused heteroaryl-cycloalkyl, or fused heteroaryl-cycloalkyl-alkyl, Y is hydroxy, alkoxy, amino, or substituted amino, aminoalkanoyl, aryloxy, aminoalkoxy, or hydroxyalkoxy, and R.sub.7 is hydrogen, alkanoyl, carboxylalkanoyl, hydroxyalkanoyl, amino-alkanoyl, cyano, amidino, carbalkoxy, ZS, or ##STR2## wherein Z is hydrogen, alkyl, hyroxyalkyl, aminoalkyl or the radical ##STR3## wherein R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, n, M and Y are as described above; and where Y is hydroxy their non-toxic, pharmaceutically acceptable alkali metal, alkaline earth metal, and amine salts.

  结构式为：##STR1## 其中R.sub.1、R.sub.2、R.sub.3、R.sub.4、R.sub.5和R.sub.6均为氢、烷基、烯基、炔基、苯基烷基或环烷基，n为0至4的整数，M为烯基、炔基、环烷基、环烷基烷基、多环烷基、多环烷基烷基、芳基、芳基烷基、杂芳基、杂芳基烷基、杂环烷基、杂环烷基烷基、烷氧基烷基、烷硫基烷基、烷基氨基烷基、二烷基氨基烷基、融合芳基环烷基、融合芳基环烷基烷基、融合杂芳基环烷基或融合杂芳基环烷基烷基，Y为羟基、烷氧基、氨基或取代氨基、氨基酰基、芳氧基、氨基烷氧基或羟基烷氧基，R.sub.7为氢、脂肪酰基、羧基脂肪酰基、羟基脂肪酰基、氨基-脂肪酰基、氰基、胍基、羧烷氧基或##STR2## 其中Z为氢、烷基、羟基烷基、氨基烷基或基团##STR3## 其中R.sub.1、R.sub.2、R.sub.3、R.sub.4、R.sub.5、R.sub.6、n、M和Y如上所述；当Y为羟基时，它们为非毒性、药学上可接受的碱金属、碱土金属和胺盐。
• US4256761A
  申请人：——

  公开号：US4256761A

  公开（公告）日：1981-03-17
• Angiotensin-converting enzyme inhibitors. New orally active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives
  作者：John T. Suh、Jerry W. Skiles、Bruce E. Williams、Raymond D. Youssefyeh、Howard Jones、Bernard Loev、Edward S. Neiss、Alfred Schwab、William S. Mann

  DOI：10.1021/jm00379a013

  日期：1985.1

  A variety of N-substituted (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives was synthesized and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) was examined in vitro and in vivo. The acylthio derivatives prepared are assumed to act as prodrugs since they are much less active than the corresponding free SH compounds in vitro and can be expected to act in vivo only after conversion to the free sulfhydryl compounds. A number of these compounds are potent ACE inhibitors that lowered blood pressure in Na-deficient, conscious spontaneously hypertensive rats (SHR), a high renin model. One of the most active members of the series was (S)-N-cyclopentyl-N-[3-[(2,2-dimethyl-1-oxopropyl)thio]-2-methyl-1 -oxopropyl]glycine (REV 3659-(S), pivopril). Structure-activity relationships are discussed.