Design and synthesis of 2-methylthio-3-substituted-5,6-dimethylthieno [2,3-d] pyrimidin-4(3H)-ones as analgesic, anti-inflammatory and antibacterial agents
Design and synthesis of 2-methylthio-3-substituted-5,6-dimethylthieno [2,3-d] pyrimidin-4(3H)-ones as analgesic, anti-inflammatory and antibacterial agents
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DOI：
10.2174/157340607779317599
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发表时间：
2007-01-01
影响因子：
2.3
通讯作者：
Murugesan, S.
中科院分区：
文献类型：
--
作者：
Alagarsamy, V.;Solomon, V. Raja;Murugesan, S.
疼痛和炎症是细菌感染的同时反应。在目前的临床实践中，两组药物如抗菌药物和非甾体抗炎药（NSAID）同时处方。令人遗憾的是，没有一种药物在单一成分中具有这些活性。利用生物电子等排原理，我们发现2-苯基-3-取代喹唑啉、2，3-二取代喹唑啉、2-甲基-3-取代喹唑啉-4-（3 H）-酮和2-甲硫基-3-取代喹唑啉-4-（3 H）-酮具有良好的镇痛和抗炎活性。本工作是我们基于生物电子等排体概念设计的2-甲硫基-3-取代-5，6-二甲基噻吩并[2，3-d]嘧啶-4（3 H）-酮先导化合物的延伸。研究了标题化合物的镇痛、抗炎和抗菌活性。虽然测试化合物显示出显著的活性，但化合物（6-9）显示出更有效的镇痛活性，并且化合物（8，9）显示出与参比标准双氯芬酸相当的抗炎活性。
Pain and inflammation are simultaneous responses in bacterial infections. In current clinical practice, two groups of agents like antibacterial and non-steroidal anti-inflammatory drugs (NSAID's) are prescribed simultaneously. Regrettably, none of the drug possesses these activities in a single component. Exploiting the bioisosterism concept, we have documented that 2-phenyl-3 -substituted quinazolines, 2,3-disubstituted quinazolines, 2-methyl-3 -substituted quinazolin-4-(3H)-ones and 2-methylthio-3 -substituted quinazolin-4-(3H)-ones exhibited good analgesic and anti-inflammatory activities. The present work is an extension of our ongoing efforts towards the development and identification of lead molecules by bioisostere concept, for which we designed some of 2-methylthio-3-substituted-5,6-dimethylthieno[2,3-d] pyrimidin-4(3H)-ones. The title compounds were investigated for analgesic, anti-inflammatory and antibacterial activities. While the test compounds exhibited significant activity, the compounds (6-9) showed more potent analgesic activity, and the compounds (8, 9) showed anti-inflammatory activity comparable to the reference standard diclofenac.