Arylpiperazines are nonselective agents that bind at 5-HT3 serotonin receptors with moderate to high affinity, whereas 1-phenylbiguanide is a low-affinity but more selective 5-HT3 agonist. In an attempt to enhance the affinity of the latter agent, and working with the assumption that similarities might exist between the binding of the two types of agents, we formulated structure-activity relationships for the binding of the arylpiperazines and then incorporated those substituents, leading to high affinity for the arylpiperazines, into 1-phenylbiguanide. A subsequent investigation examined the structure-activity relationships of the arylbiguanides and identified arylguanidines as a novel class of 5-HT3 ligands. Although curious similarities exist between the structure-activity relationships of the arylpiperazines, arylbiguanides, and arylguanidines, it cannot be concluded that all three series of compounds are binding in the same manner. Furthermore, upon investigating pairs of compounds in the three series, the arylpiperazines behaved as 5-HT3 antagonists (von Bezold-Jarisch assay) whereas the arylbiguanides and arylguanidines acted as 5-HT3 agonists.

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The structural requirements for decreasing cholesterol and triglyceride levels remain largely uninvestigated. Thus a systematic investigation of certain N-substituted dibenz[c,e]azepines is necessary. Twenty-four compounds of certain new N-substituted derivatives of dibenz[c,e]azepines-5,7-diones were synthesized and tested for their anticholestesrolemic and antitriglyceridimic activities. The evaluation of antihyperlipidemic activity of dibenz[c,e]azepine-5,7-diones (VII, X-XII) against Triton-WR1339-induced hyperlipidemia in rats showed a significant lowering of serum total cholesterol and triglyceride levels at a dose of 150 mg/kg compared with the control value. The phenyl substituted derivatives of diphenimide have shown a pronounced decrease in both triglyceride and cholesterol levels.