1062368-72-2Relevant academic research and scientific papers
INHIBITORS OF THE BMP SIGNALING PATHWAY
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Page/Page column 70, (2009/10/22)
The present invention provides small molecule inhibitors of BMP signaling. These compounds may be used to modulate cell growth, differentiation, proliferation, and apoptosis, and thus may be useful for treating diseases or conditions associated with BMP signaling, including inflammation, cardiovascular disease, hematological disease, cancer, and bone disorders, as well as for modulating cellular differentiation and/or proliferation.
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.
