(4aS,10aR)-10,10-Dimethyl-4-(3-nitro-benzoyl)-2,3,4,4a,10,10a-hexahydro-1,9-dioxa-4-aza-phenanthrene-6-carbonitrile | 340321-11-1

• 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: (4aS,10aR)-10,10-Dimethyl-4-(3-nitro-benzoyl)-2,3,4,4a,10,10a-hexahydro-1,9-dioxa-4-aza-phenanthrene-6-carbonitrile
• CAS: 340321-11-1
• 化学式: C₂₁H₁₉N₃O₅
• 分子量: 393.399
• InChiKey: RNYZCPOVYRXDPD-RBUKOAKNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.22
• 重原子数：
  29.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  105.7
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (4aS,10aR)-10,10-Dimethyl-4-(3-nitro-benzoyl)-2,3,4,4a,10,10a-hexahydro-1,9-dioxa-4-aza-phenanthrene-6-carbonitrile 以 N,N-二甲基甲酰胺 为溶剂， 以85%的产率得到(4aR,10aR)-10,10-Dimethyl-4-(3-nitro-benzoyl)-2,3,4,4a,10,10a-hexahydro-1,9-dioxa-4-aza-phenanthrene-6-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：

  (3R,4S)-3-Hydroxy-4-(2-hydroxy-ethylamino)-2,2-dimethyl-chroman-6-carbonitrile 在 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 生成 (4aS,10aR)-10,10-Dimethyl-4-(3-nitro-benzoyl)-2,3,4,4a,10,10a-hexahydro-1,9-dioxa-4-aza-phenanthrene-6-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