Discovery of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1H-1,2,4-triazole, a novel in vivo cannabinoid antagonist containing a 1,2,4-triazole motif

被引：69

作者：

Jagerovic, N

Hernandez-Folgado, L

Alkorta, I

Goya, P

Navarro, M

Serrano, A

de Fonseca, FR

Dannert, MT

Alsasua, A

Suardiaz, M

Pascual, D

Martín, MI

机构：

[1] CSIC, Inst Quim Med, E-28006 Madrid, Spain

[2] Univ Complutense Madrid, Dept Psicobiol, Fac Psicol, E-28040 Madrid, Spain

[3] Fdn Hosp Carlos Haya, E-29010 Malaga, Spain

[4] Univ Complutense Madrid, Fac Med, E-28040 Madrid, Spain

[5] Univ Rey Juan Carlos, Unidad Farmacol, Fac Ciencias Salud, E-28922 Madrid, Spain

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 11期

关键词：

D O I：

10.1021/jm031099y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of 1,2,4-triazoles have been prepared and the evaluation of their cannabinoid properties have been carried out. Compound 8 showed cannabinoid silent antagonist activity in mouse vas deferens and guinea pig ileum preparations and in vivo assays (cannabinoid tetrad) in mouse. It did not have intrinsic activity in these bioassays, and therefore, it did not behave as a partial agonist or an inverse agonist.

引用

收藏

页码：2939 / 2942

页数：4

相关论文

共 22 条

[1] Inhibition by cannabinoid receptor agonists of acetylcholine release from the guinea-pig myenteric plexus [J].

Coutts, AA ;

Pertwee, RG .

BRITISH JOURNAL OF PHARMACOLOGY, 1997, 121 (08) :1557-1566

[2] 1,2,4-TRIAZOLES .6. SYNTHESIS OF NEW 1,5-DIPHENYL-3-1H-1,2,4-TRIAZOLES SUBSTITUTED WITH H-, ALKYL, OR CARBOXYL GROUPS AT C-3 [J].

CZOLLNER, L ;

SZILAGYI, G ;

LANGO, J ;

JANAKY, J .

ARCHIV DER PHARMAZIE, 1990, 323 (04) :225-227

[3] From cannabis to cannabinergics: new therapeutic opportunities [J].

Goutopoulos, A ;

Makriyannis, A .

PHARMACOLOGY & THERAPEUTICS, 2002, 95 (02) :103-117

[4] Recent advances in cannabinoid receptor agonists and antagonists [J].

Goya, P ;

Jagerovic, N .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2000, 10 (10) :1529-1538

[5] Evidence for the presence of CB2-like cannabinoid receptors on peripheral nerve terminals [J].

Griffin, G ;

Fernando, SR ;

Ross, RA ;

McKay, NG ;

Ashford, MLJ ;

Shire, D ;

Huffman, JW ;

Yu, S ;

Lainton, JAH ;

Pertwee, RG .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 339 (01) :53-61

[6]

JAGEROVIC N, 2003, Patent No. 03682833

[7]

Lake KD, 1997, J PHARMACOL EXP THER, V281, P1030

[8] Persistently active cannabinoid receptors mute a subpopulation of hippocampal interneurons [J].

Losonczy, A ;

Biró, AA ;

Nusser, Z .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (05) :1362-1367

[9] Exploration of the pharmacophore of 3-alkyl-5-arylimidazolidinediones as new CB1 cannabinoid receptor ligands and potential antagonists:: Synthesis, lipophilicity, affinity, and molecular modeling [J].

Ooms, F ;

Wouters, J ;

Oscari, O ;

Happaerts, T ;

Bouchard, G ;

Carrupt, PA ;

Testa, B ;

Lambert, DM .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (09) :1748-1756

[10] Cannabinergic ligands [J].

Palmer, SL ;

Thakur, GA ;

Makriyannis, A .

CHEMISTRY AND PHYSICS OF LIPIDS, 2002, 121 (1-2) :3-19