title: Atom type preferences, structural diversity, and property profiles of known drugs, leads, and nondrugs: a comparative assessment.
abstract: A new characterization of known drug, lead, and representative nondrug databases was performed taking into account several properties at the atomic and molecular levels. This characterization included atom type preferences, intrinsic structural diversity (Atom Type Diversity, ATD), and other well-known physicochemical properties, as an approach for rapid assessment of druglikeness for small molecule libraries. To characterize ATD, an elaborate united atom classification, UALOGP (United Atom Log P), with 148 atom types, was developed along with associated atomic physicochemical parameters. This classification also enabled an analysis of atom type and physicochemical property distributions (for calculated log P, molar refractivity, molecular weight, total atom count, and ATD) of drug, lead, and nondrug databases, a reassessment of the Ro5 (Rule of Five) and GVW (Ghose−Viswanadhan−Wendoloski) criteria, and development of new criteria and ranges more accurately reflecting the chemical space occupied by small molecule drugs. A relative druglikeness parameter was defined for atom types in drugs, identifying the most preferred types. The present work demonstrates that drug molecules are constitutionally more diverse relative to nondrugs, while being less diverse than leads.
authors.affiliation: Department of Computational Chemistry, Jubilant Biosys Limited , #96, Industrial Suburb, second Stage, Yeshwanthpur, Bangalore 560 064, India. vellarkad_viswanadhan@jubilantbiosys.com
authors.forename: Vellarkad N
authors.initials: VN
authors.lastname: Viswanadhan
authors.forename: Hariharan
authors.initials: H
authors.lastname: Rajesh
authors.forename: Vitukudi N
authors.initials: VN
authors.lastname: Balaji
mesh_terms: D003628:Database Management Systems; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry*
chemical_list: D004364:Pharmaceutical Preparations