2-benzazepines. 5. Synthesis of pyrimido[5,4-d][2]benzazepines and their evaluation as anxiolytic agents

E J Trybulski; L E Benjamin Sr; J V Earley; R I Fryer; N W Gilman; E Reeder; A Walser; A B Davidson; W D Horst; J Sepinwall

doi:10.1021/jm00365a008

2-benzazepines. 5. Synthesis of pyrimido[5,4-d][2]benzazepines and their evaluation as anxiolytic agents

J Med Chem. 1983 Nov;26(11):1589-96. doi: 10.1021/jm00365a008.

Authors

E J Trybulski, L E Benjamin Sr, J V Earley, R I Fryer, N W Gilman, E Reeder, A Walser, A B Davidson, W D Horst, J Sepinwall, et al.

PMID: 6138436
DOI: 10.1021/jm00365a008

Abstract

A series of 5H-pyrimido[5,4-d][2]benzazepines has been synthesized, starting from the corresponding 2-benzazepin-5-ones, and evaluated as potential anxiolytic agents. Selected compounds from this series show a pharmacological profile of action different than that of diazepam. They are more potent than diazepam in the anti-pentylenetetrazole test and in the [3H]diazepam binding assay, yet show less activity in the inclined screen test. A pharmacological data profile is given for 9-chloro-7-(2-chlorophenyl)-5H-pyrimido[5,4-d] [2]benzazepine (7c). The structure-activity relationships of these potential anxiolytic agents are discussed.

Publication types

Comparative Study

MeSH terms

Animals
Anti-Anxiety Agents / chemical synthesis*
Benzazepines / chemical synthesis*
Benzazepines / pharmacology
Biological Assay
Diazepam / metabolism
Drug Evaluation, Preclinical
Drug Interactions
Ethanol / pharmacology
Indicators and Reagents
Magnetic Resonance Spectroscopy
Male
Mice
Motor Activity / drug effects
Pyrimidines / chemical synthesis
Pyrimidines / pharmacology
Receptors, Cell Surface / drug effects
Receptors, Cell Surface / metabolism
Receptors, GABA-A
Reflex / drug effects
Spectrophotometry, Infrared
Structure-Activity Relationship

Substances

Anti-Anxiety Agents
Benzazepines
Indicators and Reagents
Pyrimidines
Receptors, Cell Surface
Receptors, GABA-A
Ethanol
Diazepam