(4aR,10bR)-5,5-dimethyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitrile | 205312-13-6

• 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: (4aR,10bR)-5,5-dimethyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitrile
• CAS: 205312-13-6
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: SPJWDGVRHDGJBR-CHWSQXEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.76
• 重原子数：
  18.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54.28
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  苯甲酰氯 、 (4aR,10bR)-5,5-dimethyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitrile 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以95%的产率得到(4aR,10bR)-1-benzoyl-5,5-dimethyl-2,3,4a,10b-tetrahydrochromeno[3,4-b][1,4]oxazine-9-carbonitrile
  参考文献：
  名称：

  Synthesis of 2,3,4a,11b-tetrahydro-oxazino[2,3-c]benzopyran-9-carbonitriles as ATP-sensitive potassium channel openers

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(98)00046-8
• 作为产物：
  描述：

  (4aR,10aR)-10,10-Dimethyl-4-(2-nitro-benzenesulfonyl)-2,3,4,4a,10,10a-hexahydro-1,9-dioxa-4-aza-phenanthrene-6-carbonitrile 在 potassium carbonate 、 苯硫酚 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以70%的产率得到(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