Imidazoline Derivatives with Antiarrhythmic Activity

Abstract

Imidazolinylmethyl derivatives of a number of bicyclic and tricyclic ring systems were prepared and studied for their effect on experimental cardiac arrhythmias. One of the bicyclic compounds, 3-phenyl-2,3,4,5-tetrahydro-l-benzazepine, obtained by means of a Schmidt reaction on 2-phenyl-3,4-dihydro-l-naphthalenone fol-

A New Synthesis of 5-Phenyl-2,3-dihydro- and 2,3,4,5-Tetrahydro-1H-2-benzazepin-1-ones

“…The structure of this substance was strongly supported by the n.m.r. spectrum, and fully substantiated by palladium-catalyzed hydrogenation to the tetrahydro derivative 10 (R = H ) identical to the minor product4 obtained from the Schmidt expansion of 4-phenyl-1-tetralone (2).…”

“…benzazepin-2-ones (2). With the possible exception of the acid-catalyzed cyclization of the acid chlorides of o-carboxycinnamonitriles (4), the other known 2-benzazepin syntheses (3,(5)(6)(7) did not appear to be readily adaptable to the preparation of 2 or derivatives thereof.…”

Novel tetracyclic imidazole derivatives: Synthesis, dynamic NMR study, and anti‐inflammatory evaluation

“…For many condensed non‐aromatic heterocycles with one heteroatom in the 7‐membered ring correlation between conformational properties and biological activities are studied. Detailed study of N ‐acylbenzazepines with interesting pharmacological properties [33], by dynamic NMR is an instructive case [34–36]. For dihydrobenz/ b /azepines thermodynamic parameters for conformation equilibria are determined by dynamic NMR [37, 38].…”

Heterocyclic diversity: The road to biological activity

“…This prompted us to consider that the molecule was too closely related to the tricyclics and thus to look at it from a different perspective. That is to say, if one envisions the dissociation of one of the benzene rings (as noted by the heavy arrow in Figure 26) from the morphanthridine ring system and then connects the same by a single bond to the 7 -membered ring, the result is a 3-phenyl-2,3,4,5-tetrahydro-l-benzazepine, and indeed this heterocycle could readily be synthesized from 2-phenyl-l-tetralone derivatives by a Schmidt ring expansion reaction followed by reduction [32,33]. Su-13, 197 was found to be several times more potent than Antistine as an antiarrhythmic in experimental animals.…”

“…The preparation of the novel N-substituted pyrimidines and quinazolines came about by the unexpected chance observation of the formation in quantitative yield of a thiopyrimidine from the condensation of ethyl ~-anilinocrotonate with benzoylisothiocyanate [32] (Figure 32). Similarly, the enamine, anilinocyclohexene reacted with benzoylisothiocyanate to yield the tetrahydroquinazoline derivative ( Figure 33).…”