Synthesis of 10‐(4‐methyl‐1‐piperazinyl)thieno[3,2‐b][1,5]benzothiazepines

Abstract

A series of the title compounds has been synthesized by two alternative methods in order to study their potential neuroleptical activity and to compare it with the pharmacological data already obtained for compounds of other isomeric or related series.

Reactions of 2,3‐dihydro‐1H‐1,5‐benzodiazepines and chloroacetyl chlorides: Synthesis of 2a,3,4,5‐tetrahydro‐azeto [1,2‐a][1,5] benzodiazepin‐1(2H)‐ones

“…Only one enantiomer was obtained as the product in the cycloaddition reaction. The result is well consistent with their sulfur analogues, 2a,4-disubstituted 2-chloro-2,2a,3,4-tetrahydro-1H-azeto[2,1-d] [1,5] benzothiazepin-1-ones [8].…”

“…In 1 H NMR spectra of 3a-f, ␤-lactam benzodiazepine derivatives showed a characteristic singlet of the azetidinone ring proton at 4.94-5.07 ppm, and SCHEME 1 Synthesis of 2a,4-disubstituted 5-benzoyl-2chloro/2,2-dichloro-2a,3,4,5-tetrahydro-azeto[1,2-a] [1,5]benzodiazepin-1(2H )-ones 3a -h. SCHEME 2 Stereospecificity in cycloaddition reaction. signals of the diazepine CHCH 2 protons, in most cases, were of the ABX coupling system and shifted upfield.…”

“…In recent years, numerous benzodiazepine tricyclic derivatives have been synthesized, and their stereostructures have been studied because of their biological and pharmaceutical importance [1][2][3][4][5][6][7][8][9][10]. Until now, only a few examples of the ␤-lactam derivatives of benzoxazepines, benzothiazepines, and benzodiazepines have been published [11][12][13].…”

Involvement of covalent interactions in the mode of action of PPARβ/δ antagonists

“…58 In a chemical context, it has been shown that 3-halothiophene-2-carboxylates may undergo nucleophilic aromatic substitution with thiolates, 68 although these reactions proceed in higher yields with added copper metal or with the corresponding benzothiophenes as substrates (Scheme 1B). 69,70 Furthermore, the reactivity of electron-poor arylsulfonamides, such as nitrobenzenesulfonamides towards thiolates, has been studied and exploited in the synthetic preparation of the corresponding aminesa reaction that also produces 2-or 4-nitrophenylsuldes through a nucleophilic aromatic substitution mechanism (Scheme 1C). [71][72][73][74][75] In summary, we found it prudent to consider the possibility that the methyl 3-sulfamoylthiophene-2-carboxylate head group of GSK0660 (3) could be reactive towards a nucleophilic cysteine residue.…”