New bicyclic antidepressant agent. Synthesis and activity of napactadine and related compounds

Abstract

A number of N,N'-dialkylarylamidines were synthesized and evaluated for antidepressant activity. Several of these compounds were synthesized from the corresponding nitriles by a new method. Slight structural modification in the series caused a marked change in biological activity and led to compounds as active as imipramine. The arylacetamidine, N,N'-dimethyl-2-naphthaleneethanimidamide hydrochloride (33) (napactadine) was selected for clinical study. Forty-eight additional analogues of 33, including a number of N-alkylamidines, were prepared.

Imidazole-derived agonists for the neurotensin 1 receptor

“…Although the alternate method was fewer steps, its low yields and the high cost of 4-aminoquinoline building blocks made the longer method more preferred and practical for most cases of interest. In addition to standard Pinner conditions, which generally do not work well for cases involving sterically hindered benzonitriles, many amidine-forming conditions were attempted 15–20 for the generation of G . Conditions (h), although inefficient, were the best we found for this sterically and electronically disfavorable case.…”

Facile Synthesis of Bicyclic Amidines and Imidazolines from 1,2-Diamines

“…Amidines are regarded as organic superbases and have been widely employed as key intermediates in the synthesis of heterocyclic compounds . Amidines are also important in the pharmaceutical industry due to their unique biological properties . Synthesis of chiral amidines has attracted much attention from synthetic organic chemists due to the widespread applications of amidines in asymmetric synthesis.…”

Blue Light-Promoted Cross-Coupling of α-Diazo Esters with Isocyanides: Synthesis of Ester-Functionalized Ketenimines

“…An amidine structural motif is of high relevance for medicinal chemistry . A notable example related to this work is napactadine ( N , N ′-dimethyl-2-naphthaleneethanimidamide hydrochloride), an antidepressant agent . Amidines, bearing an ester substituent at the α-position, are a practically unknown class of compounds and could be of great interest for drug development.…”

“…17 A notable example related to this work is napactadine (N,N′dimethyl-2-naphthaleneethanimidamide hydrochloride), an antidepressant agent. 18 Amidines, bearing an ester substituent at the α-position, are a practically unknown class of compounds and could be of great interest for drug development. A few examples of these compounds were just recently synthesized using transition metal catalysis.…”