Design, synthesis, computational and biological evaluation of new anxiolytics.
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).
Geronikaki
Athina
A
School of Pharmacy, Department of Pharmaceutical Chemistry, Aristotelian University of Thessaloniki, Thessaloniki 54124, Greece. geronik@pharm.auth.gr
Babaev
Eugeni
E
Dearden
John
J
Dehaen
Wim
W
Filimonov
Dmitrii
D
Galaeva
Irina
I
Krajneva
Valentina
V
Lagunin
Alexey
A
Macaev
Fliur
F
Molodavkin
Guenadiy
G
Poroikov
Vladimir
V
Pogrebnoi
Serghei
S
Saloutin
Victor
V
Stepanchikova
Alla
A
Stingaci
Eugenia
E
Tkach
Natalia
N
Vlad
Liudmila
L
Voronina
Tatiana
T
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
D014151:Anti-Anxiety Agents; D006571:Heterocyclic Compounds