1062368-48-2Relevant academic research and scientific papers
Structure-activity relationship study of bone morphogenetic protein (BMP) signaling inhibitors
Cuny, Gregory D.,Yu, Paul B.,Laha, Joydev K.,Xing, Xuechao,Liu, Ji-Feng,Lai, Carol S.,Deng, Donna Y.,Sachidanandan, Chetana,Bloch, Kenneth D.,Peterson, Randall T.
supporting information; scheme or table, p. 4388 - 4392 (2009/04/06)
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.
