42140-68-1

Upstream product

• 186581-53-3 diazomethane 
• 40009-27-6 7-chloro-1,1-dioxo-1,4-dihydro-2H-1λ⁶-benzo[1,2,4]thiadiazine-3-thione 
• 74-88-4 methyl iodide 
• 40009-41-4 7-chloro-3-(methylsulfanyl)-4H-1,2,4-benzothiadiazine 1,1-dioxide 
• 5800-59-9 7-chloro-2,3-dihydro-3-oxo-4H-1,2,4-benzothiadiazine 
• 40009-27-6 7-chloro-3-thioxo-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide 
• 106-47-8 4-chloro-aniline 
• 40009-41-4 7-Chlor-3-methylmerkapto-2H-1,2,4-benzothiadiazin-1,1-dioxid 

Relevant academic research and scientific papers

Toward tissue-selective pancreatic B-cells KATP channel openers belonging to 3-alkylamino-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides

3-(Alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides were synthesized, and their activity on rat-insulin-secreting cells and rat aorta rings was compared to that of the KATP channel activators diazoxide and pinacidil. Structure-activity relationships indicated that an improved potency and selectivity for the pancreatic tissue was obtained by introducing a fluorine atom in the 7-position and a short linear (preferably ethyl) or cyclic (preferably cyclobutyl) hydrocarbon chain on the nitrogen atom in the 3-position. By contrast, strong myorelaxant activity was gained by the introduction of a halogen atom different from the fluorine atom in the 7-position and a bulky branched alkylamino chain in the 3-position. Thus, 3-(ethylamino)-7-fluoro-4H-1,2,4-benzothiadiazine 1,1-dioxide (11) expressed a marked inhibitory activity on pancreatic B-cells (IC50 = 1 μM) associated with a weak vasorelaxant effect (ED50 > 300 μM), whereas 7-chloro-3-(1,1-dimethylpropyl)amino-4H-1,2,4-benzothiadiazine 1,1-dioxide (27), which was only slightly active on insulin-secreting cells (IC50 > 10 μM), was found to be very potent on vascular smooth muscle cells (ED50 = 0.29 μM). Radioisotopic and electrophysiological investigations performed with 7-chlorinated, 7-iodinated, and 7-fluorinated 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides confirmed that the drugs activated KATP channels. The present data revealed that subtle structural modifications of 3-(alkylamino)-7-halo-4H-1,2,4-benzothiadiazine 1,1-dioxides can generate original compounds activating KATP channels and exhibiting different in vitro tissue selectivity profiles.

1,2,4-benzothiadiazine derivatives, their preparation and use

1,2,4-Benzothiadiazine derivatives represented by formula wherein D, R1, R2, R3, R4, R5, R12, R13, R14, R15 are defined in the description, composition thereof and methods for preparing the compounds are described.The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.