Discovery and evaluation of 1 H -pyrrolo[2,3- b ]pyridine based selective and reversible small molecule BTK inhibitors for the treatment of rheumatoid arthritis

Abstract In a pursuit to identify reversible and selective BTK inhibitors, two series based on 7 H -pyrrolo[2,3- d ]pyrimidine and 1 H -pyrrolo[2,3- b ]pyridine as the hinge binding core, have been identified. Structure activity relationship (SAR) exploration led to identification of two advanced lead molecules, 11 and 13 , which demonstrated desired BTK inhibitory potency in different cellular assays, excellent selectivity in a panel of 50 diverse kinases, favorable in vivo PK properties in mice and anti-arthritic effect in a mouse model of CIA.