Design, synthesis, computational and biological evaluation of new anxiolytics

被引：128

作者：

Geronikaki, A ^{[1
]}

Babaev, E

Dearden, J

Dehaen, W

Filimonov, D

Galaeva, I

Krajneva, V

Lagunin, A

Macaev, F

Molodavkin, G

Poroikov, V

Pogrebnoi, S

Saloutin, V

Stepanchikova, A

Stingaci, E

Tkach, N

Vlad, L

Voronina, T

机构：

[1] Aristotle Univ Thessaloniki, Dept Pharmaceut Chem, Sch Pharm, Thessaloniki 54124, Greece

[2] Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119899, Russia

[3] Liverpool John Moores Univ, Sch Pharm & Chem, Liverpool L3 3AF, Merseyside, England

[4] Catholic Univ Louvain, B-3001 Louvain, Belgium

[5] Russian Acad Med Sci, Inst Biomed Chem, Moscow 119121, Russia

[6] Russian Acad Med Sci, Inst Pharmacol, Moscow 125315, Russia

[7] Moldavian Acad Sci, Inst Chem, MD-2028 Kishinev, Moldova

[8] Russian Acad Sci, Inst Organ Chem, Urals Div, Ekaterinburg 620219, Russia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 24期

关键词：

anxiolytics; synthesis; thiazoles; pyrazoles; 2-indolinones; fused imidazoles; PASS;

D O I：

10.1016/j.bmc.2004.09.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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, 5hydroxy-3-methoxycarbonyl-l-phenylpyrazole 5 and 2-(4-fluorophenyl)-3-(4-methylpiperazinomethyl)imidazo[1,2-cr]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). circle dot 2004 Elsevier Ltd. All rights reserved.

引用

页码：6559 / 6568

页数：10

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