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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors.

A papaverine based pharmacophore model for PDE10A inhibition was generated via SBDD and used to design a library of 4-amino-6,7-dimethoxyquinazolines. From this library emerged an aryl ether pyrrolidyl 6,7-dimethoxyquinazoline series that became the focal point for additional modeling, X-ray, and synthetic efforts toward increasing PDE10A inhibitory potency and selectivity versus PDE3A/B. These efforts culminated in the discovery of 29, a potent and selective brain penetrable inhibitor of PDE10A.[1]

References

  1. Discovery of a series of 6,7-dimethoxy-4-pyrrolidylquinazoline PDE10A inhibitors. Chappie, T.A., Humphrey, J.M., Allen, M.P., Estep, K.G., Fox, C.B., Lebel, L.A., Liras, S., Marr, E.S., Menniti, F.S., Pandit, J., Schmidt, C.J., Tu, M., Williams, R.D., Yang, F.V. J. Med. Chem. (2007) [Pubmed]
 
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