3-(Alkylamino)-4H-pyrido[4,3-e]1,2,4-thiadiazine 1,1-dioxides as powerful inhibitors of insulin release from rat pancreatic B-cells: a new class of potassium channel openers?

A potent diazoxide analogue activating ATP-sensitive K + channels and inhibiting insulin release

“…The BPDZ 73 ( Fig. 1) was obtained from the reaction of an excess of isopropylamine with 7-chloro-3-methylsulphanyl-4H-1,2,4-benzothiadiazine 1,1-dioxide, a useful synthetic intermediate in the access way to 3-alkylamino-substituted benzothiadiazine 1,1-dioxides [22,23]. The synthesis of the 3-methylsulphanyl-substituted intermediate was done in three steps starting from 4-chloroaniline and following methods described previously [24,27].…”

“…The proton NMR spectrum was taken on a Bruker AW-80 (80 MHz) instrument (Bruker, Karlsruhe, Germany). The compound was obtained as described previously for structural analogues [22,23] For the in vitro experiments, glibenclamide, diazoxide and BPDZ 73 were dissolved in dimethylsulphoxide which was added to both control and test media. At the final concentrations used, dimethylsulphoxide fails to affect islet function and smooth muscle contractility [17,21,26].…”

3-Benzamido-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-Dioxide

“…The title compound was synthesized as described by Pirotte et al (1993) at the laboratory of Medicinal Chemistry of Liege.…”

“…be regarded as an acyl derivative of recently reported 3-alkylaminopyridothiadiazine dioxides (Pirotte et al, 1993), known to be strong activators of the pancreatic ATP-sensitive potassium channel and structurally related to diazoxide [7-chloro-3-methyl-2H(or 4H)-1,2,4-benzothiadiazine 1,1-dioxide]. The particular interest of the present crystallographic study is to demonstrate which is the preferential tautomeric form adopted by the acyl derivative in the solid state: the 4H form (1) or the 2H form (2).…”

3-Methyl-4H-pyrido[4,3-e][1,2,4]thiadiazine 1,1-Dioxide Monohydrate

“…1974; Pirotte, de Tullio, Lebrun, Antoine, Fontaine, Masereel, Schynts, Dupont, Herchuelz & Delarge, 1993). The title compound (1) also contains this ring system and is related structurally to diazoxide [7-chloro-3-methyl-2H(or 4H)-1,2,4-benzothiadiazine 1,1-dioxide], a well known antihypertensive agent currently reported as the pharmacological reference for the benzothiadiazine class of ATP-sensitive potassium-channel openers (Edwards & Weston, 1990).…”