Structure-activity studies on antidepressant 2,2-diarylethylamines.

B E Maryanoff; S O Nortey; J F Gardocki

doi:10.1021/jm00374a022

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Structure-activity studies on antidepressant 2,2-diarylethylamines.

B E Maryanoff·S O Nortey·J F Gardocki

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Abstract

A series of 2,2-diarylethylamine derivatives has been examined for potential antidepressant activity in the tetrabenazine (TBZ) test. Diethanolamine 4 (McN-4187) was one of the more potent compounds despite its polar alcohol functionalities [ED50 values of 15 mg/kg (exploratory activity) and 1.5 mg/kg (ptosis)]. Structure-activity relationships are described. Minor structural modifications of 4 were sufficient to strongly attenuate activity. For example, changing one phenyl group to a 2-thienyl, cyclohexyl, or 3,4-dimethoxyphenyl group greatly reduced activity. Replacing both phenyl groups by 4-chlorophenyl groups also dissipated activity. The bisethanol functionality was not essential for activity (q.v. 17-19 in Table I). Although 17-19 compared well with 4 in the TBZ assay, only 19 (like 4) showed a satisfactory profile in the maximal electroshock seizure threshold test.

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Animals Antidepressive Agents Electroshock Ethanolamines Ethylamines Exploratory Behavior Male Mice Motor Activity Structure-Activity Relationship Tetrabenazine Journal Article

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B E Maryanoff, S O Nortey, J F Gardocki. 1984. Structure-activity studies on antidepressant 2,2-diarylethylamines.. https://doi.org/10.1021/jm00374a022

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