Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, 1-403, Yoshino-Cho, Kita-Ku, Saitama, Saitama 331-9530, Japan.
Bioorg Med Chem Lett. 2012 Mar 1;22(5):2024-9. doi: 10.1016/j.bmcl.2012.01.066. Epub 2012 Jan 28.
A novel series of 4-thiazolylimidazoles was synthesized as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-β-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. N-{[5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-2-yl]methyl}butanamide 20, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC(50)=8.2nM) as well as inhibitory activity against TGF-β-induced Smad2/3 phosphorylation at a cellular level (IC(50)=32nM).
合成了一系列新型的 4-噻唑基咪唑类化合物作为转化生长因子-β（TGF-β）I 型受体（也称为激活素受体样激酶 5 或 ALK5）抑制剂。在酶测定法中评估了这些化合物对 ALK5 的抑制活性，以及在基于细胞的测定法中对 TGF-β 诱导的 Smad2/3 磷酸化的抑制活性。N-[[5-(1,3-苯并噻唑-6-基)-4-(4-甲基-1,3-噻唑-2-基)-1H-咪唑-2-基]甲基]丁酰胺 20 是一种有效的、选择性的 ALK5 抑制剂，对 TGF-β 诱导的 Smad2/3 磷酸化在细胞水平上具有良好的抑制活性（IC50=32nM）。
