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A series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases is described. The compounds demonstrated potency with IC(50) values in the low nanomolar range in vitro while the lead compound also showed in vivo activity against various human tumor xenograft models in mice. Further exploration of this class of compounds is underway.
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http://dx.doi.org/10.1016/j.bmcl.2008.04.009 | DOI Listing |
ACS Chem Neurosci
September 2024
Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.
Herein we report progress toward a backup clinical candidate to the M positive allosteric modulator (PAM) VU319/ACP-319. Scaffold-hopping from the pyrrolo[2,3-]pyridine-based M PAM VU6007477 to isomeric pyrrolo[3,2-]pyridine and thieno[3,2-]pyridine congeners identified several backup contenders. Ultimately, VU6007496, a pyrrolo[3,2-]pyridine, advanced into late stage profiling, only to be plagued with unanticipated, species-specific metabolism and active/toxic metabolites which were identified in our phenotypic seizure liability screen, preventing further development.
View Article and Find Full Text PDFBioorg Med Chem Lett
December 2009
Department of Medicinal Chemistry, 7220 Frederick-Banting, Montréal, QC, Canada H4S 2A1.
A family of thieno[3,2-b]pyridine based small molecule inhibitors of c-Met and VEGFR2 were designed based on lead structure 2. These compounds were shown to have IC(50) values in the low nanomolar range in vitro and were efficacious in human tumor xenograft models in mice in vivo.
View Article and Find Full Text PDFBioorg Med Chem Lett
May 2008
Department of Medicinal Chemistry, MethylGene Inc., 7220 Frederick-Banting, Montréal, Que., Canada H4S 2A1.
A series of thieno[3,2-b]pyridine-based inhibitors of c-Met and VEGFR2 tyrosine kinases is described. The compounds demonstrated potency with IC(50) values in the low nanomolar range in vitro while the lead compound also showed in vivo activity against various human tumor xenograft models in mice. Further exploration of this class of compounds is underway.
View Article and Find Full Text PDF