2,3-dihydro-1-(2-methyl-1-oxo-2-propenyl)-1H-indole-2-carboxylic acid dicyclohexylamine salt | 78701-41-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2,3-dihydro-1-(2-methyl-1-oxo-2-propenyl)-1H-indole-2-carboxylic acid dicyclohexylamine salt
• 英文别名: 2,3-dihydro-1-(2-methyl-1-oxo-2-propenyl)-IH-indole-2-carboxylic acid dicyclohexylamine salt；N-cyclohexylcyclohexanamine;1-(2-methylprop-2-enoyl)-2,3-dihydroindole-2-carboxylic acid
• CAS: 78701-41-4
• 化学式: C₁₂H₂₃N*C₁₃H₁₃NO₃
• 分子量: 412.572
• InChiKey: HOZWOJOVDLTNHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.85
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,3-dihydro-1-(2-methyl-1-oxo-2-propenyl)-1H-indole-2-carboxylic acid dicyclohexylamine salt 、 potassium hydrogensulfate 以52%的产率得到
  参考文献：
  名称：

  KIM, D. H.;GUINOSSO, CH. J.;BUZBY, G. C. ,, JR;HERBST, D. R.;MCCAULLY, R.+, J. MED. CHEM., 1983, 26, N 3, 394-403

  摘要：

  DOI：
• 作为产物：
  描述：

  2,3-dihydro-1-(2-methyl-1-oxo-2-propenyl)-1H-indole-2-carboxylic acid ethyl ester 、 氢氧化钾 以52%的产率得到
  参考文献：
  名称：

  KIM, D. H.;GUINOSSO, CH. J.;BUZBY, G. C. ,, JR;HERBST, D. R.;MCCAULLY, R.+, J. MED. CHEM., 1983, 26, N 3, 394-403

  摘要：

  DOI：

文献信息

• 10,10a-Dihydro-1H-thiozino[4,3-a,]-indole-1,4(3H)-diones
  申请人：American Home Products Corporation

  公开号：US04385180A1

  公开（公告）日：1983-05-24

  Disclosed herein are N-(3-mercapto-2-alkyl-1-oxopropyl)-2,5-dihydro-1H-indole-2-carboxylic acids and derivatives thereof which act as inhibitors of angiotensin converting enzyme and as anti-hypertensive agents. Derivatives include those in which the 5-mercapto group is substituted with phosphate derivatives or is replaced by a variously substituted amino group. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0; R.sub.1 is hydrogen, lower alkyl, aryl or aralkyl; R.sub.2 is hydrogen or lower alkyl; R.sub.3 is hydrogen, lower alkyl or aroyl; R.sub.5 is hydroxy, amino, or lower alkoxy; X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen; Y is hydrogen, lower alkyl, or aryl; R.sub.4 is --SH, ##STR2## wherein L is O, NR.sub.7 or S (where R.sub.7 is hydrogen or lower alkyl); M is R.sub.8, OR.sub.8, SR.sub.8, or NR.sub.9 R.sub.10 (where R.sub.8 is hydrogen, lower alkyl, aryl, or aralkyl; and R.sub.9 and R.sub.10 are, independently, hydrogen, lower alkyl, or aryl); A is O, NR.sub.15 or S; R.sub.11 and R.sub.12 are, independently, hydrogen, alkyl, aralkyl or aryl; R.sub.13 is hydrogen or lower alkyl; m is 0, 1, 2, or 3; R.sub.20 is hydrogen or aryl; and R.sub.21 is hydroxy or lower alkoxy; or pharmaceutically acceptable salts thereof.

  本发明涉及N-(3-巯基-2-烷基-1-氧代丙基)-2,5-二氢-1H-吲哚-2-羧酸及其衍生物，其作为血管紧张素转化酶抑制剂和降压剂。衍生物包括5-巯基基团被磷酸衍生物取代或被不同取代的氨基基团取代的化合物。本发明的化合物（不包括已公开的中间体）具有以下通式：##STR1## 其中：n为1或0；R.sub.1为氢、低碳基、芳基或芳基烷基；R.sub.2为氢或低碳基；R.sub.3为氢、低碳基或芳基酰基；R.sub.5为羟基、氨基或低烷氧基；X为氢、羟基、低碳基、低烷氧基或卤素；Y为氢、低碳基或芳基；R.sub.4为--SH、##STR2## 其中L为O、NR.sub.7或S（其中R.sub.7为氢或低碳基）；M为R.sub.8、OR.sub.8、SR.sub.8或NR.sub.9R.sub.10（其中R.sub.8为氢、低碳基、芳基或芳基烷基；R.sub.9和R.sub.10独立地为氢、低碳基或芳基）；A为O、NR.sub.15或S；R.sub.11和R.sub.12独立地为氢、烷基、芳基烷基或芳基；R.sub.13为氢或低碳基；m为0、1、2或3；R.sub.20为氢或芳基；R.sub.21为羟基或低烷氧基；或其药学上可接受的盐。
• 1,1'-[Dithiobis(2-alkyl-1-oxo-3,1-propanediyl)]-bis[2,3-dihydro-1H-indole
  申请人：American Home Products Corporation

  公开号：US04396773A1

  公开（公告）日：1983-08-02

  Disclosed herein are N-(3-mercapto-2-alkyl-1-oxopropyl)-2,3-dihydro-1H-indole-2-carboxylic acids and derivatives thereof which act as inhibitors of angiotensin converting enzyme and as anti-hypertensive agents. Derivatives include those in which the 3-mercapto group is substituted with phosphate derivatives or is replaced by a variously substituted amino group. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0; R.sub.1 is hydrogen, lower alkyl, aryl or aralkyl; R.sub.2 is hydrogen or lower alkyl; R.sub.3 is hydrogen, lower alkyl or aroyl; R.sub.5 is hydroxy, amino, or lower alkoxy; X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen; Y is hydrogen, lower alkyl, or aryl; R.sub.4 is -SH, ##STR2## wherein L is O, NR.sub.7 or S (where R.sub.7 is hydrogen or lower alkyl); M is R.sub.8, OR.sub.8, SR.sub.8, or NR.sub.9 R.sub.10 (where R.sub.8 is hydrogen, lower alkyl, aryl, or aralkyl; and R.sub.9 and R.sub.10 are, independently, hydrogen, lower alkyl, or aryl); A is O, NR.sub.13 or S; R.sub.11 and R.sub.12 are, independently, hydrogen, alkyl, aralkyl or aryl; R.sub.13 is hydrogen or lower alkyl; m is 0, 1, 2, or 3; R.sub.20 is hydrogen or aryl; and R.sub.21 is hydroxy or lower alkoxy; or pharmaceutically acceptable salts thereof.

  本文披露了N-(3-巯基-2-烷基-1-氧代丙基)-2,3-二氢-1H-吲哚-2-羧酸及其衍生物，其作为血管紧张素转化酶的抑制剂和降压剂。衍生物包括将3-巯基基团用磷酸盐衍生物替代或用各种取代氨基基团替换的化合物。本发明的化合物（不包括已披露的中间体）具有以下一般式：##STR1## 其中：n为1或0；R.sub.1为氢、较低的烷基、芳基或芳基烷基；R.sub.2为氢或较低的烷基；R.sub.3为氢、较低的烷基或芳基酰基；R.sub.5为羟基、氨基或较低的烷氧基；X为氢、羟基、较低的烷基、较低的烷氧基或卤素；Y为氢、较低的烷基或芳基；R.sub.4为-SH、##STR2## 其中L为O、NR.sub.7或S（其中R.sub.7为氢或较低的烷基）；M为R.sub.8、OR.sub.8、SR.sub.8或NR.sub.9R.sub.10（其中R.sub.8为氢、较低的烷基、芳基或芳基烷基；R.sub.9和R.sub.10独立地为氢、较低的烷基或芳基）；A为O、NR.sub.13或S；R.sub.11和R.sub.12独立地为氢、烷基、芳基烷基或芳基；R.sub.13为氢或较低的烷基；m为0、1、2或3；R.sub.20为氢或芳基；R.sub.21为羟基或较低的烷氧基；或其药学上可接受的盐。
• N-(2-Substituted-1-oxoalkyl)-2,3-dihydro-1H-indole-2-carboxylic acid
  申请人：American Home Products Corporation

  公开号：US04454291A1

  公开（公告）日：1984-06-12

  Disclosed herein are 2,3-dihydro-1H-indole-2-carboxylic acids substituted on the nitrogen with 3-mercapto-2-alkyl-1-oxoalkyl, 3-phosphoryl-2-alkyl-1-oxopropyl, or 2-amino-2-alkyl-1-oxoalkyl derivatives which act as inhibitors of angiotensin converting enzyme and as antihypertensive agents. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0; R.sub.1 is hydrogen, lower alkyl, aryl or aralkyl; R.sub.2 is hydrogen or lower alkyl; R.sub.3 is hydrogen, lower alkyl or aroyl; R.sub.5 is hydroxy, amino, or lower alkoxy; X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen; Y is hydrogen, lower alkyl, or aryl; Y is hydrogen, lower alkyl, or aryl; R.sub.4 is ##STR2## wherein: L is O, NR.sub.7 or S (where R.sub.7 is hydrogen or lower alkyl); M is R.sub.8, OR.sub.8, SR.sub.8, or NR.sub.9 R.sub.10 (where R.sub.8 is hydrogen, lower alkyl, aryl, or aralkyl; and R.sub.9 and R.sub.10 are, independently, hydrogen, lower alkyl, or aryl); A is O, NR.sub.13 or S; R.sub.11 and R.sub.12 are, independently, hydrogen, alkyl, aralkylor aryl; R.sub.13 is hydrogen or lower alkyl; m is 0, 1, 2, or 3; R.sub.20 is hydrogen or aryl; and R.sub.21 is hydroxy or lower alkoxy; or pharmaceutically acceptable salts thereof. Claimed compounds are intermediates of the formula: ##STR3## wherein R.sub.13 is hydrogen or lower alkyl; R.sub.14 is R.sub.5 or OZ, where R.sub.5 is hydroxy, amino, or lower alkoxy, and Z is a carboxylic acid protecting group.

  本文披露了在氮上以3-巯基-2-烷基-1-氧代烷基、3-磷酸基-2-烷基-1-氧代丙基或2-氨基-2-烷基-1-氧代烷基衍生物取代的2,3-二氢-1H-吲哚-2-羧酸，其作为血管紧张素转化酶抑制剂和降压剂。本发明化合物（不包括已披露的中间体）的一般式为：##STR1## 其中：n为1或0；R.sub.1为氢、低级烷基、芳基或芳基烷基；R.sub.2为氢或低级烷基；R.sub.3为氢、低级烷基或芳酰基；R.sub.5为羟基、氨基或低级烷氧基；X为氢、羟基、低级烷基、低级烷氧基或卤素；Y为氢、低级烷基或芳基；R.sub.4为##STR2## 其中：L为O、NR.sub.7或S（其中R.sub.7为氢或低级烷基）；M为R.sub.8、OR.sub.8、SR.sub.8或NR.sub.9R.sub.10（其中R.sub.8为氢、低级烷基、芳基或芳基烷基；R.sub.9和R.sub.10独立地为氢、低级烷基或芳基）；A为O、NR.sub.13或S；R.sub.11和R.sub.12独立地为氢、烷基、芳基烷基或芳基；R.sub.13为氢或低级烷基；m为0、1、2或3；R.sub.20为氢或芳基；R.sub.21为羟基或低级烷氧基；或其药学上可接受的盐。所述的化合物是以下中间体的中间体：##STR3## 其中R.sub.13为氢或低级烷基；R.sub.14为R.sub.5或OZ，其中R.sub.5为羟基、氨基或低级烷氧基，Z为羧酸保护基。
• N-[2-Substituted-1-oxoalkyl]-2,3-dihydro-1H-indole-2-carboxylic acid
  申请人：American Home Products Corporation

  公开号：US04454292A1

  公开（公告）日：1984-06-12

  Disclosed herein are 2,3-dihydro-1H-indole-2-carboxylic acids substitued on the nitrogen with 3-mercapto-2-alkyl-1-oxoalkyl, 3-phosphoryl-2-alkyl-1-oxopropyl, or 2-amino-2-alkyl-1-oxoalkyl derivatives which act as inhibitors of angiotensin converting enzyme and as antihypertensive agents. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0; R.sub.1 is hydrogen, lower alkyl, aryl or aralkyl; R.sub.2 is hydrogen or lower alkyl; R.sub.3 is hydrogen, lower alkyl or aroyl; R.sub.5 is hydroxy, amino, or lower alkoxy; X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen; Y is hydrogen, lower alkyl, or aryl; Y is hydrogen, lower alkyl, or aryl; R.sub.4 is ##STR2## wherein: L is O, NR.sub.7 or S (where R.sub.7 is hydrogen or lower alkyl); M is R.sub.8, OR.sub.8, SR.sub.8, or NR.sub.9 R.sub.10 (where R.sub.8 is hydrogen, lower alkyl, aryl, or aralkyl; and R.sub.9 and R.sub.10 are, independently, hydrogen, lower alkyl, or aryl); A is O, NR.sub.13 or S; R.sub.11 and R.sub.12 are, independently, hydrogen, alkyl, aralkylor aryl; R.sub.13 is hydrogen or lower alkyl; m is 0, 1, 2, or 3; R.sub.20 is hydrogen or aryl; and R.sub.21 is hydroxy or lower alkoxy; or pharmaceutically acceptable salts thereof. Claimed compounds are intermediates of the formula: ##STR3## wherein R.sub.15 is hydrogen or lower alkyl.

  本文披露了一种以3-巯基-2-烷基-1-氧代烷基、3-磷酸-2-烷基-1-氧代丙基或2-氨基-2-烷基-1-氧代烷基衍生物取代氮的2,3-二氢-1H-吲哚-2-羧酸，其作为血管紧张素转换酶抑制剂和降压剂。该发明化合物（不包括披露的中间体）的一般式如下：##STR1## 其中：n为1或0；R.sub.1为氢、低级烷基、芳基或芳烷基；R.sub.2为氢或低级烷基；R.sub.3为氢、低级烷基或芳酰基；R.sub.5为羟基、氨基或低级烷氧基；X为氢、羟基、低级烷基、低级烷氧基或卤素；Y为氢、低级烷基或芳基；R.sub.4为##STR2## 其中：L为O、NR.sub.7或S（其中R.sub.7为氢或低级烷基）；M为R.sub.8、OR.sub.8、SR.sub.8或NR.sub.9 R.sub.10（其中R.sub.8为氢、低级烷基、芳基或芳烷基；R.sub.9和R.sub.10独立地为氢、低级烷基或芳基）；A为O、NR.sub.13或S；R.sub.11和R.sub.12独立地为氢、烷基、芳烷基或芳基；R.sub.13为氢或低级烷基；m为0、1、2或3；R.sub.20为氢或芳基；R.sub.21为羟基或低级烷氧基；或其药学上可接受的盐。所述的化合物是以下中间体：##STR3## 其中R.sub.15为氢或低级烷基。
• 1H,5H-[1,4]Thiazepino[4,3-a]indole-1,5-diones
  申请人：American Home Products Corporation

  公开号：US04303583A1

  公开（公告）日：1981-12-01

  Disclosed herein are N-(3-mercapto-2-alkyl-1-oxopropyl)-2,3-dihydro-1H-indole-2-carboxylic acids and derivatives thereof which act as inhibitors of angiotensin converting enzyme and as anti-hypertensive agents. Derivatives include those in which the 3-mercapto group is substituted with phosphate derivatives or is replaced by a variously substituted amino group. The compounds of the invention (excluding disclosed intermediates) have the general formula: ##STR1## wherein: n is 1 or 0; R.sub.1 is hydrogen, lower alkyl, aryl or aralkyl; R.sub.2 is hydrogen or lower alkyl; R.sub.3 is hydrogen, lower alkyl or aroyl; R.sub.5 is hydroxy, amino, or lower alkoxy; X is hydrogen, hydroxy, lower alkyl, lower alkoxy, or halogen; Y is hydrogen, lower alkyl, or aryl; R.sub.4 is --SH, ##STR2## wherein L is O, NR.sub.7 or S (where R.sub.7 is hydrogen or lower alkyl); M is R.sub.8, OR.sub.8, or NR.sub.9 R.sub.10 (where R.sub.8 is hydrogen, lower alkyl, aryl, or aralkyl; and R.sub.9 and R.sub.10 are, independently, hydrogen, lower alkyl, or aryl); A is O, NR.sub.13 or S; R.sub.11 and R.sub.12 are, independently, hydrogen, alkyl, aralkyl or aryl; R.sub.13 is hydrogen or lower alkyl; m is 0, 1, 2, or 3; R.sub.20 is hydrogen or aryl; and R.sub.21 is hydroxy or lower alkoxy; or pharmaceutically acceptable salts thereof.

  本发明涉及N-(3-巯基-2-烷基-1-氧代丙基)-2,3-二氢-1H吲哚-2-羧酸及其衍生物，它们作为血管紧张素转化酶的抑制剂和抗高血压药物。衍生物包括3-巯基基团被磷酸盐衍生物取代或被各种取代的氨基基团所取代的衍生物。本发明化合物（不包括已披露的中间体）具有以下通式：##STR1##其中：n为1或0；R.sub.1为氢、低级烷基、芳基或芳基烷基；R.sub.2为氢或低级烷基；R.sub.3为氢、低级烷基或芳酰基；R.sub.5为羟基、氨基或低级烷氧基；X为氢、羟基、低级烷基、低级烷氧基或卤素；Y为氢、低级烷基或芳基；R.sub.4为--SH、##STR2##其中L为O、NR.sub.7或S（其中R.sub.7为氢或低级烷基）；M为R.sub.8、OR.sub.8或NR.sub.9R.sub.10（其中R.sub.8为氢、低级烷基、芳基或芳基烷基；R.sub.9和R.sub.10独立地为氢、低级烷基或芳基）；A为O、NR.sub.13或S；R.sub.11和R.sub.12独立地为氢、烷基、芳基烷基或芳基；R.sub.13为氢或低级烷基；m为0、1、2或3；R.sub.20为氢或芳基；R.sub.21为羟基或低级烷氧基；或其药学上可接受的盐。