Cuny, Gregory D.Yu, Paul B.Laha, Joydev K.Xing, XuechaoLiu, Ji-FengLai, Carol S.Deng, Donna Y.Sachidanandan, ChetanaBloch, Kenneth D.Peterson, Randall T.2020-03-102020-03-102009-08Copyright 2008 Bioorganic and Medicinal Chemistry Letters. This is a post-print version of a published paper that is available at: https://www.sciencedirect.com/science/article/pii/S0960894X08007014. Recoomended citation: Cuny, Gregory D., B. Yu Paul, Joydev K. Laha, Xuechao Xing, Ji-Feng Liu, Carol S. Lai, Donna Y. Deng, Chetana Sachidanandan, Kenneth D. Bloch, and Randall T. Peterson. "Structure–activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors." Bioorganic & medicinal chemistry letters 18, no. 15 (2008): 4388-4392. doi:10.1016/j.bmcl.2008.06.052. This item has been deposited in accordance with publisher copyright and licensing terms and with the author's permission.https://hdl.handle.net/10657/5979A structure–activity relationship study of dorsomorphin, a previously identified inhibitor of SMAD 1/5/8 phosphorylation by bone morphogenetic protein (BMP) type 1 receptors ALK2, 3, and 6, revealed that increased inhibitory activity could be accomplished by replacing the pendent 4-pyridine ring with 4-quinoline. The activity contributions of various nitrogen atoms in the core pyrazolo[1,5-a]pyrimidine ring were also examined by preparing and evaluating pyrrolo[1,2-a]pyrimidine and pyrazolo[1,5-a]pyridine derivatives. In addition, increased mouse liver microsome stability was achieved by replacing the ether substituent on the pendent phenyl ring with piperazine. Finally, an optimized compound 13 (LDN-193189 or DM-3189) demonstrated moderate pharmacokinetic characteristics (e.g., plasma t1/2 = 1.6 h) following intraperitoneal administration in mice. These studies provide useful molecular probes for examining the in vivo pharmacology of BMP signaling inhibition.en-USArticle