SYNTHESIS OF SOME 2-ARYL-1,2,4-TRIAZOLO[1,5-C][1,3]BENZOXAZIN-5-ONES AS TOOLS TO DEFINE THE ESSENTIAL PHARMACOPHORIC DESCRIPTORS OF A BENZODIAZEPINE RECEPTOR-LIGAND

被引：24

作者：

CATARZI, D

CECCHI, L

COLOTTA, V

FILACCHIONI, G

VARANO, F

MARTINI, C

GIUSTI, L

LUCACCHINI, A

机构：

[1] UNIV FLORENCE,DIPARTIMENTO SCI FARMACEUT,I-50121 FLORENCE,ITALY

[2] UNIV PISA,IST POLICATTEDRA DISCIPLINE BIOL,I-56100 PISA,ITALY

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 12期

关键词：

D O I：

10.1021/jm00012a020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and benzodiazepine receptor (BZR) affinity of some 1,2,4-triazolo[1,5-c][1,3]benzoxazin-5-ones, 2-22, are reported. Compounds 2-22 are devoid of the proton donor group, which according to a BZR schematic model was one of the pharmacophoric descriptors for receptor-ligand interaction. The binding data show that 2-(2-fluorophenyl)-9-chloro-1,2,4-triazolo[1,5-c][1,3]benzoxazin-5-one (12) and some other compounds display nanomolar BZR affinity, indicating that the hydrogen donor group is not essential for the anchoring of 6,6,5-tricyclic systems to the BZR but only affects the potency of a ligand.

引用

页码：2196 / 2201

页数：6

共 29 条

[1]

Villar H.O., Davies M.F., Loew G.H., Maguire P.A., Molecular models for recognition and activation at benzodiazepine receptor: a review, Life Sci., 48, pp. 593-602, (1991)

[2]

Crippen G.M., Distance geometry analysis of the benzodiazepine binding site, Mol. Pharmacol., 22, pp. 11-19, (1982)

[3]

Fryer R.I., Ligand interactions at the benzodiazepine receptor, Comprehensive Medicinal Chemistry, 3, pp. 539-566, (1989)

[4]

Fryer R.I., Gu Z.-Q., Wang C.G., Synthesis of novel substituted 4H-imidazo[1, 5-a][1, 4]benzodiazepines, J. Heterocycl. Chem., 28, pp. 1661-1669, (1991)

[5]

Codding P.W., Muir A.K.S., Molecular structure of Ro 15-1788 and a model for binding of benzodiazepine receptor ligands, Mol. Pharmacol., 28, pp. 178-184, (1985)

[6]

Allen M.S., Hagen T.J., Trudell M.L., Codding P.W., Skolnick P., Cook J.M., Synthesis of novel 3-substituted β-carbolines as benzodiazepine receptor ligands: probing the benzodiazepine receptor pharmacophore, J. Med. Chem., 31, pp. 1854-1861, (1988)

[7]

Borea P.A., Gilli G., Bertolasi V., Ferretti V., Stereochemical features controlling binding and intrinsic activity properties of benzodiazepine-receptor ligands, Mol. Pharmacol., 31, pp. 334-344, (1987)

[8]

Tebib S., Bourguignon J.J., Wermuth C.G., The active analog approach applied to the pharmacophore identification of benzodiazepine receptor ligands, J. Comput-Aided Mol. Des, 1, pp. 153-170, (1987)

[9]

Villar H.O., Uyeno E.T., Toll L., Polgar W., Davies M.F., Loew G.H., Molecular determination of benzodiazepine receptor affinities and anticonvulsant activities, Mol. Pharmacol., 36, pp. 586-600, (1989)

[10]

Trudell M.L., Lifer S.L., Tan Y.-C., Martin M.J., Deng L., Skolnick P., Cook J.M., Synthesis of substituted 7, 12- dihydropyrido[3, 2-b: 5, 4-b’]diindoles: rigid planar benzodiazepine receptor ligands with inverse agonist/antagonist properties, J. Med. Chem., 33, pp. 2412-2420, (1990)

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