SELECTIVE INHIBITORS OF MONOAMINE-OXIDASE (MAO) - 5 - 1-SUBSTITUTED PHENOXATHIIN INHIBITORS CONTAINING NO NITROGEN THAT INHIBIT MAO-A BY BINDING IT TO A HYDROPHOBIC SITE

It is believed that a monoamine oxidase (MAO) inhibitor specific for M AO A, which is reversibly bound to this enzyme and displaceable:by tyr amine, will be an antidepressant which will not cause a rise in blood pressure when tyramine-containing foods are ingested. Some linear tric yclic compounds with a larger and a smaller group forming the central ring and with a lipophilic group ortho to the larger group (here mostl y the SO2 function of phenoxathiin 10, -10-dioxide) are reported to ha ve the sought properties. Potency appears to require short length and relatively small cross section for the substituent. The 1-ethyl (13), 1-vinyl (22), 1-trifluoromethyl (27), and 1-iodo (76) phenoxathiin dio xides had the best profiles. Structure-activity relationships, synthes es, and a possible rationale for the selectivity of these compounds an d related tricyclics are given. Compound 13 was selected for further d evelopment. A summary of pharmacological data for 13 is given.