Improvement in aqueous solubility achieved via small molecular changes. Issue 23 (1st December 2017)

• Record Type: Journal Article
• Authors: Walker, Michael A.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 27:Issue 23(2017)
• Page Start: 5100
• Page End: 5108
• Publication Date: 2017-12-01
• Subjects: Aqueous solubility -- Drug properties -- General Solubility Equation (GSE) -- Hydrophobicity -- Physicochemical properties; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.09.041
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Overcoming poor solubility is a significant issue in drug discovery. The most common solution is to replace carbon atoms with polar heteroatoms such as N and O or by attaching a solubilizing appendage. This approach can lead to other issues such as poor activity and PK or the increased risk for toxicity. However, there are more subtle structural changes which can be employed that lead to an increase in solubility. These include, excising hydrophobic groups which do not efficiently contribute to binding, modifying stereo- and regiochemistry, increasing or decreasing the degree of unsaturation or adding small hydrophobic groups such as fluorine or methyl.