Synthesis and structure–activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo [1.5-a] …

DW Engers, AY Frist, CW Lindsley, CC Hong… - Bioorganic & medicinal …, 2013 - Elsevier
DW Engers, AY Frist, CW Lindsley, CC Hong, CR Hopkins
Bioorganic & medicinal chemistry letters, 2013Elsevier
A structure–activity relationship of the 3-and 6-positions of the pyrazolo [1, 5-a] pyrimidine
scaffold of the known BMP inhibitors dorsomorphin, 1, LDN-193189, 2, and DMH1, 3, 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> …
A structure–activity relationship of the 3- and 6-positions of the pyrazolo[1,5-a]pyrimidine scaffold of the known BMP inhibitors dorsomorphin, 1, LDN-193189, 2, and DMH1, 3, 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.
Elsevier