Substituted 3-amino-1,1-diaryl-2-propanols as potential antidepressant agents
| Autor: | Judith A. Clark, Michael S. G. Clark, Michael S. Hadley, Derek V. Gardner, Laramie Mary Gaster, Anwer Shah, David Miller |
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| Rok vydání: | 1979 |
| Předmět: |
Male
Reserpine Hydrochloride medicine.drug_class Guinea Pigs In Vitro Techniques Imipramine Body Temperature Propanolamines Mice Structure-Activity Relationship chemistry.chemical_compound Animal models of depression Drug Discovery Benzophenone medicine Anticholinergic Animals Hydrobromide Parasympatholytics Muscle Smooth Pupil Stereoisomerism Combinatorial chemistry Antidepressive Agents chemistry Molecular Medicine Antidepressant Amine gas treating Salivation Muscle Contraction medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 22:1373-1379 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Following the discovery that 3-(dimethylamino)-1,1-diphenyl-2-propanol hydrobromide (1) possesses potent reserpine-prevention activity in mice, a series of analogues of 1 was synthesized and evaluated as potential antidepressant agents. Several routes to analogues of 1 were evaluated, the most generally applicable of which was the regiospecific ring opening of a suitably functionalized 1,1-diaryl-2,3-epoxypropane (obtained in three stages from the corresponding benzophenone) with the appropriate amine. The more interesting compounds of the series were evaluated for their propensity to cause undesirable peripheral anticholinergic effects, all compounds tested being markedly less active than imipramine on this parameter. On the basis of its good activity in biochemical and pharmacological animal models of depression, together with its relative lack of anticholinergic side effects, 1-(3-chlorophenyl)-3-(dimethylamino)-1-phenyl-2-propanol hydrochloride (20, BRL 14342) was chosen for further evaluation. |
| Databáze: | OpenAIRE |
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