3-amino-5-cyano-1,1-dimethylindane | 142559-86-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 3-amino-5-cyano-1,1-dimethylindane
• 英文别名: 3-Amino-1,1-dimethyl-2,3-dihydroindene-5-carbonitrile
• CAS: 142559-86-2
• 化学式: C₁₂H₁₄N₂
• 分子量: 186.257
• InChiKey: BNPSHNSBNQJROV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-amino-5-cyano-1,1-dimethylindane 、 N-cyano-N'-phenylthiourea sodium salt 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-Cyano-2-(6-cyano-3,3-dimethyl-1,2-dihydroinden-1-yl)-3-phenylguanidine
  参考文献：
  名称：

  Cardioselective Antiischemic ATP-Sensitive Potassium Channel Openers. 2. Structure-Activity Studies on Benzopyranylcyanoguanidines; Modification of the Benzopyran Ring

  摘要：

  The ATP-sensitive potassium channel (K-ATP) openers are of considerable interest as myocardial protecting agents. However, there exists a narrow window of safety for the use of first-generation compounds as antiischemic agents due to their powerful peripheral vasodilating effects, which can result in underperfusion of the area already at risk. We have recently disclosed the discovery of benzopyranylcyanoguanidine type K-ATP openers (BMS-180448) which are more selective for the ischemic myocardium compared to the first-generation compounds. This publication deals with structure-activity relationships for the antiischemic activity of the lead compound 8. The presence of an electron-withdrawing group at C6, an sp(3) center at C4, and a gem-dimethyl group at C2 appears to be essential for antiischemic activity. Cyanoguanidine can be replaced with a urea moiety. The results reported here support the hypothesis that distinct structure-activity relationships exist for antiischemic and vaso:relaxant activities of compounds related to 8 and cromakalim. The trifluoromethyl analog 10 is 550-fold more selective in vitro for the ischemic myocardium compared to the first-generation agent cromakalim. The reasons for the selectivity of these compounds for the ischemic myocardium are not clear at the present time. They may be related to the existence of receptor subtypes in smooth muscle and the myocardium.

  DOI：

  10.1021/jm00011a016
• 作为产物：
  描述：

  3-Azido-5-cyano-1,1-dimethylindane 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 生成 3-amino-5-cyano-1,1-dimethylindane
  参考文献：
  名称：

  Cardioselective Antiischemic ATP-Sensitive Potassium Channel Openers. 2. Structure-Activity Studies on Benzopyranylcyanoguanidines; Modification of the Benzopyran Ring

  摘要：

  The ATP-sensitive potassium channel (K-ATP) openers are of considerable interest as myocardial protecting agents. However, there exists a narrow window of safety for the use of first-generation compounds as antiischemic agents due to their powerful peripheral vasodilating effects, which can result in underperfusion of the area already at risk. We have recently disclosed the discovery of benzopyranylcyanoguanidine type K-ATP openers (BMS-180448) which are more selective for the ischemic myocardium compared to the first-generation compounds. This publication deals with structure-activity relationships for the antiischemic activity of the lead compound 8. The presence of an electron-withdrawing group at C6, an sp(3) center at C4, and a gem-dimethyl group at C2 appears to be essential for antiischemic activity. Cyanoguanidine can be replaced with a urea moiety. The results reported here support the hypothesis that distinct structure-activity relationships exist for antiischemic and vaso:relaxant activities of compounds related to 8 and cromakalim. The trifluoromethyl analog 10 is 550-fold more selective in vitro for the ischemic myocardium compared to the first-generation agent cromakalim. The reasons for the selectivity of these compounds for the ischemic myocardium are not clear at the present time. They may be related to the existence of receptor subtypes in smooth muscle and the myocardium.

  DOI：

  10.1021/jm00011a016

文献信息

• Indane and quinoline derivatives
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05401848A1

  公开（公告）日：1995-03-28

  Novel indane and quinoline derivatives, useful, for example, as antiischemic agents, having the formula ##STR1## where A, X, R.sub.1 -R.sub.7 are as defined herein, are disclosed.

  新的茚和喹啉衍生物，例如作为抗缺血药物有用，其化学式为##STR1##其中A、X、R.sub.1 -R.sub.7如本文所定义。
• US5401848A
  申请人：——

  公开号：US5401848A

  公开（公告）日：1995-03-28
• Cardioselective Antiischemic ATP-Sensitive Potassium Channel Openers. 2. Structure-Activity Studies on Benzopyranylcyanoguanidines; Modification of the Benzopyran Ring
  作者：Karnail S. Atwal、Gary J. Grover、Francis N. Ferrara、Syed Z. Ahmed、Paul G. Sleph、Steven Dzwonczyk、Diane E. Normandin

  DOI：10.1021/jm00011a016

  日期：1995.5

  The ATP-sensitive potassium channel (K-ATP) openers are of considerable interest as myocardial protecting agents. However, there exists a narrow window of safety for the use of first-generation compounds as antiischemic agents due to their powerful peripheral vasodilating effects, which can result in underperfusion of the area already at risk. We have recently disclosed the discovery of benzopyranylcyanoguanidine type K-ATP openers (BMS-180448) which are more selective for the ischemic myocardium compared to the first-generation compounds. This publication deals with structure-activity relationships for the antiischemic activity of the lead compound 8. The presence of an electron-withdrawing group at C6, an sp(3) center at C4, and a gem-dimethyl group at C2 appears to be essential for antiischemic activity. Cyanoguanidine can be replaced with a urea moiety. The results reported here support the hypothesis that distinct structure-activity relationships exist for antiischemic and vaso:relaxant activities of compounds related to 8 and cromakalim. The trifluoromethyl analog 10 is 550-fold more selective in vitro for the ischemic myocardium compared to the first-generation agent cromakalim. The reasons for the selectivity of these compounds for the ischemic myocardium are not clear at the present time. They may be related to the existence of receptor subtypes in smooth muscle and the myocardium.