Work

The significance of acid/base properties in drug discovery

Year: 2012

Type: review

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.

Source: Chemical Society Reviews

DOI: 10.1039/c2cs35348b

Authors: David T. Manallack, Richard J. Prankerd, Elizabeth Yuriev, Tudor I. Oprea, David K. Chalmers

Institutions: Monash University, University of New Mexico, University of New Mexico Health Sciences Center

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Drug Discovery

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of Mental Health, National Institute of General Medical Sciences

Awards: G6285564853, University of New Mexico Center for Molecular Discovery, Chemical Pattern Detection and Visualization in Biological Networks