Inflammation is widely reported as a main factor for the development of chronic diseases such as cancer, diabetes, and even metabolic syndrome. Thus, the search for novel anti‐inflammatory compounds is required. Herein we describe the synthesis of a collection of peptidic pyrazinones by a convenient approach involving a multicomponent isocyanide‐based reaction followed by a tandem deprotection/oxidative cyclization step. This series of compounds were tested for their potential anti‐inflammatory capacity in an in vivo murine model, and four compounds were identified to inhibit tetradecanoylphorbol acetate (TPA)‐induced edema by more than 75 %. The two most active compounds, N‐benzyl‐2‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐2‐[2‐oxopyrazin‐1(2H)‐yl]acetamide (10 o) and N‐cyclohexyl‐2‐[2‐oxopyrazin‐1(2H)‐yl]‐2‐[4‐(trifluoromethyl)phenyl]acetamide (10 x), with methyl and trifluoromethyl groups, were also able to decrease myeloperoxidase activity and leukocyte infiltration. Moreover, 10 x decreased the thickness of TPA‐treated mouse ears, as observed in histological analysis of the tissues.

中文翻译：

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N取代的2-Oxopyrazines的两步多组分合成方法和抗炎评估

炎症被广泛报道为发展诸如癌症，糖尿病，甚至代谢综合症等慢性疾病的主要因素。因此，需要寻找新型的抗炎化合物。在本文中，我们描述了通过一种简便的方法合成一系列肽吡嗪酮的方法，该方法涉及基于多组分异氰酸酯的反应，然后进行串联脱保护/氧化环化步骤。在体内小鼠模型中测试了该系列化合物的潜在抗炎能力，已鉴定出四种化合物可抑制乙酸十四烷酰佛波醇（TPA）引起的水肿超过75％。两种活性最高的化合物N-苄基-2-（4-羟基-3,5-二甲氧基苯基）-2- [2-氧杂吡嗪-1（2 H）-基]乙酰胺（10 o）和带有甲基和三氟甲基的N-环己基-2- [2-氧杂吡嗪-1（2 H）-基] -2- [4-（三氟甲基）苯基]乙酰胺（10 x）也能够降低髓过氧化物酶活性和白细胞浸润。此外，如组织的组织学分析所观察到的，10倍减小了TPA处理的小鼠耳朵的厚度。