title: The significance of acid/base properties in drug discovery.
abstract: While drug discovery scientists take heed of various guidelines concerning drug-like character, the influence of acid/base properties often remains under-scrutinised. Ionisation constants (pK(a) values) are fundamental to the variability of the biopharmaceutical characteristics of drugs and to underlying parameters such as logD and solubility. pK(a) values affect physicochemical properties such as aqueous solubility, which in turn influences drug formulation approaches. More importantly, absorption, distribution, metabolism, excretion and toxicity (ADMET) are profoundly affected by the charge state of compounds under varying pH conditions. Consideration of pK(a) values in conjunction with other molecular properties is of great significance and has the potential to be used to further improve the efficiency of drug discovery. Given the recent low annual output of new drugs from pharmaceutical companies, this review will provide a timely reminder of an important molecular property that influences clinical success.
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, VIC 3052, Australia. David.Manallack@monash.edu
authors.forename: David T
authors.initials: DT
authors.lastname: Manallack
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Prankerd
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Yuriev
authors.forename: Tudor I
authors.initials: TI
authors.lastname: Oprea
authors.forename: David K
authors.initials: DK
authors.lastname: Chalmers
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism*; D010599:Pharmacokinetics; D012995:Solubility
chemical_list: D004364:Pharmaceutical Preparations