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Discovery of 2-aminoimidazole and 2-amino imidazolyl-thiazoles as non-xanthine human adenosine A3 receptor antagonists: SAR and molecular modeling studies†
RSC Medicinal Chemistry ( IF 4.1 ) Pub Date : 2018-03-13 00:00:00 , DOI: 10.1039/c7md00643h
Amit N. Pandya 1, 2, 3, 4 , Arshi B. Baraiya 1, 2, 3, 4 , Hitesh B. Jalani 1, 2, 3, 4 , Dhaivat Pandya 1, 2, 3, 4 , Jitendra C. Kaila 1, 2, 3, 4 , Sonja Kachler 5, 6, 7 , Veronica Salmaso 8, 9, 10, 11, 12 , Stefano Moro 8, 9, 10, 11, 12 , Karl-Norbert Klotz 5, 6, 7 , Kamala K. Vasu 1, 2, 3, 4
Affiliation  

A small-molecule combinatorial library of 24 compounds with 2-aminoimidazole and 2-aminoimidazolyl-thiazole derivatives was synthesized using a 2-chloro trityl resin. The generated compound library was tested against all the human adenosine receptors subtypes. The 2-aminoimidazole derivatives (6a–6l) showed weak to moderate affinity towards the human adenosine receptors. Further modification to 2-aminoimidazolyl-thiazole derivatives (12a–12l) resulted in an improvement of affinity at adenosine A1, A2A and A3 receptor subtypes. Compound 12b was the most potent and selective non-xanthine human adenosine A3 receptor antagonist of this series. A receptor-based modeling study was performed to explore the possible binding mode of these novel 2-aminoimidazole and 2-aminoimidazolyl-thiazole derivatives into human adenosine A1, A2A and A3 receptor subtypes.

中文翻译:

发现2-氨基咪唑和2-氨基咪唑基-噻唑类化合物作为非黄嘌呤人腺苷A 3受体拮抗剂:SAR和分子模型研究

使用2-氯三苯甲基树脂合成了24种具有2-氨基咪唑和2-氨基咪唑基-噻唑衍生物的化合物的小分子组合库。针对所有人类腺苷受体亚型对生成的化合物库进行了测试。2-氨基咪唑衍生物(6a-6l)对人腺苷受体的亲和力较弱。对2-氨基咪唑基-噻唑衍生物(12a-12l)的进一步修饰导致对腺苷A 1,A 2A和A 3受体亚型的亲和力提高。化合物12b是最有效和选择性最高的非黄嘌呤人腺苷A 3该系列的受体拮抗剂。进行了基于受体的建模研究,以探索这些新型2-氨基咪唑和2-氨基咪唑基-噻唑衍生物与人腺苷A 1,A 2A和A 3受体亚型的可能结合方式。
更新日期:2018-03-13
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