Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties.

ABSTRACT: The interplay among commonly used physicochemical properties in drug design was examined and utilized to create a prospective design tool focused on the alignment of key druglike attributes. Using a set of six physicochemical parameters ((a) lipophilicity, calculated partition coefficient (ClogP); (b) calculated distribution coefficient at pH = 7.4 (ClogD); (c) molecular weight (MW); (d) topological polar surface area (TPSA); (e) number of hydrogen bond donors (HBD); (f) most basic center (pK(a))), a druglikeness central nervous system multiparameter optimization (CNS MPO) algorithm was built and applied to a set of marketed CNS drugs (N = 119) and Pfizer CNS candidates (N = 108), as well as to a large diversity set of Pfizer proprietary compounds (N = 11 303). The novel CNS MPO algorithm

SUBMITTER: Wager TT 

PROVIDER: S-EPMC3368654 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature