Pyrrolo[2,3-b]pyridine derivatives as potent Bruton’s tyrosine kinase inhibitors

摘要: Abstract A series of pyrrolo[2,3-b]pyridine-based derivatives were designed as potent Bruton’s tyrosine kinase (BTK) inhibitors by using a scaffold-hopping strategy. Structure–activity relationship studies identified five compounds (3n, 3p, 3q, 3r, and 3s) with IC50 less than 10 nM in BTK enzyme assay (3m, 3n, 3o, 3t) 20 nM Ramos cell assay. As one the most inhibitors, compound 3p exhibited superior activity to that 1 (RN486) pyrrolo[2,3-d]pyrimidine derivative 2 both enzymatic (IC50 = 6.0 nM) cellular inhibition (IC50 = 14 nM) assays. In addition, displayed favorable overall pharmacokinetic profiles compared 2.