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ChemMedChem. 2015 Apr;10(4):601-5. doi: 10.1002/cmdc.201402563. Epub 2015 Mar 13.

Bioisosteric matrices for ligands of serotonin receptors.

Author information

1
Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków (Poland).

Abstract

The concept of bioisosteric replacement matrices is applied to explore the chemical space of serotonin receptor ligands, aiming to determine the most efficient ways of manipulating the affinity for all 5-HT receptor subtypes. Analysis of a collection of over 1 million bioisosteres of compounds with measured activity towards serotonin receptors revealed that an average of 31 % of the ligands for each target are mutual bioisosteres. In addition, the collected dataset allowed the development of bioisosteric matrices-qualitative and quantitative descriptions of the biological effects of each predefined type of bioisosteric substitution, providing favored paths of modifying the compounds. The concept exemplified here for serotonin receptor ligands can likely be more broadly applied to other target classes, thus representing a useful guide for medicinal chemists designing novel ligands.

KEYWORDS:

bioisosteric matrices; bioisosteric substitutions; bioisosterism; chemical space; serotonin receptors

PMID:
25772514
PMCID:
PMC4471634
DOI:
10.1002/cmdc.201402563
[Indexed for MEDLINE]
Free PMC Article

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