Novel analogs of tricyclic psychopharmacological agents

Abstract

The synthesis of several novel analogs of amitriptyline and chlorprothixene, in a number of which the position of the side-chain nitrogen atom rigidly fixed with respect to the tricyclic nucleus, is described. The compounds were evaluated for antidepressant-like activity in the Dopa and serotonin interaction tests and for potential antipsychotic activity in the methamphetamine interaction test. 5-(3-Dimethylaminocyclohex-1-enyl)-5H-dibenzo[a,d]cycloheptene (12) was about equipotent with imipramine in the Dopa and methamphetamine tests, and 3-chloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-spiro-6'-3'-methyl-3'-azabicyclo[3.1.0]hexane (23) also displayed marked activity in the same tests. Prototype compounds for other ring systems, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene tropane (16) and 5-(3-dimethylaminocycloheptylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (18), were less active.

Easy access to medium-sized lactones through metal carbene migratory insertion enabled 1,4-palladium shift

“…Diol 84 was converted to suberene 86 by using a consecutive DMP oxidation and TiCl 4 -mediated McMurry reaction protocol. To our delight, we found compound 86 has significant utility in preparing miscellaneous medicinally important molecules [49][50][51] . For example, cyproheptadine 87, an antihistaminic and antiserotonergic agent, could be prepared by following reported procedures in three steps 52,53 .…”

Synthesis of Novel γ-Aminobutyric Acid (GABA) Uptake Inhibitors. 5. Preparation and Structure−Activity Studies of Tricyclic Analogues of Known GABA Uptake Inhibitors

“…Two procedures for the preparation of these bromides were investigated, and the most convenient method found is a modification of a previously reported procedure . In this procedure, the appropriately substituted 10,11-dihydro-5H-dibenzo[ a , d ]cyclohepten-5-one , was reacted with vinylmagnesium bromide to give the corresponding substituted 5-ethenyl-10,11-dihydro-5H-dibenzo[ a , d ]cyclohepten-5-ols (i.e., 48 ). The reduced ketones, i.e., 10,11-dihydro-5H-dibenzo[ a , d ]cyclohepten-5-ols, were observed as byproducts in this Grignard reaction but in a much lower yield than if ethylmagnesium bromide were used instead of vinylmagnesium bromide.…”

“…The Two procedures for the preparation of these bromides were investigated, and the most convenient method found is a modification of a previously reported procedure. 68 In this procedure, the appropriately substituted 10,11dihydro-5H-dibenzo[a,d]cyclohepten-5-one 69,70 afforded the chain saturated acid hydrochloride 37. However, it was observed that the ether linkage of the starting allyl ether was partly cleaved during hydrogenation.…”