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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538451 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.5b00225 | DOI Listing |
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