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

Dupont, L.; Tullio, Pascal De; Pirotte, Bernard; Masereel, Bernard; Delarge, J.

doi:10.1107/s0108270194013235

Cited by 2 publications

(3 citation statements)

References 4 publications

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“…It was found that the N(2)-C(3) length (1.315 Å) of compound 34 was shorter than its C(3)-N( 4) length (1.366 Å), supporting the view that the CdN double bond of the thiadiazine ring is preferentially located in the 2,3-positions corresponding for 34 to the adoption of a 4H-tautomeric form. Such a preferred conformation has already been observed with diazoxide 27 and with previously reported 3-alkylpyridothiadiazines 26,28,29 in the solid state.…”

Section: Resultssupporting

confidence: 81%

3- and 4-Substituted 4H-Pyrido[4,3-e]-1,2,4-thiadiazine 1,1-Dioxides as Potassium Channel Openers: Synthesis, Pharmacological Evaluation, and Structure−Activity Relationships

et al. 1996

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4-N-Substituted and -unsubstituted 3-alkyl- and 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides were synthesized and tested vs diazoxide and selected 3-alykl- and 3-(alkylamino)-7-chloro-4H-1,2,4-benzothiadiazine 1,1-dioxides as potassium channel openers on pancreatic and vascular tissues. Several 4-N-unsubstituted 3-(alkylamino)pyridothiadiazines and some 3-(alkylamino)-7-chlorobenzothiadiazines were found to be more potent than diazoxide for the inhibition of the insulin-releasing process. Moreover, the 3-(alkylamino)pyridothiadiazines appeared to be more selective for the pancreatic than for the vascular tissue. By means of the pharmacological results obtained on pancreatic B-cells, structure--activity relationships were deduced and a pharmacophoric model for the interaction of these drugs with their receptor site associated to the pancreatic K(ATP) channel was proposed. According to their selectivity for the B-cell (endocrine tissue) vs the vascular (smooth muscle tissue) ionic channel, selected 3-(alkylamino)-4H-pyrido[4,3-e]-1,2,4,-thiadiazine 1,1-dioxides may serve as pharmacological tools in studying the K(ATP) channels ("pancreatic-like" K(ATP) channels) in other tissues.

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Section: Resultssupporting

confidence: 81%

3- and 4-Substituted 4H-Pyrido[4,3-e]-1,2,4-thiadiazine 1,1-Dioxides as Potassium Channel Openers: Synthesis, Pharmacological Evaluation, and Structure−Activity Relationships

et al. 1996

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“…The 1,2,4-thiadiazine rings of 1a and 2 are planar within experimental error. Thus, the structures of compounds 1a and 2 in the solid state are analogous to those found for other K ATP COs of the 1,2,4-pyridothiadiazine 1,1-dioxide − and the 1,2,4-benzothiadiazine 1,1-dioxide (e.g., diazoxide) types. For 1a , 2 , and diazoxide it is not possible to uniquely establish the 4H- or 2H-tautomerism by 1 H NMR spectroscopy, since there are no signals from neighboring atoms.…”

Section: Chemistrysupporting

confidence: 57%

“…In form B of 2, which represents a solvate in a rhombohedral crystal modification with one molecule in the asymmetric unit, 2 is also a 4H-tautomer and the thiophene and the thiadiazine rings are coplanar. The planar ring system is another characteristic of the pyridothiadiazine 1,1-dioxide [24][25][26][27] and the benzothiadiazine 1,1-dioxide 28 molecules in the solid state. This is in contrast to pinacidil in the solid state where the guanidine moiety plane is twisted approximately 40°from the plane of the pyridine group.…”

Section: Chemistrymentioning

confidence: 99%

New 3-Alkylamino-4H-thieno-1,2,4-thiadiazine 1,1-Dioxide Derivatives Activate ATP-Sensitive Potassium Channels of Pancreatic Beta Cells

et al. 2006

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Compound 1a (NN414) is a potent opener of Kir6.2/SUR1 K(ATP) channels. Compound 1a inhibits insulin release in vitro and in vivo and preserves beta cell function in preclinical animal models suggesting that such a compound could find use in treatment or prevention of type 1 and type 2 diabetes. The crystal structure and a convergent synthesis of 1a are presented together with a range of new analogues of 1a. Several compounds, e.g., 6-chloro-3-(1-methyl-1-phenylethyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1h), were found to be potent openers of Kir6.2/SUR1 K(ATP) channels and were able to suppress glucose-stimulated insulin release from rat islets in vitro (EC(50) = 0.04 +/- 0.01 muM) and in vivo after intravenous or peroral administration to hyperinsulinemic obese Zucker rats (ED(50) = 4.0 mg/kg). Structural modifications of this series of K(ATP) channel openers have provided compounds with promising pharmacokinetic properties indicating that brief periods of beta cell rest can be achieved.

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

Cited by 2 publications

References 4 publications

3- and 4-Substituted 4H-Pyrido[4,3-e]-1,2,4-thiadiazine 1,1-Dioxides as Potassium Channel Openers: Synthesis, Pharmacological Evaluation, and Structure−Activity Relationships

3- and 4-Substituted 4H-Pyrido[4,3-e]-1,2,4-thiadiazine 1,1-Dioxides as Potassium Channel Openers: Synthesis, Pharmacological Evaluation, and Structure−Activity Relationships

New 3-Alkylamino-4H-thieno-1,2,4-thiadiazine 1,1-Dioxide Derivatives Activate ATP-Sensitive Potassium Channels of Pancreatic Beta Cells

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