1-(6-(cyclohexylidenemethyl)(2H-benzo[3,4-d]1,3-dioxolan-5-yl))-4-methylthiobenzene | 445039-74-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: 1-(6-(cyclohexylidenemethyl)(2H-benzo[3,4-d]1,3-dioxolan-5-yl))-4-methylthiobenzene
• 英文别名: 5-(Cyclohexylidenemethyl)-6-(4-methylsulfanylphenyl)-1,3-benzodioxole
• CAS: 445039-74-7
• 化学式: C₂₁H₂₂O₂S
• 分子量: 338.47
• InChiKey: RWBCHFXUQOHVAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(6-(cyclohexylidenemethyl)(2H-benzo[3,4-d]1,3-dioxolan-5-yl))-4-methylthiobenzene 在 Oxone 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以56%的产率得到5-Cyclohexylidenemethyl-6-(4-methanesulfonyl-phenyl)-benzo[1,3]dioxole
  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 、 正丁基锂 、 sodium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， 反应 1.0h， 生成 1-(6-(cyclohexylidenemethyl)(2H-benzo[3,4-d]1,3-dioxolan-5-yl))-4-methylthiobenzene
  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.