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

Abstract

10-(Alkylamino)thieno[3,4-b][1,5]benzoxazepines (3) and 10-(alkylamino)thieno[3,4-b][1,5]benzothiazepines (4) were prepared by derivatization of the respective lactams (7 and 8) via phosphorus pentachloride and subsequent condensation with the appropriate alkylamines. 9-(Alkylamino)-4H-thieno[3,4-b][1,4]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. Most of the title compounds 3-6 were found to have neuroleptic activity. In addition, introduction of a 3-chloro substituent in the oxygen and sulfur systems (3p and 4c), as well as introduction of an N-alkyl in the dinitrogen system (6), was found to produce antidepressant effects. Structure-activity relationships are discussed.

A Consecutive Four‐Component Synthesis of Polysubstituted Thiophenes in Aqueous Medium

“…Compounds with a thiophene scaffold have attracted considerable attention in organic and medicinal chemistry as they are the building blocks of many natural products and active pharmaceutical ingredients, such as Reloxifen, Raltitrexed, Duloxetine and Clopidogrel . They exhibit different biological effects, resulting in their extensive use as antidepressant, neuroleptic, photoactivated insecticidal and superagonist agents . Furthermore, these scaffolds play important roles in materials science and have been used in developing light‐emitting diodes, field‐effect transistors and solar cells due to their access and exclusive properties…”

Automated Potentiometric Titration Method for Determination of pKValues: An Application to Benzodiazepines

“…The simplest method for synthesis of these compounds involves the acid-catalyzed reaction of o -pheneylenediamine with ketones, β-haloketones, and α,β-unsaturated carbonyl compounds . In addition to 1,4-benzodiazepines, 1,5-benzodiazepines also act as central nervous system (CNS) depressants, − antianxiety agents, potential neuroleptics, potential antidepressants, and agonists and have psychotropic and pesticidal activity . 1,5-Benzodiazepines are key intermediates for some fused heterocyclic rings such as triaxol and oxadiazole.…”

Synthesis of thieno[2,3‐b][1,5]benzoxazepine derivatives

“…Benzothiazepine, benzoxazepine and benzodiazepine derivatives have desirable antipsychotic activities [1][2][3][4]. Investigations into the synthesis of these novel compounds and their biological activities may promote exciting progress in the medical field.…”