(3'S,4'R)-N-(6-cyano-3,4-dihydro-2,2-dimethyl-3-hydroxy-2H-[1]benzopyran-4-yl)-2-acetamide | 133162-86-4

• 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: (3'S,4'R)-N-(6-cyano-3,4-dihydro-2,2-dimethyl-3-hydroxy-2H-[1]benzopyran-4-yl)-2-acetamide
• 英文别名: CGP 42022；N-[(3S,4R)-6-cyano-3-hydroxy-2,2-dimethyl-3,4-dihydrochromen-4-yl]acetamide
• CAS: 133162-86-4
• 化学式: C₁₄H₁₆N₂O₃
• 分子量: 260.293
• InChiKey: QFZMWCMMDSCJDS-OLZOCXBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  82.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3'S,4'R)-N-(6-cyano-3,4-dihydro-2,2-dimethyl-3-hydroxy-2H-[1]benzopyran-4-yl)-2-acetamide 在 二乙胺基三氟化硫 、 potassium carbonate 、 苯硫酚 、 三乙胺 、 sodium iodide 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 73.0h， 生成 (4aR,10bR)-5,5-dimethyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitrile
  参考文献：
  名称：

  N -Acyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano-[3,4- b ][1,4]oxazine-9-carbonitriles as bladder-selective potassium channel openers

  摘要：

  Optically active N-acyl-5,5-dimethyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitriles 2-22 were synthesized as rigid analogues of cromakalim. The (4aR,10br)-N-benzoyl derivative (-)-11 was identified as a bladder-selective KCO (IC50, (bladder) = 82 muM, IC50, (portal vein) = 34.5 muM). Among the analogues of 11 with substitution on the benzoyl moiety, the 3-methyl analogue (-)-14 showed highly potent and selective activity at portal vein (IC50, (bladder) = 279 muM, IC50, (portal vein) = 0.54 muM). The 4-bromo analogue (-)-19 (IC50, (bladder) = 2.0 muM, IC50, (portal vein) = 8.1 muM) and the 4-hydroxy analogue (-)-21 (IC50, (bladder) = 3.8 muM, IC50, portal vein = 75 muM) showed enhanced activity at the bladder, while maintaining unprecedented bladder selectivity in vitro. The N-benzenesulfonyl analogue (-)-22, a bioisoster of (-)-11, showed similar activity at the bladder with enhanced selectivity (IC50, bladder = 116 muM, IC50, portal vein = 120 muM) (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00260-1
• 作为产物：
  描述：

  6-cyano-2,2-dimethylchromene-3,4-epoxide 在 ammonium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 (3'S,4'R)-N-(6-cyano-3,4-dihydro-2,2-dimethyl-3-hydroxy-2H-[1]benzopyran-4-yl)-2-acetamide
  参考文献：
  名称：

  N -Acyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano-[3,4- b ][1,4]oxazine-9-carbonitriles as bladder-selective potassium channel openers

  摘要：

  Optically active N-acyl-5,5-dimethyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitriles 2-22 were synthesized as rigid analogues of cromakalim. The (4aR,10br)-N-benzoyl derivative (-)-11 was identified as a bladder-selective KCO (IC50, (bladder) = 82 muM, IC50, (portal vein) = 34.5 muM). Among the analogues of 11 with substitution on the benzoyl moiety, the 3-methyl analogue (-)-14 showed highly potent and selective activity at portal vein (IC50, (bladder) = 279 muM, IC50, (portal vein) = 0.54 muM). The 4-bromo analogue (-)-19 (IC50, (bladder) = 2.0 muM, IC50, (portal vein) = 8.1 muM) and the 4-hydroxy analogue (-)-21 (IC50, (bladder) = 3.8 muM, IC50, portal vein = 75 muM) showed enhanced activity at the bladder, while maintaining unprecedented bladder selectivity in vitro. The N-benzenesulfonyl analogue (-)-22, a bioisoster of (-)-11, showed similar activity at the bladder with enhanced selectivity (IC50, bladder = 116 muM, IC50, portal vein = 120 muM) (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00260-1

文献信息

• NOVEL BENZOPYRAN DERIVATIVE
  申请人：Japan Tobacco Inc.

  公开号：EP0536424A1

  公开（公告）日：1993-04-14

  A novel benzopyran derivative represented by general formula (I) and a pharmaceutically acceptable salt thereof, wherein each symbol is as defined in the specification. This compound is useful for treating hypertension, because it has a persistent hypotensive activity and a peripheral blood relaxing activity by activating a potassium channel, and also for treating cardiovascular diseases such as angina pectoris and heart failure, because it has a selective coronary blood stream increasing activity.

  一种由通式(I)代表的新型苯并吡喃衍生物及其药学上可接受的盐，其中各符号如说明书中所定义。这种化合物可用于治疗高血压，因为它通过激活钾通道而具有持续降压活性和外周血松弛活性；还可用于治疗心血管疾病，如心绞痛和心力衰竭，因为它具有选择性冠状动脉血流增加活性。
• Synthesis of 2,3,4a,11b-tetrahydro-oxazino[2,3-c]benzopyran-9-carbonitriles as ATP-sensitive potassium channel openers
  作者：Chen-Yu Cheng、Hsin-I Chiu、Ming-Jyh Chang、Yen-Chung Lin、Ming-Cheng Tsai、Hon-Cheng Yu

  DOI：10.1016/s0960-894x(98)00046-8

  日期：1998.3

  A series of optically active tetrahydro-oxazino[2,3-c]benzopyran derivatives have been synthesized and evaluated for potassium channel opening activity. (4aR,11bR)-1-Benzoyl-5,5-dimethyl-2,3,4a,11b-tetrahydro-oxazino[2,3-c]benzopyran-9-carbonitrile ((-)-11e) was identified as a bladder-selective potassium channel opener (IC50,bladder = 8.15 mu M, IC50,portal vein = 34.5 mu M). (C) 1998 Elsevier Science Ltd. All rights reserved.
• BURRELL, GORDON;EVANS, JOHN M.;JONES, GRAHAM E.;STEMP, GEOFFREY, TETRAHEDRON LETT., 31,(1990) N5, C. 3649-3652
  作者：BURRELL, GORDON、EVANS, JOHN M.、JONES, GRAHAM E.、STEMP, GEOFFREY

  DOI：——

  日期：——
• ASHWOOC, VALERIE A.;CASSIDY, FREDERICK;COLDWELL, MARTIN C.;EVANS, JOHN M.+, J. MED. CHEM., 33,(1990) N, C. 2667-2672
  作者：ASHWOOC, VALERIE A.、CASSIDY, FREDERICK、COLDWELL, MARTIN C.、EVANS, JOHN M.+

  DOI：——

  日期：——
• N -Acyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano-[3,4- b ][1,4]oxazine-9-carbonitriles as bladder-selective potassium channel openers
  作者：Hsin-I. Chiu、Yen-Chung Lin、Chen-Yu Cheng、Ming-Cheng Tsai、Hon-Cheng Yu

  DOI：10.1016/s0968-0896(00)00260-1

  日期：2001.2

  Optically active N-acyl-5,5-dimethyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitriles 2-22 were synthesized as rigid analogues of cromakalim. The (4aR,10br)-N-benzoyl derivative (-)-11 was identified as a bladder-selective KCO (IC50, (bladder) = 82 muM, IC50, (portal vein) = 34.5 muM). Among the analogues of 11 with substitution on the benzoyl moiety, the 3-methyl analogue (-)-14 showed highly potent and selective activity at portal vein (IC50, (bladder) = 279 muM, IC50, (portal vein) = 0.54 muM). The 4-bromo analogue (-)-19 (IC50, (bladder) = 2.0 muM, IC50, (portal vein) = 8.1 muM) and the 4-hydroxy analogue (-)-21 (IC50, (bladder) = 3.8 muM, IC50, portal vein = 75 muM) showed enhanced activity at the bladder, while maintaining unprecedented bladder selectivity in vitro. The N-benzenesulfonyl analogue (-)-22, a bioisoster of (-)-11, showed similar activity at the bladder with enhanced selectivity (IC50, bladder = 116 muM, IC50, portal vein = 120 muM) (C) 2001 Elsevier Science Ltd. All rights reserved.