1-[(3R,4S)-6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-3-phenylurea | 128360-37-2

• 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-[(3R,4S)-6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-3-phenylurea
• CAS: 128360-37-2
• 化学式: C₁₉H₁₉N₃O₃
• 分子量: 337.378
• InChiKey: WQKPRDCCTXPCNO-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  94.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[(3R,4S)-6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-3-phenylurea 在 吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 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
• 作为产物：
  描述：

  3,4-epoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile 在 氨 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 96.25h， 生成 1-[(3R,4S)-6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-3-phenylurea
  参考文献：
  名称：

  4-（取代-羰基氨基）-2H-1-苯并吡喃的合成及降压活性。

  摘要：

  描述了口服给予有意识的自发性高血压大鼠的一系列新型4-（取代-羰基氨基）-2H-1-苯并吡喃-3-醇的合成和降压活性。对于具有在羰基侧翼的烷基，氨基或芳基的化合物，观察到最佳活性。在烷基和氨基系列中，最有效的化合物分别包含甲基和甲基氨基。已使用-86作为标记物，将几种类似物与cromakalim（1）对兔肠系膜动脉钾离子外流的作用进行了比较。每种化合物增强rub 86流出的能力与其降血压活性大致平行​​，因此这些类似物（如化合物（1））属于已归类为钾通道激活剂的一系列药物。

  DOI：

  10.1021/jm00171a051

文献信息

• Benzopyran derivatives and heterocyclic analogs thereof as antiischemic agents
  申请人：E.R. SQUIBB & SONS, INC.

  公开号：EP0462761A2

  公开（公告）日：1991-12-27

  A new method for the treatment of ischemic conditions and arrhythmia is disclosed. The method uses compounds of the formula wherein A can be -CH₂-, -O-, -NR₉-, -S-, -SO-, -SO₂-; X can be oxygen or sulfur; Y can be -NR₈, -O-, -S-, -CH₂- and the R groups are as defined herein. Novel compounds within the definition of formula I are also disclosed.

  本研究公开了一种治疗缺血性疾病和心律失常的新方法。该方法使用式 其中 A 可以是-CH₂-、-O-、-NR₉-、-S-、-SO-、-SO₂-；X 可以是氧或硫；Y 可以是-NR₈、-O-、-S-、-CH₂-，R 基团如本文所定义。还公开了符合式 I 定义的新型化合物。
• JPH04243852A
  申请人：——

  公开号：JPH04243852A

  公开（公告）日：1992-08-31
• US5276168A
  申请人：——

  公开号：US5276168A

  公开（公告）日：1994-01-04
• US5466817A
  申请人：——

  公开号：US5466817A

  公开（公告）日：1995-11-14