2,3-dihydro-5-methoxy-1-(2-methyl-1-oxo-2-propenyl)-1H-indole-2-carboxylic acid | 78701-44-7

• 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-5-methoxy-1-(2-methyl-1-oxo-2-propenyl)-1H-indole-2-carboxylic acid
• 英文别名: 5-Methoxy-1-(2-methyl-acryloyl)-2,3-dihydro-1H-indole-2-carboxylic acid；5-methoxy-1-(2-methylprop-2-enoyl)-2,3-dihydroindole-2-carboxylic acid
• CAS: 78701-44-7
• 化学式: C₁₄H₁₅NO₄
• 分子量: 261.277
• InChiKey: SZNDXYWHBVPHMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  硫代苯甲酸 、 2,3-dihydro-5-methoxy-1-(2-methyl-1-oxo-2-propenyl)-1H-indole-2-carboxylic acid 在 4-二甲氨基吡啶 作用下， 以 丙酮 为溶剂， 反应 6.0h， 以13%的产率得到(2S)-1-[(2S)-3-benzoylsulfanyl-2-methylpropanoyl]-5-methoxy-2,3-dihydroindole-2-carboxylic acid
  参考文献：
  名称：

  （巯基丙酰基）二氢吲哚-2-羧酸和相关化合物作为有效的血管紧张素转化酶抑制剂和降压药。

  摘要：

  合成了1-（3-巯基-2-甲基-1-氧丙基）二氢吲哚-2-羧酸（7b）及其相关化合物，以检测其抑制血管紧张素转化酶（ACE）和降低收缩压的能力自发性高血压大鼠（SHR）。前体1- [3-（苯甲硫基）-2-甲基-1-氧丙基]二氢吲哚-2-羧酸（6b）的所有四种可能的立体异构体均具有绝对立体化学特征。通过用2-甲氧基乙胺处理方便地除去前体的苯甲酰基以得到7b。苯甲酰基衍生物6的四个立体异构体中的三个以下列顺序显示了体外ACE抑制活性：6b（S，S）大于6b（S，R）大于6b（R，S）。具有R，R构型的立体异构体基本上是无活性的。用Et或OMe组取代吲哚核的C5处，仅引起抑制活性的微小变化。硫醇7b（S，S）是这项研究中合成的最具活性的ACE抑制剂，其体外效能是卡托普利的3倍。与卡托普利相比，效力的增强可能是由于7b（S，S）的疏水性增加，并表明在ACE的活性位点存在疏水口袋。在自发性高血压大鼠

  DOI：

  10.1021/jm00357a014
• 作为产物：
  描述：

  ethyl 5-methoxy-1-(2-methyl-1-oxo-2-propenyl)indoline-2-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 以77%的产率得到2,3-dihydro-5-methoxy-1-(2-methyl-1-oxo-2-propenyl)-1H-indole-2-carboxylic acid
  参考文献：
  名称：

  （巯基丙酰基）二氢吲哚-2-羧酸和相关化合物作为有效的血管紧张素转化酶抑制剂和降压药。

  摘要：

  合成了1-（3-巯基-2-甲基-1-氧丙基）二氢吲哚-2-羧酸（7b）及其相关化合物，以检测其抑制血管紧张素转化酶（ACE）和降低收缩压的能力自发性高血压大鼠（SHR）。前体1- [3-（苯甲硫基）-2-甲基-1-氧丙基]二氢吲哚-2-羧酸（6b）的所有四种可能的立体异构体均具有绝对立体化学特征。通过用2-甲氧基乙胺处理方便地除去前体的苯甲酰基以得到7b。苯甲酰基衍生物6的四个立体异构体中的三个以下列顺序显示了体外ACE抑制活性：6b（S，S）大于6b（S，R）大于6b（R，S）。具有R，R构型的立体异构体基本上是无活性的。用Et或OMe组取代吲哚核的C5处，仅引起抑制活性的微小变化。硫醇7b（S，S）是这项研究中合成的最具活性的ACE抑制剂，其体外效能是卡托普利的3倍。与卡托普利相比，效力的增强可能是由于7b（S，S）的疏水性增加，并表明在ACE的活性位点存在疏水口袋。在自发性高血压大鼠

  DOI：

  10.1021/jm00357a014

文献信息

• 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.

  本文揭示了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，其作为抑制血管紧张素转化酶和降压药物的作用。衍生物包括那些其中3-巯基团被磷酸衍生物取代或被各种取代的氨基团替换的化合物。发明的化合物（不包括已披露的中间体）具有以下通式： 其中：n为1或0；R.sub.1为氢、低烷基、芳基或芳基烷基；R.sub.2为氢或低烷基；R.sub.3为氢、低烷基或芳酰基；R.sub.5为羟基、氨基或低烷氧基；X为氢、羟基、低烷基、低烷氧基或卤素；Y为氢、低烷基或芳基；R.sub.4为-SH、 其中L为O、NR.sub.7或S（其中R.sub.7为氢或低烷基）；M为R.sub.8、OR.sub.8、SR.sub.8或NR.sub.9R.sub.10（其中R.sub.8为氢、低烷基、芳基或芳基烷基；R.sub.9和R.sub.10分别为氢、低烷基或芳基）；A为O、NR.sub.13或S；R.sub.11和R.sub.12分别为氢、烷基、芳基烷基或芳基；R.sub.13为氢或低烷基；m为0、1、2或3；R.sub.20为氢或芳基；R.sub.21为羟基或低烷氧基；或其药用盐。
• N-(2-Substituted-1-oxoalkyl)-2,3-dihydro-1H-indole-2-carboxylic acid
  申请人：American Home Products Corporation

  公开号：US04350633A1

  公开（公告）日：1982-09-21

  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, 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.

  本文披露了在氮上用3-巯基-2-烷基-1-氧代烷基、3-磷酰基-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，其作为抑制肾素转化酶和降压剂。发明的化合物（不包括披露的中间体）具有以下通用式：其中：n为1或0；R1为氢、低烷基、芳基或芳基烷基；R2为氢或低烷基；R3为氢、低烷基或芳酰基；R5为羟基、氨基或低烷氧基；X为氢、羟基、低烷基、低烷氧基或卤素；Y为氢、低烷基或芳基；R4为其中：L为O、NR7或S（其中R7为氢或低烷基）；M为R8、OR8、SR8或NR9R10（其中R8为氢、低烷基、芳基或芳基烷基；R9和R10分别为氢、低烷基或芳基）；A为O、NR13或S；R11和R12分别为氢、烷基、芳基烷基或芳基；R13为氢或低烷基；m为0、1、2或3；R20为氢或芳基；R21为羟基或低烷氧基；或其药用盐。
• 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，其作为抑制肾素转化酶和降压药物。衍生物包括那些其中3-巯基基团被磷酸酯衍生物取代或被各种取代的氨基团替换的化合物。发明的化合物（不包括披露的中间体）具有以下一般式：##STR1## 其中：n为1或0；R.sub.1为氢、低烷基、芳基或芳基烷基；R.sub.2为氢或低烷基；R.sub.3为氢、低烷基或芳酰基；R.sub.5为羟基、氨基或低烷氧基；X为氢、羟基、低烷基、低烷氧基或卤素；Y为氢、低烷基或芳基；R.sub.4为--SH，##STR2## 其中L为O、NR.sub.7或S（其中R.sub.7为氢或低烷基）；M为R.sub.8、OR.sub.8或NR.sub.9 R.sub.10（其中R.sub.8为氢、低烷基、芳基或芳基烷基；R.sub.9和R.sub.10分别为氢、低烷基或芳基）；A为O、NR.sub.13或S；R.sub.11和R.sub.12分别为氢、烷基、芳基烷基或芳基；R.sub.13为氢或低烷基；m为0、1、2或3；R.sub.20为氢或芳基；R.sub.21为羟基或低烷氧基；或其药用盐。
• 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。
• 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。