ChemInform Abstract: SYNTHESIS AND ANTIARRHYTHMIC ACTIVITY OF NEW BENZOFURAN DERIVATIVES

Abstract

Die Ketone (I) liefern über die Oxime (II) die Acetamide (III), deren Umwandlung in Aminoalkylether (V), (VII) und (X) gemäß Formelschema erfolgt.

Thiophene systems. 5. Thieno[3,4-b][1,5]benzoxazepines, thieno[3,4-b][1,5]benzothiazepines, and thieno[3,4-b][1,4]benzodiazepines as potential central nervous system agents

“…Press,* Corris M. Hofmann, Nancy H. Eudy, Ivana P. Day, Eugene N. Greenblatt, and Sidney R. Safir Cardiovascular-CNS Disease Research Section, Medical Research Division of American Cyanamid Company, Lederle Laboratories, Pearl River, New York 10965. Received August 4,1980 10-(Alkylamino)thieno [3,4-b][l,5]benzoxazepines (3) and 10-(alkylamino)thieno [3,[4][5][6] [l,5]benzothiazepines (4) were prepared by derivatization of the respective lactams (7 and 8) via phosphorus pentachloride and subsequent condensation with the appropriate alky lamines. 9-(Alkylamino)-4fl-thieno [3,[4][5][6] [l,4]benzodiazepines (5) were prepared by titanium tetrachloride catalyzed condensation of the lactam 11 with alkylamines.…”

“…Received August 4,1980 10-(Alkylamino)thieno [3,4-b][l,5]benzoxazepines (3) and 10-(alkylamino)thieno [3,[4][5][6] [l,5]benzothiazepines (4) were prepared by derivatization of the respective lactams (7 and 8) via phosphorus pentachloride and subsequent condensation with the appropriate alky lamines. 9-(Alkylamino)-4fl-thieno [3,[4][5][6] [l,4]benzodiazepines (5) were prepared by titanium tetrachloride catalyzed condensation of the lactam 11 with alkylamines. 9-(Alkylamino)-4-methylthieno [3,4-b] [ 1,4]benzodiazepines (6) were prepared by reductive alkylation of 5. The compounds were tested for potential neuroleptic activity by means of the blockade of d-amphetamine lethality in aggregated mice and/or effects on locomotor activity in rats.…”

“…9-(Alkylamino)-4fl-thieno [3,[4][5][6] [l,4]benzodiazepines (5) were prepared by titanium tetrachloride catalyzed condensation of the lactam 11 with alkylamines. 9-(Alkylamino)-4-methylthieno [3,4-b] [ 1,4]benzodiazepines (6) were prepared by reductive alkylation of 5. The compounds were tested for potential neuroleptic activity by means of the blockade of d-amphetamine lethality in aggregated mice and/or effects on locomotor activity in rats. Antidepressant activity was examined using inhibition of tetrabenazine-induced depression in mice.…”

“…A previous report2 from these laboratories discussed the synthesis and biological properties of 10-(alkylamino)-4ifthieno [3,4-b] [l,5]benzodiazepines (1 and 2) as a novel class 1, R, = H 2, R, = alkyl Chart I. Preparation of Thieno [ 3,4-b ] [ 1,5 ]benzoxapines (3) and Thieno [3,4-b ][ 1,5]benzothiazepines (4) HN NR/PhCHj/ / \ 5, R = H 6, R = CH, of compounds with an interesting CNS profile. Encouraged by these results, we undertook further studies to prepare the 3,4-thieno analogues of loxapine3 and clothi-apine3 (3 and 4), as well as other analogues of clozapine,4 namely 5 and 6, with the hope of discovering new CNS agents with improved therapeutic profiles or with mixed action effects as we reported for 2.…”

“…Based on the structure-activity relationships observed previously,2 only piperazine substitutions at C-10 were investigated. In the thieno [3,[4][5][6] [ 1,5]benzoxazepines (3), -methylor IV-ethylpiperazinyl substituents (3a,b,d,e,g,i,k,l,n,p) produce the most potent neuroleptic activity. As a consequence, our major efforts were directed toward IV-alkylpiperazine derivatives for 4-6. More careful examination of the data for 3 (Table I) reveals that substitution of the aromatic nucleus at C-7 with methyl (3d,e), chlorine (3k,1), or bromine (3n) has little effect on neuroleptic activity compared to the allhydrogen system (3a,b).…”