2-Ethylamino-5-(4-methanesulfonyl-benzoyl)-4-methyl-thiophene-3-carboxylic acid methyl ester

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-Ethylamino-5-(4-methanesulfonyl-benzoyl)-4-methyl-thiophene-3-carboxylic acid methyl ester
• 英文别名: Methyl 2-(ethylamino)-4-methyl-5-[4-(methylsulfonyl)benzoyl]-3-thiophenecarboxylate；methyl 2-(ethylamino)-4-methyl-5-(4-methylsulfonylbenzoyl)thiophene-3-carboxylate
• 化学式: C₁₇H₁₉NO₅S₂
• 分子量: 381.474
• InChiKey: BAJCOJWHPHCFDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  、 2-溴-1-(4-甲磺酰基)苯乙酮 以 乙腈 为溶剂， 以99%的产率得到2-Ethylamino-5-(4-methanesulfonyl-benzoyl)-4-methyl-thiophene-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Tetra substituted thiophenes as anti-inflammatory agents: Exploitation of analogue-based drug design

  摘要：

  A series of 17 novel tetra substituted thiophenes was designed, synthesized, and screened for anti-inflammatory activity in carrageenin induced rat paw edema model, an acute in vivo model. The lead molecule selected was Tenidap, a dual COX/LOX inhibitor. Compounds 1 (43%) 111 (60%), IV (60%), and VIII (64%) showed moderate to good anti-inflammatory activity. The best candidate among the whole series was VIII, which gave 64% protection to the inflamed paw. The side chain of candidate VIII had resemblance to that of Romazarit, a DMARD, which was withdrawn due to its toxicity profile. A probable reason for the metabolic stability of the proposed side chain not having the possibility of generating peroxy type radicals or acrylic acid moieties, unlike Romazarit, is discussed. The biological activity exhibited by the three designed series was in the order of methyl amino series > ethyl amino series > carbethoxy amino series. The -(C=O)-CH2-COOR side chain at the fifth position as in candidate VIII, the methyl amino group at the second position, and the ester at the third position of the thiophene can be considered as a three-point pharmacophore for designing better anti-inflammatory agents. The present study is a classical example of the exploitation of an analogue based drug design, which culminated in the development of good anti-inflammatory agents that have the potential of becoming dual inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.044

文献信息

• Tetra substituted thiophenes as anti-inflammatory agents: Exploitation of analogue-based drug design
  作者：Ajay D. Pillai、Parendu D. Rathod、Franklin P. Xavier、Harish Padh、Vasudevan Sudarsanam、Kamala K.Vasu

  DOI：10.1016/j.bmc.2005.07.044

  日期：2005.12

  A series of 17 novel tetra substituted thiophenes was designed, synthesized, and screened for anti-inflammatory activity in carrageenin induced rat paw edema model, an acute in vivo model. The lead molecule selected was Tenidap, a dual COX/LOX inhibitor. Compounds 1 (43%) 111 (60%), IV (60%), and VIII (64%) showed moderate to good anti-inflammatory activity. The best candidate among the whole series was VIII, which gave 64% protection to the inflamed paw. The side chain of candidate VIII had resemblance to that of Romazarit, a DMARD, which was withdrawn due to its toxicity profile. A probable reason for the metabolic stability of the proposed side chain not having the possibility of generating peroxy type radicals or acrylic acid moieties, unlike Romazarit, is discussed. The biological activity exhibited by the three designed series was in the order of methyl amino series > ethyl amino series > carbethoxy amino series. The -(C=O)-CH2-COOR side chain at the fifth position as in candidate VIII, the methyl amino group at the second position, and the ester at the third position of the thiophene can be considered as a three-point pharmacophore for designing better anti-inflammatory agents. The present study is a classical example of the exploitation of an analogue based drug design, which culminated in the development of good anti-inflammatory agents that have the potential of becoming dual inhibitors. (c) 2005 Elsevier Ltd. All rights reserved.