Using Physicochemical Measurements to Influence Better Compound Design. (September 2019)

• Record Type: Journal Article
• Authors: Bunally, Shenaz B.; Luscombe, Christopher N.; Young, Robert J.
• Is Part Of: SLAS discovery. Volume 24:Number 8(2019)
• Page Start: 791
• Page End: 801
• Publication Date: 2019-09
• Subjects: physicochemical properties -- lipophilicity -- property-based design -- chromatographic measurements; Drugs -- Analysis -- Periodicals; Drugs -- Testing -- Periodicals; Biomolecules -- Analysis -- Periodicals; Biomolecules -- Analysis; Drugs -- Analysis; Drugs -- Testing; Drug Evaluation, Preclinical; Molecular Biology -- methods; Periodicals; Periodicals; 615.1
• DOI: 10.1177/2472555219859845
• Languages: English
• ISSNs: 2472-5552

Abstract

During the past decade, the physicochemical quality of molecules under investigation at all stages of the drug discovery process has come under particular scrutiny. The issues associated with excessive lipophilicity and poor solubility in particular are many and varied, ranging from poor outcomes in screening campaigns to promiscuity, limited and/or poorly predictable pharmacokinetic exposure, and, ultimately, greater chances of clinical failure. In this review, contemporary methods to secure key measurements are described along with their relevance to understanding the behavior of molecules in environments pertinent to pharmacological activity. Together, the various measurements contribute to predictive models of both the physicochemical properties themselves and the outcomes they influence.