title: Design, synthesis, computational and biological evaluation of new anxiolytics.
abstract: New anxiolytics have been discovered by prediction of biological activity with computer programs pass and derek for a heterogeneous set of 5494 highly chemically diverse heterocyclic compounds (thiazoles, pyrazoles, isatins, a-fused imidazoles and others). The majority of tested compounds exhibit the predicted anxiolytic effect. The most potent activity was found in 2-(4-nitrophenyl)-3-(4-phenylpiperazinomethyl)imidazo[1,2-a]pyridine 8, 1-[(4-bromophenyl)-2-oxoethyl]-3-(1,3-dioxolano)-2-indolinone 3, 5-hydroxy-3-methoxycarbonyl-1-phenylpyrazole 5 and 2-(4-fluorophenyl)-3-(4-methylpiperazinomethyl)imidazo[1,2-a]pyridine 7. The application of the computer-assisted approach significantly reduced the number of synthesized and tested compounds and increased the chance of finding new chemical entities (NCEs).
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Chemistry, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece. geronik@pharm.auth.gr
authors.forename: Athina
authors.initials: A
authors.lastname: Geronikaki
authors.forename: Eugeni
authors.initials: E
authors.lastname: Babaev
authors.forename: John
authors.initials: J
authors.lastname: Dearden
authors.forename: Wim
authors.initials: W
authors.lastname: Dehaen
authors.forename: Dmitrii
authors.initials: D
authors.lastname: Filimonov
authors.forename: Irina
authors.initials: I
authors.lastname: Galaeva
authors.forename: Valentina
authors.initials: V
authors.lastname: Krajneva
authors.forename: Alexey
authors.initials: A
authors.lastname: Lagunin
authors.forename: Fliur
authors.initials: F
authors.lastname: Macaev
authors.forename: Guenadiy
authors.initials: G
authors.lastname: Molodavkin
authors.forename: Vladimir
authors.initials: V
authors.lastname: Poroikov
authors.forename: Serghei
authors.initials: S
authors.lastname: Pogrebnoi
authors.forename: Victor
authors.initials: V
authors.lastname: Saloutin
authors.forename: Alla
authors.initials: A
authors.lastname: Stepanchikova
authors.forename: Eugenia
authors.initials: E
authors.lastname: Stingaci
authors.forename: Natalia
authors.initials: N
authors.lastname: Tkach
authors.forename: Liudmila
authors.initials: L
authors.lastname: Vlad
authors.forename: Tatiana
authors.initials: T
authors.lastname: Voronina
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019295:Computational Biology; D003198:Computer Simulation; D015195:Drug Design; D005103:Expert Systems; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D007858:Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D006571:Heterocyclic Compounds