1-(6-Cyano-2,2-dimethylchromen-4-yl)-3-phenylurea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 1-(6-Cyano-2,2-dimethylchromen-4-yl)-3-phenylurea
• 化学式: C₁₉H₁₇N₃O₂
• 分子量: 319.363
• InChiKey: ZCBLOVRYZFRZIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  74.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (3R-trans)-4-amino-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 1-(6-Cyano-2,2-dimethylchromen-4-yl)-3-phenylurea
  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

• 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.