title: Bioisosteric matrices for ligands of serotonin receptors.
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.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków (Poland).
authors.forename: Dawid
authors.initials: D
authors.lastname: Warszycki
authors.forename: Stefan
authors.initials: S
authors.lastname: Mordalski
authors.forename: Jakub
authors.initials: J
authors.lastname: Staroń
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
mesh_terms: D015195:Drug Design; D006801:Humans; D008024:Ligands; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology
chemical_list: D008024:Ligands; D011725:Pyridines; D011985:Receptors, Serotonin; D054852:Small Molecule Libraries; D013449:Sulfonamides
keywords: bioisosteric matrices; bioisosteric substitutions; bioisosterism; chemical space; serotonin receptors