The significance of acid/base properties in drug discovery

David Thomas Manallack, Richard John Prankerd, Elizabeth Yuriev, Tudor I Oprea, David Kenneth Chalmers

Research output: Contribution to journalArticleResearchpeer-review

118 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)485 - 496
Number of pages12
JournalChemical Society Reviews
Volume42
Issue number2
DOIs
Publication statusPublished - 2013

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