1-(4-chlorophenyl)-3-hydroxy-1-<(1H-1,2,4-triazol-1-yl)methyl>-1,3-dihydroisobenzofuran | 115615-31-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: 1-(4-chlorophenyl)-3-hydroxy-1-<(1H-1,2,4-triazol-1-yl)methyl>-1,3-dihydroisobenzofuran
• 英文别名: 3-(4-CHLOROPHENYL)-3-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIHYDROISOBENZOFURAN-1OL；3-(4-chlorophenyl)-3-(1,2,4-triazol-1-ylmethyl)-1H-isobenzofuran-1-ol；3-(4-chlorophenyl)-3-(1,2,4-triazol-1-ylmethyl)-1H-2-benzofuran-1-ol
• CAS: 115615-31-1
• 化学式: C₁₇H₁₄ClN₃O₂
• 分子量: 327.77
• InChiKey: SRWHPWFUWXNUSV-UHFFFAOYSA-N

物化性质

• 熔点：
  215-217 °C
• 沸点：
  544.8±60.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  60.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-chlorophenyl)-3-hydroxy-1-<(1H-1,2,4-triazol-1-yl)methyl>-1,3-dihydroisobenzofuran 、 硼氢化钠 生成 1-(4-chlorophenyl)-1-<2-(hydroxymethyl)phenyl>-2-(1H-1,2,4-triazol-1-yl)ethanol
  参考文献：
  名称：

  LOVEY, RAYMOND G.;ELLIOTT, ARTHUR J.

  摘要：

  DOI：
• 作为产物：
  描述：

  2-溴苯甲醛乙烯醛 在 草酸 、 magnesium 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 1-(4-chlorophenyl)-3-hydroxy-1-<(1H-1,2,4-triazol-1-yl)methyl>-1,3-dihydroisobenzofuran
  参考文献：
  名称：

  Isobenzofurans as conformationally constrained miconazole analogs with improved antifungal potency

  摘要：

  A series of halogen-substituted isobenzofuran analogues was synthesized, which represented conformationally constrained analogues of miconazole (1). In vitro and vivo topical antifungal activity against both dermatophytes and candida species varied widely, but 13c proved to be significantly superior to both 1 and clotrimazole against a vaginal Candida infection in hamsters, while 13b was significantly more active than 1 against a a topical Trichophyton infection in guinea pigs. None of the compounds were orally active. When the most direct analogue of 1 proved to be among the least active, a molecular modeling study was done using 1, the two active analogues 13b and 13c, and the inactive analogue 13a. All four compounds possessed skeletally similar conformations either at or energetically readily accessible from the global minimum energy conformations. This common conformation of the inactive analogue 13a, however, occupies unique molecular volume space associated with two chlorine atoms, which must also present unique electrostatic properties at the receptor. The conformation-activity relationships discussed may contribute toward deduction of additional structural requirements for pharmacophore optimization and more efficacious antifungal drugs.

  DOI：

  10.1021/jm00100a030

文献信息

• LOVEY, RAYMOND G.;ELLIOTT, ARTHUR J.
  作者：LOVEY, RAYMOND G.、ELLIOTT, ARTHUR J.

  DOI：——

  日期：——
• US4737508A
  申请人：——

  公开号：US4737508A

  公开（公告）日：1988-04-12
• US4877801A
  申请人：——

  公开号：US4877801A

  公开（公告）日：1989-10-31
• Isobenzofurans as conformationally constrained miconazole analogs with improved antifungal potency
  作者：Raymond G. Lovey、Arthur J. Elliott、James J. Kaminski、David Loebenberg、Raulo M. Parmegiani、D. F. Rane、Viyyoor M. Girijavallabhan、Russel E. Pike、Henry Guzik

  DOI：10.1021/jm00100a030

  日期：1992.10

  A series of halogen-substituted isobenzofuran analogues was synthesized, which represented conformationally constrained analogues of miconazole (1). In vitro and vivo topical antifungal activity against both dermatophytes and candida species varied widely, but 13c proved to be significantly superior to both 1 and clotrimazole against a vaginal Candida infection in hamsters, while 13b was significantly more active than 1 against a a topical Trichophyton infection in guinea pigs. None of the compounds were orally active. When the most direct analogue of 1 proved to be among the least active, a molecular modeling study was done using 1, the two active analogues 13b and 13c, and the inactive analogue 13a. All four compounds possessed skeletally similar conformations either at or energetically readily accessible from the global minimum energy conformations. This common conformation of the inactive analogue 13a, however, occupies unique molecular volume space associated with two chlorine atoms, which must also present unique electrostatic properties at the receptor. The conformation-activity relationships discussed may contribute toward deduction of additional structural requirements for pharmacophore optimization and more efficacious antifungal drugs.