A fast-track chemistry effort was initiated to evaluate the structure-activity relationshipof the 3- and 6-positions of the pyrazolo[1,5-a]pyrimidine scaffold of the known BMP inhibitors. This medicinal chemistry effort led to the identification of a potent and selective compound for ALK2 versus ALK3. The potency contributions of several 3-position substituents were evaluated with subtle structural changes leading to significant changes in potency. From these studies, a novel 5-quinoline molecule was identified and designated an MLPCN probe molecule, ML347, which shows >300-fold selectivity for ALK2 and presents the community with a selective molecular probe for further biological evaluation.

Development of a potent and ALK2 selective bone morphogenetic protein receptor (BMP) inhibitor

246th National Meeting (2013)

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