(3S,4R)-4-amino-6-(benzenesulfonyl)-2,2-dimethyl-3,4-dihydrochromen-3-ol | 150520-38-0

• 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: (3S,4R)-4-amino-6-(benzenesulfonyl)-2,2-dimethyl-3,4-dihydrochromen-3-ol
• CAS: 150520-38-0
• 化学式: C₁₇H₁₉NO₄S
• 分子量: 333.408
• InChiKey: FIVJVQHIVZORQH-CVEARBPZSA-N

物化性质

• 沸点：
  515.4±50.0 °C(predicted)
• 密度：
  1.289±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  98
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4R)-4-amino-6-(benzenesulfonyl)-2,2-dimethyl-3,4-dihydrochromen-3-ol 、 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 2-[(3S,4R)-6-(benzenesulfonyl)-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]-1-(4-chlorophenyl)-3-cyanoguanidine
  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-dimethyl-6-phenyl-sulfonyl-2H-chromene 在 ammonium hydroxide 、 sodium hypochlorite 、 4-苯基吡啶-N-氧化物 、 Jacobsen's catalyst 作用下， 以 四氢呋喃 、 水 、 异丙醇 为溶剂， 反应 42.0h， 生成 (3S,4R)-4-amino-6-(benzenesulfonyl)-2,2-dimethyl-3,4-dihydrochromen-3-ol
  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

• Ethanoladdukte von 6-sulfonylsubstituierten 3-Hydroxychromanen und ihre Verwendung als Inhalationsmittel bei Krankheiten
  申请人：HOECHST AKTIENGESELLSCHAFT

  公开号：EP0547523A1

  公开（公告）日：1993-06-23

  Die Erfindung betrifft Ethanoladdukte der Verbindungen der Formel I ein Verfahren zu ihrer Herstellung und ihre Verwendung als Inhalationsmittel bei Krankheiten, insbesondere bei Asthma.

  本发明涉及式 I 化合物的乙醇加合物 的制备方法，以及将其用作治疗疾病（尤其是哮喘）的吸入剂。
• 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.
• US5310753A
  申请人：——

  公开号：US5310753A

  公开（公告）日：1994-05-10
• 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.