A novel series of 4-methyl substituted pyrazole derivatives were designed, synthesized and biologically evaluated as potent glucagon receptor (GCGR) antagonists. In this study, compounds 9q, 9r, 19d and 19e showed high GCGR binding (IC₅₀ = 0.09 μM, 0.06 μM, 0.07 μM and 0.08 μM, respectively) and cyclic-adenosine monophosphate (cAMP) activities (IC₅₀ = 0.22 μM, 0.26 μM, 0.44 μM and 0.46 μM, respectively) in cell-based assays. Most importantly, the docking experiment demonstrated that compound 9r formed extensive hydrophobic interactions with the receptor binding pocket, making it justifiable to further investigate the potential of becoming a GCGR antagonist.

设计，合成和生物学评估了一系列新型的4-甲基取代的吡唑衍生物，作为有效的胰高血糖素受体（GCGR）拮抗剂。在这项研究中，化合物9q，9r，19d和19e显示出高GCGR结合力（IC _50分别 为0.09μM ，0.06μM，0.07μM和0.08μM ）和环状磷酸腺苷（cAMP）活性（IC ₅₀  = 0.22μM，在基于细胞的测定中分别为0.26μM，0.44μM和0.46μM）。最重要的是，对接实验表明，化合物9r与受体结合袋形成了广泛的疏水性相互作用，因此有理由进一步研究成为GCGR拮抗剂的潜力。