- ALKOXY TETRAHYDRO-PYRIDOPYRIMIDINE PDE10 INHIBITORS
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The present invention is directed to alkoxy tetrahydro-pyridopyrimidine compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates
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Page/Page column 48
(2010/12/26)
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- Structure-activity relationship study of EphB3 receptor tyrosine kinase inhibitors
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A structure-activity relationship study for a 2-chloroanilide derivative of pyrazolo[1,5-a]pyridine revealed that increased EphB3 kinase inhibitory activity could be accomplished by retaining the 2-chloroanilide and introducing a phenyl or small electron donating substituents to the 5-position of the pyrazolo[1,5-a]pyridine. In addition, replacement of the pyrazolo[1,5-a]pyridine with imidazo[1,2-a]pyridine was well tolerated and resulted in enhanced mouse liver microsome stability. The structure-activity relationship for EphB3 inhibition of both heterocyclic series was similar. Kinase inhibitory activity was also demonstrated for representative analogs in cell culture. An analog (32, LDN-211904) was also profiled for inhibitory activity against a panel of 288 kinases and found to be quite selective for tyrosine kinases. Overall, these studies provide useful molecular probes for examining the in vitro, cellular and potentially in vivo kinase-dependent function of EphB3 receptor.
- Qiao, Lixin,Choi, Sungwoon,Case, April,Gainer, Thomas G.,Seyb, Kathleen,Glicksman, Marcie A.,Lo, Donald C.,Stein, Ross L.,Cuny, Gregory D.
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supporting information; experimental part
p. 6122 - 6126
(2010/06/16)
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- Interactive SAR studies: Rational discovery of super-potent and highly selective dopamine D3 receptor antagonists and partial agonists
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Starting from dopamine receptor ligand BP897, an interactive drug discovery process leading to heterocyclic bioisosteres is demonstrated. The four step strategy involved a careful optimization of geometric and electronic properties by systematic modificat
- Bettinetti, Laura,Schlotter, Karin,Hübner, Harald,Gmeiner, Peter
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p. 4594 - 4597
(2007/10/03)
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- Synthesis of 2,6-disubstituted pyridines by lithiation of pyrazolo[1,5-a] pyridines
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Lithiation of 3-(4,4-dimethyl-2-oxazolin-2-yl)pyrazolo[1,5-a]pyridine (1a); with 2 molar equivalents of n-BuLi followed by reaction with benzaldehyde) yielded α-(4,4-dimethyl-2-oxazolidinylidene)-6-(α-hydroxybenzyl)- 2-pyridineacetonitrile (2a). Upon simi
- Miyashita,Sato,Watanabe,Tanji,Higashino
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p. 174 - 176
(2007/10/02)
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