Structure–activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors
| dc.contributor.author | Cuny, Gregory D. | |
| dc.contributor.author | Yu, Paul B. | |
| dc.contributor.author | Laha, Joydev K. | |
| dc.contributor.author | Xing, Xuechao | |
| dc.contributor.author | Liu, Ji-Feng | |
| dc.contributor.author | Lai, Carol S. | |
| dc.contributor.author | Deng, Donna Y. | |
| dc.contributor.author | Sachidanandan, Chetana | |
| dc.contributor.author | Bloch, Kenneth D. | |
| dc.contributor.author | Peterson, Randall T. | |
| dc.date.accessioned | 2020-03-10T17:32:22Z | |
| dc.date.available | 2020-03-10T17:32:22Z | |
| dc.date.issued | 2009-08 | |
| dc.description.abstract | A 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. | |
| dc.identifier.citation | Copyright 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. | |
| dc.identifier.uri | https://hdl.handle.net/10657/5979 | |
| dc.language.iso | en_US | |
| dc.publisher | Bioorganic and Medicinal Chemistry Letters | |
| dc.title | Structure–activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors | |
| dc.type | Article |