title: Updating molecular properties during early drug discovery.
abstract: Current multiparameter optimization (MPO) strategies make use of few experimental physicochemical descriptors (i.e., solubility at physiological pH and lipophilicity in the octanol/water system). Here, we show how new trends in drug discovery (i.e., large and flexible molecules for 'difficult' targets) call for the integration of ad hoc descriptors in MPO approaches. In particular, to rank, select, and optimize drug candidates, it could be relevant to have experimental data relating to the acid-base properties and the folding of the molecule to mask polar groups (so-called 'chameleonic' properties). We propose two strategies to quantify ionization and chameleonic properties and discuss their practical integration in property criteria profiles.
authors.affiliation: University of Torino, Molecular Biotechnology and Health Sciences Department, Via Quarello, 15, 10135 Torino, Italy. Electronic address: giulia.caron@unito.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Caron
authors.affiliation: University of Torino, Molecular Biotechnology and Health Sciences Department, Via Quarello, 15, 10135 Torino, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ermondi
mesh_terms: D055598:Chemical Phenomena; D055808:Drug Discovery; D004364:Pharmaceutical Preparations / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations