N,N-diethyl-2,2-dimethyl-2H-1-benzopyran-6-sulfonamide | 186181-08-8

• 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: N,N-diethyl-2,2-dimethyl-2H-1-benzopyran-6-sulfonamide
• 英文别名: N,N-diethyl-2,2-dimethylchromene-6-sulfonamide
• CAS: 186181-08-8
• 化学式: C₁₅H₂₁NO₃S
• 分子量: 295.403
• InChiKey: RXAHWCNFUWDOBT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-diethyl-2,2-dimethyl-2H-1-benzopyran-6-sulfonamide 在 ammonium hydroxide 、 sodium hypochlorite 、 4-苯基吡啶-N-氧化物 、 Jacobsen's catalyst 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 60.0h， 生成 (3S-trans)-N-(4-chlorophenyl)-N'-cyano-N''-[6-[(diethylamino)sulfonyl]-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-4-yl]guanidine
  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：

  二乙胺 、 2,2-dimethyl-2H-1-benzopyran-6-sulfonyl chloride 以 二氯甲烷 为溶剂， 反应 2.0h， 以100%的产率得到N,N-diethyl-2,2-dimethyl-2H-1-benzopyran-6-sulfonamide
  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

• Sulfonamido substituted benzopyran derivatives
  申请人：Bristol-Myers Squibb Company

  公开号：US05869478A1

  公开（公告）日：1999-02-09

  ##STR1## and pharmaceutically acceptable salts thereof wherein Y is a single bond, --CH.sub.2 --, --C(O)--, --O--, --S-- or --N(R.sup.14)--; and R.sup.1 to R.sup.7 are as defined herein. These compounds have potassium channel activating activity and are useful, therefore for example, as cardiovascular agents.

  本发明涉及化合物及其药物学上可接受的盐，其中化合物的结构式如下：##STR1## 其中Y是单键，--CH.sub.2 --，--C（O）--，--O--，--S--或--N（R.sup.14）--；R.sup.1至R.sup.7如本文所定义。这些化合物具有钾通道激活活性，因此例如可用作心血管药物。
• Sulfonamido substituted benzopyran potassium channel activators
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP0747374A1

  公开（公告）日：1996-12-11

  The invention refers to compounds of the following formula and pharmaceutically acceptable salts thereof wherein Y is a single bond, -CH2- , -C(O)-, -O- , -S- or -N(R14)-. These compounds have potassium channel activating activity and are useful, therefore for example, as cardiovascular agents.

  本发明涉及下式化合物 及其药学上可接受的盐类，其中 Y 为单键、-CH2-、-C(O)-、-O-、-S- 或 -N(R14)-。 这些化合物具有激活钾通道的活性，因此可用作心血管药物等。
• Discovery and structure–activity relationships of a novel series of benzopyran-based KATP openers for urge urinary incontinence
  作者：Xuqing Zhang、Yuhong Qiu、Xiaojie Li、Sheela Bhattacharjee、Morgan Woods、Patricia Kraft、Scott G. Lundeen、Zhihua Sui

  DOI：10.1016/j.bmc.2008.11.055

  日期：2009.1

  A novel series of benzopyran derivatives were synthesized and evaluated as K(ATP) channel openers. Structure-activity relationships were investigated around 4-position of the benzopyran nucleus. Optimization of 4-substituent with some heterocyclic rings led to compound 13b bearing a benzo[d] isoxazol-3-one moiety as a potent and selective KATP channel opener in vitro. In two anesthetized rat models of myogenic bladder overactivity, compound 13b was found to inhibit spontaneous bladder contractions. (C) 2008 Elsevier Ltd. All rights reserved.
• US5869478A
  申请人：——

  公开号：US5869478A

  公开（公告）日：1999-02-09
• Cardioselective Antiischemic ATP-Sensitive Potassium Channel (K_A_TP) Openers. 6. Effect of Modifications at C6 of Benzopyranyl Cyanoguanidines
  作者：Charles Z. Ding、George C. Rovnyak、Raj N. Misra、Gary J. Grover、Arthur V. Miller、Syed Z. Ahmed、Yolanda Kelly、Diane E. Normandin、Paul G. Sleph、Karnail S. Atwal

  DOI：10.1021/jm990196h

  日期：1999.9.1

  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.