Here, we outline the synthesis of a few 2-methoxy-6-((4-(6-morpholinopyrimidin-4-yl)piperazin-1-yl)(phenyl)methyl)phenol derivatives and assess their anti-inflammatory activity in macrophage cells that have been stimulated by LPS. Among these newly synthesized morpholinopyrimidine derivatives, 2-methoxy-6-((4-methoxyphenyl)(4-(6-morpholinopyrimidin-4-yl)piperazin-1-yl)methyl)phenol (V4) and 2-((4-fluorophenyl)(4-(6-morpholinopyrimidin-4-yl)piperazin-1-yl)methyl)-6-methoxyphenol (V8) are two of the most active compounds which can inhibit the production of NO at non-cytotoxic concentrations. Our findings also showed that compounds V4 and V8 dramatically reduced iNOS and cyclooxygenase mRNA expression (COX-2) in LPS-stimulated RAW 264.7 macrophage cells; western blot analysis showed that the test compounds decreased the amount of iNOS and COX-2 protein expression, hence inhibiting the inflammatory response. We find through molecular docking studies that the chemicals had a strong affinity for the iNOS and COX-2 active sites and formed hydrophobic interactions with them. Therefore, use of these compounds could be suggested as a novel therapeutic strategy for inflammation-associated disorders.

中文翻译：

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吗啉代嘧啶衍生物作为抗炎剂的设计、合成和生物学评价

在这里，我们概述了一些 2-甲氧基-6-((4-(6-吗啉代嘧啶-4-基)哌嗪-1-基)(苯基)甲基)苯酚衍生物的合成，并评估了它们在巨噬细胞中的抗炎活性受LPS刺激的细胞。在这些新合成的吗啉代嘧啶衍生物中，2-甲氧基-6-((4-甲氧基苯基)(4-(6-吗啉代嘧啶-4-基)哌嗪-1-基)甲基)苯酚(V4)和2-( ( 4-氟苯基)(4-(6-吗啉代嘧啶-4-基)哌嗪-1-基)甲基)-6-甲氧基苯酚( V8 )是两种最活跃的化合物，可以在非细胞毒性浓度下抑制NO的产生。我们的研究结果还表明化合物V4和V8显着降低 LPS 刺激的 RAW 264.7 巨噬细胞中 iNOS 和环氧合酶 mRNA 表达 (COX-2)；蛋白质印迹分析表明，测试化合物降低了 iNOS 和 COX-2 蛋白表达量，从而抑制炎症反应。通过分子对接研究发现，这些化学物质对iNOS和COX-2活性位点具有很强的亲和力，并与它们形成疏水相互作用。因此，这些化合物的使用可能被建议作为炎症相关疾病的新治疗策略。