(6-benzoyl-3,4-dimethylcyclohex-3-enyl)(phenyl)methanone | 975-70-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (6-benzoyl-3,4-dimethylcyclohex-3-enyl)(phenyl)methanone
• 英文别名: cis-1,2-Dimethyl-4,5-dibenzoyl-cyclohexen-(1)；1.2-dimethyl-4r.5c-dibenzoyl-cyclohexene-(1)；1.2-Dimethyl-4r.5c-dibenzoyl-cyclohexen-(1)；[(1R,6S)-6-benzoyl-3,4-dimethylcyclohex-3-en-1-yl]-phenylmethanone
• CAS: 975-70-2
• 化学式: C₂₂H₂₂O₂
• 分子量: 318.415
• InChiKey: AQRCGRWLZDMDSZ-BGYRXZFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (6-benzoyl-3,4-dimethylcyclohex-3-enyl)(phenyl)methanone 在 10percent Pd/C 乙酸铵 、 ammonium formate 作用下， 以 乙醇 为溶剂， 生成 1,3-diphenyl-5,6-dimethyl-4,5,6,7-tetrahydro-2H-isoindole
  参考文献：
  名称：

  1,3-Diaryl-4,5,6,7-tetrahydro-2H-isoindole Derivatives:  A New Series of Potent and Selective COX-2 Inhibitors in Which a Sulfonyl Group Is Not a Structural Requisite

  摘要：

  Novel tetrahydro-2H-isoindoles have been prepared and evaluated as inhibitors of the COX-2 isoenzyme. A 1,S-diaryl substitution on the central polycyclic ring system and absence of a sulfonyl moiety are the two structural features of this chemical series. A short and easy synthetic pathway produced several derivatives which were shown to be potent and selective COX-2 vs COX-1 inhibitors (IC50 = 0.6-100 nM for COX-2, 100->1000 nM for COX-1). Structural modifications established that a bicyclic ring appended to the pyrrole nucleus and 4,4'-difluoro substitution on the phenyl rings were optimal for high inhibitory potency. Activity was confirmed in the human whole blood assay and subsequently in the murine air-pouch model in which in vivo PGE2 inhibitory activity was evaluated with respect to gastric tolerance (ED50 for inhibition of exudate PGE2 of 3 mg/kg and gastric PGEB of 20 mg/kg). Gastric tolerance was further assessed after administration to mice of high doses (up to 400 mg/kg) of the inhibitors by measurement of gastric damage. This panel of studies allowed selection of a number of tetrahydro-2H-isoindoles which were compared in the adjuvant-induced arthritis model. Compounds 32 and 37 showed the most potent activity with ED50 values for edema inhibition in the noninjected paw of 0.35 and 0.15 mg/kg/day, respectively, after oral administration. In addition, this interesting antiinflammatory profile was accompanied by a protective effect against arthritis-induced osteopenia, the decrease being 50% with a dose of 0.25 mg/kg/day.

  DOI：

  10.1021/jm990965x
• 作为产物：
  描述：

  (Z)-1,4-二苯基-2-丁烯-1,4-二酮 、 2,3-二甲基-1,3-丁二烯 在 1,4-二氧六环 作用下， 生成 (6-benzoyl-3,4-dimethylcyclohex-3-enyl)(phenyl)methanone
  参考文献：
  名称：

  Sauer et al., Chemische Berichte, 1964, vol. 97, p. 3208

  摘要：

  DOI：

文献信息

• The Synthesis of 1,3-Diphenyldihydroisobenzofurans, 1,3-Diphenylisobenzofurans and o-Dibenzoylbenzenes from the Diene Addition Products to Dibenzoylethylene
  作者：Roger Adams、Marvin H. Gold

  DOI：10.1021/ja01858a012

  日期：1940.1
• Sauer et al., Chemische Berichte, 1964, vol. 97, p. 3208
  作者：Sauer et al.

  DOI：——

  日期：——
• 1,3-Diaryl-4,5,6,7-tetrahydro-2<i>H</i>-isoindole Derivatives:  A New Series of Potent and Selective COX-2 Inhibitors in Which a Sulfonyl Group Is Not a Structural Requisite
  作者：Bernard Portevin、Charles Tordjman、Philippe Pastoureau、Jacqueline Bonnet、Guillaume De Nanteuil

  DOI：10.1021/jm990965x

  日期：2000.11.1

  Novel tetrahydro-2H-isoindoles have been prepared and evaluated as inhibitors of the COX-2 isoenzyme. A 1,S-diaryl substitution on the central polycyclic ring system and absence of a sulfonyl moiety are the two structural features of this chemical series. A short and easy synthetic pathway produced several derivatives which were shown to be potent and selective COX-2 vs COX-1 inhibitors (IC50 = 0.6-100 nM for COX-2, 100->1000 nM for COX-1). Structural modifications established that a bicyclic ring appended to the pyrrole nucleus and 4,4'-difluoro substitution on the phenyl rings were optimal for high inhibitory potency. Activity was confirmed in the human whole blood assay and subsequently in the murine air-pouch model in which in vivo PGE2 inhibitory activity was evaluated with respect to gastric tolerance (ED50 for inhibition of exudate PGE2 of 3 mg/kg and gastric PGEB of 20 mg/kg). Gastric tolerance was further assessed after administration to mice of high doses (up to 400 mg/kg) of the inhibitors by measurement of gastric damage. This panel of studies allowed selection of a number of tetrahydro-2H-isoindoles which were compared in the adjuvant-induced arthritis model. Compounds 32 and 37 showed the most potent activity with ED50 values for edema inhibition in the noninjected paw of 0.35 and 0.15 mg/kg/day, respectively, after oral administration. In addition, this interesting antiinflammatory profile was accompanied by a protective effect against arthritis-induced osteopenia, the decrease being 50% with a dose of 0.25 mg/kg/day.