Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China; Department of Chemistry, Nalbari College, Assam, 781335, India.
Eur J Med Chem. 2021 Jan 15;210:113040. doi: 10.1016/j.ejmech.2020.113040. Epub 2020 Nov 24.
Antagonists of adenosine receptor are under exploration as potential drug candidates for treatment of neurological disorders, depression, certain cancers and potentially used as a cancer immunotherapy. Herein, we describe design and synthesis of novel scaffold benzo[4,5]imidazo [1,2-a]pyrazin-1-amine (6) derivatives. All the compounds were evaluated for A AR antagonist activity and displayed encouraging results (IC 9-300 nM) of A AR antagonist binding affinity in biochemical assay. Compound 27 exhibits good activity in A AR antagonist cAMP functional assay (IC 31 nM) and further this compound shows T-cell activation at the IL-2 production assay (EC 165 nM). Molecular docking studies were carried out to rationalize the observed binding affinity of compound 27.
腺嘌呤受体拮抗剂作为治疗神经紊乱、抑郁、某些癌症的潜在药物候选物正在被研究，并且可能被用作癌症免疫疗法。在此，我们描述了新型苯并[4,5]咪唑并[1,2-a]吡嗪-1-胺（6）衍生物支架的设计和合成。所有化合物均经过 A AR 拮抗剂活性评估，在生化测定中显示出令人鼓舞的 A AR 拮抗剂结合亲和力结果（IC 9-300 nM）。化合物 27 在 A AR 拮抗剂 cAMP 功能测定中表现出良好的活性（IC 31 nM），并且进一步显示在 IL-2 产生测定中 T 细胞激活（EC 165 nM）。进行了分子对接研究，以合理推断化合物 27 的观察到的结合亲和力。
