2,2-dimethyl-N-phenyl-2H-1-benzopyran-6-carboxamide | 185316-60-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,2-dimethyl-N-phenyl-2H-1-benzopyran-6-carboxamide
• 英文别名: 2,2-dimethyl-N-phenylchromene-6-carboxamide
• CAS: 185316-60-3
• 化学式: C₁₈H₁₇NO₂
• 分子量: 279.338
• InChiKey: PPRXCJKDGJCKGC-UHFFFAOYSA-N

物化性质

• 熔点：
  152-153 °C
• 沸点：
  373.8±42.0 °C(Predicted)
• 密度：
  1.174±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,2-dimethyl-N-phenyl-2H-1-benzopyran-6-carboxamide 、 sodium N-(4-chlorophenyl)-N'-cyanocarbamimidothioate 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 18.0h， 生成 (3S,4R)-4-[[(4-chloroanilino)-(cyanoamino)methylidene]amino]-3-hydroxy-2,2-dimethyl-N-phenyl-3,4-dihydrochromene-6-carboxamide
  参考文献：
  名称：

  Cardioselective Antiischemic ATP-Sensitive Potassium Channel (K_ATP) Openers. 6. Effect of Modifications at C6 of Benzopyranyl Cyanoguanidines

  摘要：

  The effect on potency and selectivity of modifications at the C6 position of the cardioprotective K-ATP Opener BMS-180448 (2) is described. Structure-activity studies show that a variety of electron-withdrawing groups (ketone, sulfone, sulfonamide, etc.) are tolerated for cardioprotective activity as measured by EC25 values for an increase in time to the onset of contracture in globally ischemic rat, hearts. Changes made to the sulfonamido substituent indicate that compounds derived from secondary lipophilic amines are preferred for good cardioprotective potency and selectivity. The diisobutyl analogue 27 (EC25 = 0.04 mu M) is the most potent compound of this series. The cardiac selectivity of 27 results from a combination of reduced vasorelaxant potency and enhanced cardioprotective potency relative to the potent vasodilating K-ATP openers (e.g., cromakalim). The diisobutylsulfonamide analogue 27 is over 4 orders of magnitude more cardiac selective than cromakalim (1), These results support the hypothesis that the cardioprotective and vasorelaxant properties of K-ATP openers follow distinct structure-activity relationships. The mechanism of action of 27 appears to involve opening of the cardiac K-ATP as its cardioprotective effects are abolished by the K-ATP blocker glyburide.

  DOI：

  10.1021/jm990196h
• 作为产物：
  描述：

  2,2-二甲基色烯-6-羧酸 在 草酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 2,2-dimethyl-N-phenyl-2H-1-benzopyran-6-carboxamide
  参考文献：
  名称：

  Cardioselective Antiischemic ATP-Sensitive Potassium Channel (K_ATP) Openers. 6. Effect of Modifications at C6 of Benzopyranyl Cyanoguanidines

  摘要：

  The effect on potency and selectivity of modifications at the C6 position of the cardioprotective K-ATP Opener BMS-180448 (2) is described. Structure-activity studies show that a variety of electron-withdrawing groups (ketone, sulfone, sulfonamide, etc.) are tolerated for cardioprotective activity as measured by EC25 values for an increase in time to the onset of contracture in globally ischemic rat, hearts. Changes made to the sulfonamido substituent indicate that compounds derived from secondary lipophilic amines are preferred for good cardioprotective potency and selectivity. The diisobutyl analogue 27 (EC25 = 0.04 mu M) is the most potent compound of this series. The cardiac selectivity of 27 results from a combination of reduced vasorelaxant potency and enhanced cardioprotective potency relative to the potent vasodilating K-ATP openers (e.g., cromakalim). The diisobutylsulfonamide analogue 27 is over 4 orders of magnitude more cardiac selective than cromakalim (1), These results support the hypothesis that the cardioprotective and vasorelaxant properties of K-ATP openers follow distinct structure-activity relationships. The mechanism of action of 27 appears to involve opening of the cardiac K-ATP as its cardioprotective effects are abolished by the K-ATP blocker glyburide.

  DOI：

  10.1021/jm990196h

文献信息

• Selenium-Based Solid-Phase Synthesis of Benzopyrans II: Applications to Combinatorial Synthesis of Medicinally Relevant Small Organic Molecules
  作者：K. C. Nicolaou、Guo-Qiang Cao、Jeffrey A. Pfefferkorn

  DOI：10.1002/(sici)1521-3773(20000218)39:4<739::aid-anie739>3.0.co;2-z

  日期：2000.2.18
• A convenient Synthesis of 6-Substituted-2,2-Dimethyl-2<i>H</i>-1-Benzopyrans
  作者：Charles Z. Ding

  DOI：10.1080/00397919608004664

  日期：1996.11

  Various 2,2-dimethyl-6-functional-2H-1-benzopyrans were prepared via a halogen-metal exchange reaction followed by treatment with electrophiles. These 6-functionalized chromenes are important synthetic intermediates for preparation of benzopyran-based potassium channel openers.