{Reference Type}: Journal Article
{Title}: Structure optimization of Cmpd-15 as negative allosteric modulators for the β2-adrenergic receptor.
{Author}: Guo X;Luo Z;Qi Y;Hei X;Zhang X;Cao X;Qian M;Zhao S;Hou Y;Chen X;
{Journal}: Bioorg Med Chem
{Volume}: 108
{Issue}: 0
{Year}: 2024 Jun 15
{Factor}: 3.461
{DOI}: 10.1016/j.bmc.2024.117787
{Abstract}: 19 derivatives of 1-benzyl-3-arylpyrazole-5-carboxamides (H1-H19) and 5 derivatives of 1-benzyl-5-arylpyrazole-3-carboxamides (J1-J5) have been designed and synthesized as potential negative allosteric modulators (NAMs) for the β2-adrenergic receptor (β2AR). The new pyrazole derivatives were screened on the classic G-protein dependent signaling pathway at β2AR. The majority of 1-benzyl-3-aryl-pyrazole-5-carboxamide derivatives show more potent allosteric antagonistic activity against β2AR than Cmpd-15, the first reported β2AR NAM. However, the 1-benzyl-5-arylpyrazole-3-carboxamide derivatives exhibit very poor or even no allosteric antagonistic activity for β2AR. Furthermore, the active pyrazole derivatives have relative better drug-like profiles than Cmpd-15. Taken together, we discovered a series of derivatives of 1-benzyl-3-arylpyrazole-5-carboxamides as a novel scaffold of β2AR NAM.