A novel class of potential central nervous system agents. 3-Phenyl-2-(1-piperazinyl)-5H-1-benzazepines

Abstract

A series of 3-phenyl-2-piperazinyl-5H-1-benzazepines and related compounds were synthesized and evaluated for potential neuroleptic activity. The preparation of these compounds was carried out by 2,3-dichlorination of 3-phenyl-2,3,4,5-tetrahydro-1H-1-benzazepin-2-ones with phosphorus pentachloride followed by amination and concurrent dehydrochlorination. Compounds having the 4-chloro or 4-fluoro substituent in the 3-phenyl group were found to possess the neuroleptic-like activity. Among them, 2-(4-methyl-1-piperazinyl)-3-(4-fluorophenyl)-5H-1-benzazepine dihydrochloride (23) was comparable to chlorpromazine in inhibiting exploratory activity, conditioned avoidance response, and self-stimulation response and more potent than chlorpromazine in antagonizing apomorphine-induced emesis. These neuroleptic effects may be based on an antidopaminergic property of the compound. In causing catalepsy or ptosis, however, 23 was weaker than chlorpromazine. Therefore, this ring system is of interest as a novel class of neuroleptics. Some compounds having the 7-chloro or 7-bromo substituent showed potent anticonvulsant effects against maximal seizures induced by electroshock or pentylenetetrazole.

An efficient and mild protocol for the α-arylation of ketones mediated by an (imidazol-2-ylidene)palladium(acetate) system

“…2-p-Tolyl-cyclohexanone [34] (Table 5, entry 1): The procedure afforded 126 mg (67%) of the compound. 2-p-Tolyl-3,4-dihydro-2H-naphthalen-1-one [35] (Table 5, entry 6): The procedure afforded 196 mg (83%) of the compound.…”

α-Trifluoromethyl Chalcones as Potent Anticancer Agents for Androgen Receptor-Independent Prostate Cancer

“…The novel α-trifluoromethyl chalcones ( 2 – 7 ) and known 1 [ 12 ] , were synthesized from the related chalcones [ 13 , 14 , 15 , 16 ] including novel 10 and 11 , which were obtained by Claisen-Schmidt condensation of aryl methyl ketones and aromatic aldehydes. In target compounds 1 – 7 , the aromatic aldehyde was either unsubstituted or substituted with one of three electron withdrawing groups (F, CF 3 , or NO 2 ) or an electron donating group (NMe 2 ) for comparative purposes.…”

Inhibitors of Acyl CoA:Cholesterol Acyltransferase

“…Cis amides of 4 − 7 were derived from ketones 8 − 11 as shown in Scheme . In method 5, ketones 9 or 11 were converted to the corresponding oximes 18 with hydroxylamine . Treatment of 18 with diphenylphosphoryl chloride at low temperature presumably phosphorylates the oxime oxygen first; upon warming a phosphorus O to N rearrangement occurs to provide the phosphinylimine 19 .…”