N-(3-mercapto-2-methyl propanoyl)-N-cyclopentyl glycine-t-butyl ester | 85101-34-4

• 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: N-(3-mercapto-2-methyl propanoyl)-N-cyclopentyl glycine-t-butyl ester
• 英文别名: N-(3-mercapto-2-methylpropanoyl)-N-cyclopentylglycine t-butyl ester；tert-butyl 2-[cyclopentyl-(2-methyl-3-sulfanylpropanoyl)amino]acetate
• CAS: 85101-34-4
• 化学式: C₁₅H₂₇NO₃S
• 分子量: 301.45
• InChiKey: QGOJRTMTQFHYOS-UHFFFAOYSA-N

物化性质

• 沸点：
  416.1±38.0 °C(Predicted)
• 密度：
  1.07±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(3-mercapto-2-methyl propanoyl)-N-cyclopentyl glycine-t-butyl ester 在 碘代三甲硅烷 、 水 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 生成 {Cyclopentyl-[3-(3,3-dimethyl-butyrylsulfanyl)-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
• 作为产物：
  描述：

  N-环戊基甘氨酸叔丁酯 在 氨 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 16.5h， 生成 N-(3-mercapto-2-methyl propanoyl)-N-cyclopentyl glycine-t-butyl ester
  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

• Compounds having angiotensin converting enzyme inhibitory activity and
  申请人：USV Pharmaceutical Corporation

  公开号：US04661515A1

  公开（公告）日：1987-04-28

  Novel compounds possessing both angiotensin enzyme inhibitory activity and diuretic activity are disclosed. The compounds are represented by the general formula ##STR1## in which X is ##STR2## in which 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, and cycloalkyl, and may be the same or different; n is an integer from 0 to 4 inclusive; M is alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, polycycloalkyl, polycycloalkyl-alkyl, aryl, aralkyl, heteroaryl, heteroaryl-alkyl, hetero-cyloalkyl, hetero-cycloalkyl-alkyl, fused aryl-cycloalkyl, fused aryl-cycloalkyl-alkyl, fused heteroaryl-cycloalkyl, fused heteroaryl-cycloalkyl-alkyl, alkoxyalkyl, alkylthioalkyl, alkylamino-alkyl, or dialkylaminoalkyl, or M and R.sub.6 taken together with the nitrogen to which M is bonded and the carbon to which R.sub.6 is bonded form a saturated unsubstituted heterocyclic group containing 3 or 4 ring carbon atoms; Y is hydroxy, alkoxy, amino, or substituted amino, aminoalkanoyl, aryloxy, aminoalkoxy, or hydroxyalkoxy; Z.sub.1 and Z.sub.2 each is a chemical bond, the group X.sub.3 --(CH.sub.2).sub.m, an amino acid group or the group X.sub.3 --(CH.sub.2).sub.m --X.sub.3 wherein X.sub.3 is oxygen, sulfur or NH and m is an integer from 0 to 4 inclusive; A and B each is the same as R.sub.1 or halogen, trifluoromethyl, OR.sub.1, NO.sub.2, NR.sub.1 R.sub.2, SO.sub.2 NH.sub.2, CN, SR.sub.1, SOR.sub.1, SO.sub.2 R.sub.1, CONR.sub.1 R.sub.2, COOR.sub.1 ; C is hydrogen alkyl, heteroallyl, amino, --CR.sub.1 .dbd.CR.sub.2 --, ##STR3## aminoalkyl, furfurylmethylamino, aminoaryl or aminobenzyl; X.sub.1 and X.sub.2 are each S, SO, SO.sub.2, NR.sub.1, O, chemical bond, (CR.sub.9 R.sub.10).sub.m, --CR.sub.9 .dbd.CR.sub.10 --, and CHOH, with the proviso that at least one of X.sub.1 and X.sub.2 be (CR.sub.9 R.sub.10).sub.m, wherein R.sub.9 and R.sub.10 are each hydrogen or lower alkyl, and m is an integer from 1 to 5; Ar is a divalent arylene or heteroarylene; and R.sub.7 and R.sub.8 are each hydrogen, alkyl, halo, cyano, hydroxy, alkoxy, amino, alkylamino, dialkylamino, mercapto, alkylmercapto, nitro, trifluoromethyl, carboxy, carbalkoxy, COY and NHCONHR.sub.1 wherein R.sub.1 and Y are as hereindefined; and pharmaceutically-acceptable salts thereof.

  本发明揭示了一种同时具有血管紧张素酶抑制活性和利尿活性的新型化合物。该化合物由一般式##STR1##表示，其中X是##STR2##其中R.sub.1、R.sub.2、R.sub.3、R.sub.4、R.sub.5和R.sub.6是氢、烷基、烯基、炔基、苯基-烷基和环烷基，可以相同也可以不同；n是0到4的整数；M是烯基、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、融合芳基-环烷基、融合芳基-环烷基-烷基、融合杂芳基-环烷基、融合杂芳基-环烷基-烷基、烷氧基烷基、烷硫基烷基、烷基氨基-烷基或二烷基氨基烷基，或M和R.sub.6与M键结的氮和R.sub.6键结的碳形成一个饱和未取代的含有3或4个环碳原子的杂环基；Y是羟基、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；Z.sub.1和Z.sub.2分别是化学键、X.sub.3--(CH.sub.2).sub.m、氨基酸基团或X.sub.3--(CH.sub.2).sub.m--X.sub.3，其中X.sub.3是氧、硫或NH，m是0到4的整数；A和B分别与R.sub.1相同或是卤素、三氟甲基、OR.sub.1、NO.sub.2、NR.sub.1 R.sub.2、SO.sub.2 NH.sub.2、CN、SR.sub.1、SOR.sub.1、SO.sub.2 R.sub.1、CONR.sub.1 R.sub.2、COOR.sub.1；C是氢烷基、杂烯基、氨基、--CR.sub.1.dbd.CR.sub.2--、##STR3##氨基烷基、呋喃甲基氨基、氨基芳基或氨基苯基；X.sub.1和X.sub.2分别是S、SO、SO.sub.2、NR.sub.1、O、化学键、(CR.sub.9 R.sub.10).sub.m、--CR.sub.9.dbd.CR.sub.10--和CHOH，但至少有一个X.sub.1和X.sub.2是(CR.sub.9 R.sub.10).sub.m，其中R.sub.9和R.sub.10分别是氢或低烷基，m是1到5的整数；Ar是二价芳基或杂芳基；R.sub.7和R.sub.8分别是氢、烷基、卤素、氰基、羟基、烷氧基、氨基、烷基氨基、二烷基氨基、巯基、烷基巯基、硝基、三氟甲基、羧基、羧基烷氧基、COY和NHCONHR.sub.1，其中R.sub.1和Y如上所定义；以及其药学上可接受的盐。
• Antihypertensive compounds
  申请人：USV Pharmaceutical Corporation

  公开号：US04507316A1

  公开（公告）日：1985-03-26

  Provided are antihypertensive compounds of the formula ##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, and may be the same or different, m is an integer from 0 to 2 inclusive, n is an integer from 0 to 4 inclusive, M is alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, polycycloalkyl, polycycloalkyl-alkyl, aryl, aralkyl, heteroaryl, heteroaryl-alkyl, hetero-cycloalkyl, hetero-cycloalkyl-alkyl, fused aryl-cycloalkyl, fused aryl-cycloalkyl-alkyl, fused heteroaryl-cycloalkyl, fused heteroaryl-cycloalkyl-alkyl, alkoxyalkyl, alkylthioalkyl, alkylamino-alkyl, or dialkylaminoalkyl. Y is hydroxy, alkoxy, amino, or substituted amino, aminoalkanoyl, aryloxy, aminoalkoxy, or hydroxyalkoxy, and R.sub.7 is alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclic, ##STR2## wherein R is hydrogen, alkyl, or aryl, and where Y is hydroxy, their pharmaceutically acceptable, nontoxic alkali metal, alkaline earth metal, and amine salts.

  提供了以下化学式的降压化合物：##STR1## 其中R.sub.1，R.sub.2，R.sub.3，R.sub.4，R.sub.5和R.sub.6为氢，烷基，烯基，炔基，苯基-烷基或环烷基，可以相同或不同，m是0到2的整数，n是0到4的整数，M是烯基，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，杂环芳基，杂环芳基-烷基，杂环环烷基，杂环环烷基-烷基，融合芳基-环烷基，融合芳基-环烷基-烷基，融合杂环芳基-环烷基，融合杂环芳基-环烷基-烷基，烷氧基烷基，烷硫基烷基，烷基氨基烷基或二烷基氨基烷基。Y是羟基，烷氧基，氨基或取代氨基，氨基烷酰基，芳氧基，氨基烷氧基或羟基烷氧基，R.sub.7是烷基，芳基，芳基-烷基，环烷基，环烷基-烷基，杂环，##STR2##其中R为氢，烷基或芳基，Y为羟基，它们的药学上可接受，无毒的碱金属，碱土金属和胺盐。
• Antihypertensive amide compounds
  申请人：Rorer Pharmaceutical Corporation

  公开号：US04839367A1

  公开（公告）日：1989-06-13

  Provided are antihypertensive compounds of the formula ##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, and may be the same or different, m is an integer from 0 to 2 inclusive, n is an integer from 0 to 4 inclusive, M is alkyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, polycycloalkyl, polycycloalkyl-alkyl, aryl, aralkyl, heteroaryl, heteroaryl-alkyl, hetero-cycloalkyl, hetero-cycloalkyl-alkyl, fused aryl-cycloalkyl, fused aryl-cycloalkyl-alkyl, fused heteroaryl-cycloalkyl, fused heteroaryl-cycloalkyl-alkyl, alkoxyalkyl, alkylthioalkyl, alkylamino-alkyl, or dialkylaminoalkyl, Y is hydroxy, alkoxy, amino, or substituted amino, aminoalkanoyl, aryloxy, aminoalkoxy, or hydroxyalkoxy, and R.sub.7 is alkyl, aryl, aralkyl, cycloalkyl, cycloalkyl-alkyl, heterocyclic, --CO--SR, --CS--SR, ##STR2## CH.sub.2 CO.sub.R, --CHM--CO.sub.2 R, --CH.sub.2 --CO--SR, --CN, ##STR3## --CO--NH--CH.sub.2 CO.sub.2 R, ##STR4## or --CO--CO.sub.2 CO.sub.2 R, wherein R is hydrogen, alkyl, or aryl, and where Y is hydroxy, their pharmaceutically acceptable, nontoxic alkali metal, alkaline earth metal, and amine salts.

  提供的是抗高血压化合物的公式，其中R.sub.1，R.sub.2，R.sub.3，R.sub.4，R.sub.5和R.sub.6为氢，烷基，烯基，炔基，苯基-烷基或环烷基，可以相同或不同，m为0到2的整数，n为0到4的整数，M为烷基，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，杂环芳基，杂环芳基-烷基，杂环环烷基，杂环环烷基-烷基，融合芳基-环烷基，融合芳基-环烷基-烷基，融合杂环芳基-环烷基，融合杂环芳基-环烷基-烷基，烷氧基烷基，烷硫基烷基，烷基氨基烷基或二烷基氨基烷基，Y为羟基，烷氧基，氨基或取代氨基，氨基烷酰基，芳氧基，氨基烷氧基或羟基烷氧基，R.sub.7为烷基，芳基，芳基-烷基，环烷基，环烷基-烷基，杂环，--CO--SR，--CS--SR，##STR2## CH.sub.2 CO.sub.R，--CHM--CO.sub.2 R，--CH.sub.2 --CO--SR，--CN，##STR3## --CO--NH--CH.sub.2 CO.sub.2 R，##STR4## 或--CO--CO.sub.2 CO.sub.2 R，其中R为氢，烷基或芳基，且当Y为羟基时，它们的药学上可接受，无毒的碱金属，碱土金属和胺盐。
• Mercapto amino acids, process for their preparation and pharmaceutical compositions containing them
  申请人：USV PHARMACEUTICAL CORPORATION

  公开号：EP0066254B1

  公开（公告）日：1987-02-04
• Compounds having angiotensin converting enzyme inhibitory activity and diuretic activity
  申请人：RORER INTERNATIONAL (OVERSEAS) INC.

  公开号：EP0100053B1

  公开（公告）日：1987-10-21