(4-fluorophenyl)(6-(4-methylthiophenyl)(2H-benzo[d]1,3-dioxolan-5-yl))methan-1-ol | 625827-42-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (4-fluorophenyl)(6-(4-methylthiophenyl)(2H-benzo[d]1,3-dioxolan-5-yl))methan-1-ol
• 英文别名: (4-Fluorophenyl)-[6-(4-methylsulfanylphenyl)-1,3-benzodioxol-5-yl]methanol
• CAS: 625827-42-1
• 化学式: C₂₁H₁₇FO₃S
• 分子量: 368.429
• InChiKey: CZZYIBOSWLBFGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  64
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4-fluorophenyl)(6-(4-methylthiophenyl)(2H-benzo[d]1,3-dioxolan-5-yl))methan-1-ol 在 Oxone 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 1-(6-((4-fluorophenyl)hydroxymethyl)(2H-benzo[3,4-d]1,3-dioxolan-5-yl))-4-(methylsulfonyl)benzene
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Novel, Highly Potent Metharyl and Methcycloalkyl Cyclooxygenase-2 (COX-2) Selective Inhibitors

  摘要：

  A novel series of benzo-1,3-dioxolane metharyl derivatives was synthesized and evaluated for cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) inhibition in human whole blood (HWB). In the present study, structure-activity relationships (SAR) in the metharyl analogues were investigated. The spacer group and substitutions in the spacer group were found to be quite important for potent COX-2 inhibition. Compounds in which a methylene group (8a-c), carbonyl group (12a-c), or methylidene group (7a-c) connected cycloalkyl groups to the central benzo-1,3-dioxolane template were found to be potent and selective COX-2 inhibitors. Aryl-substituted compounds linked to the central ring by either a methylene or a carbonyl spacer resulted in potent, highly selective COX-2 inhibitors. In this series of substituted-(2H-benzo-[3,4-d] 1,3-dioxolan-5-yl)-1-(methylsulfonyl)benzene compounds, SAR studies demonstrated that substitution at the 3-position of the aryl group optimized COX-2 selectivity and potency, whereas substitution at the 4-position attenuated COX-2 inhibition. Mono- or difluoro substitution at meta position(s), as in 22c and 22h, was advantageous for both in vitro COX-2 potency and selectivity (e.g., COX-2 IC50 for 22c = 1 muM and COX-1 IC50 for 22c = 20 muM in HWB assay). Several novel compounds in the (2H-benzo[3,4-d]1,3-dioxolan-5-yl)-1-(methylsulfonyl)benzene series, as shown in structures 7c, 8a, 12a, 21c, 22c, 22e, and 22h, selectively inhibited COX-2 activity by 40-50% at a test concentration of 1 muM in an in vitro HWB assay.

  DOI：

  10.1021/jm030268b
• 作为产物：
  描述：

  6-溴-3,4-亚甲基二氧苯甲醛 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.17h， 生成 (4-fluorophenyl)(6-(4-methylthiophenyl)(2H-benzo[d]1,3-dioxolan-5-yl))methan-1-ol
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of Novel, Highly Potent Metharyl and Methcycloalkyl Cyclooxygenase-2 (COX-2) Selective Inhibitors

  摘要：

  A novel series of benzo-1,3-dioxolane metharyl derivatives was synthesized and evaluated for cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) inhibition in human whole blood (HWB). In the present study, structure-activity relationships (SAR) in the metharyl analogues were investigated. The spacer group and substitutions in the spacer group were found to be quite important for potent COX-2 inhibition. Compounds in which a methylene group (8a-c), carbonyl group (12a-c), or methylidene group (7a-c) connected cycloalkyl groups to the central benzo-1,3-dioxolane template were found to be potent and selective COX-2 inhibitors. Aryl-substituted compounds linked to the central ring by either a methylene or a carbonyl spacer resulted in potent, highly selective COX-2 inhibitors. In this series of substituted-(2H-benzo-[3,4-d] 1,3-dioxolan-5-yl)-1-(methylsulfonyl)benzene compounds, SAR studies demonstrated that substitution at the 3-position of the aryl group optimized COX-2 selectivity and potency, whereas substitution at the 4-position attenuated COX-2 inhibition. Mono- or difluoro substitution at meta position(s), as in 22c and 22h, was advantageous for both in vitro COX-2 potency and selectivity (e.g., COX-2 IC50 for 22c = 1 muM and COX-1 IC50 for 22c = 20 muM in HWB assay). Several novel compounds in the (2H-benzo[3,4-d]1,3-dioxolan-5-yl)-1-(methylsulfonyl)benzene series, as shown in structures 7c, 8a, 12a, 21c, 22c, 22e, and 22h, selectively inhibited COX-2 activity by 40-50% at a test concentration of 1 muM in an in vitro HWB assay.

  DOI：

  10.1021/jm030268b

文献信息

• Synthesis and Structure−Activity Relationship of Novel, Highly Potent Metharyl and Methcycloalkyl Cyclooxygenase-2 (COX-2) Selective Inhibitors
  作者：Subhash P. Khanapure、David S. Garvey、Delano V. Young、Maiko Ezawa、Richard A. Earl、Rick D. Gaston、Xinqin Fang、Madhavi Murty、Allison Martino、Matthew Shumway、Mark Trocha、Przemyslaw Marek、S. William Tam、David R. Janero、L. Gordon Letts

  DOI：10.1021/jm030268b

  日期：2003.12.1

  A novel series of benzo-1,3-dioxolane metharyl derivatives was synthesized and evaluated for cyclooxygenase-2 (COX-2) and cyclooxygenase-1 (COX-1) inhibition in human whole blood (HWB). In the present study, structure-activity relationships (SAR) in the metharyl analogues were investigated. The spacer group and substitutions in the spacer group were found to be quite important for potent COX-2 inhibition. Compounds in which a methylene group (8a-c), carbonyl group (12a-c), or methylidene group (7a-c) connected cycloalkyl groups to the central benzo-1,3-dioxolane template were found to be potent and selective COX-2 inhibitors. Aryl-substituted compounds linked to the central ring by either a methylene or a carbonyl spacer resulted in potent, highly selective COX-2 inhibitors. In this series of substituted-(2H-benzo-[3,4-d] 1,3-dioxolan-5-yl)-1-(methylsulfonyl)benzene compounds, SAR studies demonstrated that substitution at the 3-position of the aryl group optimized COX-2 selectivity and potency, whereas substitution at the 4-position attenuated COX-2 inhibition. Mono- or difluoro substitution at meta position(s), as in 22c and 22h, was advantageous for both in vitro COX-2 potency and selectivity (e.g., COX-2 IC50 for 22c = 1 muM and COX-1 IC50 for 22c = 20 muM in HWB assay). Several novel compounds in the (2H-benzo[3,4-d]1,3-dioxolan-5-yl)-1-(methylsulfonyl)benzene series, as shown in structures 7c, 8a, 12a, 21c, 22c, 22e, and 22h, selectively inhibited COX-2 activity by 40-50% at a test concentration of 1 muM in an in vitro HWB assay.