4-((2',3'-dihydrobenzofuran-7'-carbonyl)amino)-1-methyl-3-n-propylpyrazole-5-carboxamide | 258270-58-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 4-((2',3'-dihydrobenzofuran-7'-carbonyl)amino)-1-methyl-3-n-propylpyrazole-5-carboxamide
• 英文别名: 4-(2,3-Dihydro-7-benzofuroyl)amino-1-methyl-3-propyl-5-pyrazolecarboxamide；4-(2,3-Dihydro-1-benzofuran-7-carbonylamino)-2-methyl-5-propylpyrazole-3-carboxamide
• CAS: 258270-58-5
• 化学式: C₁₇H₂₀N₄O₃
• 分子量: 328.371
• InChiKey: HYUJAGDUNSGVKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  99.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-((2',3'-dihydrobenzofuran-7'-carbonyl)amino)-1-methyl-3-n-propylpyrazole-5-carboxamide 在 氯磺酸 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 生成 5-(5'-chlorosulfonyl-2',3'-dihydrobenzofuran-7'-yl)-1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
  参考文献：
  名称：

  Synthesis and phosphodiesterase 5 inhibitory activity of novel phenyl ring modified sildenafil analogues

  摘要：

  New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a-d and 7a-d, were efficiently synthesized from the readily available starting materials, 1a-d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2-3 degrees for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12-16 degrees for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23 degrees compared with the target compounds, 6a-d and 7a-d. In the enzyme assay, however, the in Vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of coplanarity. In other words, the least planar sildenafil showed the highest activity, and the most planar 5-membered cyclic ether derivatives were least active by 100-200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00055-4
• 作为产物：
  描述：

  2,3-二氢苯并呋喃-7-羧酸 在 4-二甲氨基吡啶 、 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 4-((2',3'-dihydrobenzofuran-7'-carbonyl)amino)-1-methyl-3-n-propylpyrazole-5-carboxamide
  参考文献：
  名称：

  Synthesis and phosphodiesterase 5 inhibitory activity of novel phenyl ring modified sildenafil analogues

  摘要：

  New sildenafil analogues containing an ether ring fused into the phenyl moiety, 6a-d and 7a-d, were efficiently synthesized from the readily available starting materials, 1a-d and 2, in five steps. Ab initio calculations indicated that introduction of a cyclic ether to the phenyl group might enhance the co-planarity of the molecule. The torsional angles were calculated to be 2-3 degrees for the 5-membered cyclic ether derivatives, 6a, 6c, 7a, and 7c, and 12-16 degrees for the 6-membered ones, 6b, 6d, 7b, and 7d. On the other hand, sildenafil showed the least co-planarity with the torsional angle of 23 degrees compared with the target compounds, 6a-d and 7a-d. In the enzyme assay, however, the in Vitro PDE 5 inhibitory activity was found out to be inversely related to the degree of coplanarity. In other words, the least planar sildenafil showed the highest activity, and the most planar 5-membered cyclic ether derivatives were least active by 100-200-fold compared with sildenafil. Our study clearly demonstrated that the open chain 2'-alkoxy group of the phenyl ring, although less effective for inducing the co-planarity, seemed to act as a much better lipophilic requirement than the cyclic alkoxy moiety. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00055-4

文献信息

• Voelter, Wolfgang; El-Abadelah, Mustafa M.; Sabri, Salim S., Zeitschrift fur Naturforschung, B: Chemical Sciences, 1999, vol. 54, # 11, p. 1469 - 1473
  作者：Voelter, Wolfgang、El-Abadelah, Mustafa M.、Sabri, Salim S.、Khanfar, Monther A.

  DOI：——

  日期：——