A new structure-based QSAR method affords both descriptive and predictive models for phosphodiesterase-4 inhibitors.

ABSTRACT: We describe the application of a new QSAR (quantitative structure-activity relationship) formalism to the analysis and modeling of PDE-4 inhibitors. This new method takes advantage of the X-ray structural information of the PDE-4 enzyme to characterize the small molecule inhibitors. It calculates molecular descriptors based on the matching of their pharmacophore feature pairs with those (the reference) of the target binding pocket. Since the reference is derived from the X-ray crystal structures of the target under study, these descriptors are target-specific and easy to interpret. We have analyzed 35 indole derivative-based PDE-4 inhibitors where Partial Least Square (PLS) analysis has been employed to obtain the predictive models. Compared to traditional QSAR methods such as CoMFA and Co

SUBMITTER: Dong X 

PROVIDER: S-EPMC2803435 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature