Structure-Based Design of Selective Janus Kinase 2 Imidazo[4,5-d]pyrrolo[2,3-b]pyridine Inhibitors.
Basic Information
ID: ALA3621098
Journal: ACS Med Chem Lett
Title: Structure-Based Design of Selective Janus Kinase 2 Imidazo[4,5-d]pyrrolo[2,3-b]pyridine Inhibitors.
Authors: Hart AC, Schroeder GM, Wan H, Grebinski J, Inghrim J, Kempson J, Guo J, Pitts WJ, Tokarski JS, Sack JS, Khan JA, Lippy J, Lorenzi MV, You D, McDevitt T, Vuppugalla R, Zhang Y, Lombardo LJ, Trainor GL, Purandare AV.
Abstract: Early hit to lead work on a pyrrolopyridine chemotype provided access to compounds with biochemical and cellular potency against Janus kinase 2 (JAK2). Structure-based drug design along the extended hinge region of JAK2 led to the identification of an important H-bond interaction with the side chain of Tyr 931, which improved JAK family selectivity. The 4,5-dimethyl thiazole analogue 18 demonstrated high levels of JAK family selectivity and was identified as a promising lead for the program.
CiteXplore: 26288682
DOI: 10.1021/acsmedchemlett.5b00225
Patent ID: ┄