279215-43-9

Basic information

• Product Name: 8-chloro-N-(1-methylcyclopropyl)-2,2-dioxo-2$l^{6},9-dithia-3,5-diazab icyclo[4.3.0]nona-3,7,10-trien-4-amine
• Synonyms: 8-chloro-N-(1-methylcyclopropyl)-2,2-dioxo-2$l^{6},9-dithia-3,5-diazab icyclo[4.3.0]nona-3,7,10-trien-4-amine;tifenazoxide;6-Chloro-3-[[1-methylcyclopropyl]amino]-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide;NN414
• CAS NO: 279215-43-9
• Molecular Formula: C₉H₁₀ClN₃O₂S₂
• Molecular Weight: 291.78
• Mol File: 279215-43-9.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 448°Cat760mmHg
• Flash Point: 224.7°C
• Appearance: white to beige/
• Density: 1.88g/cm³
• Vapor Pressure: 3.22E-08mmHg at 25°C
• Refractive Index: 1.831
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble15mg/mL, clear
• CAS DataBase Reference: 8-chloro-N-(1-methylcyclopropyl)-2,2-dioxo-2$l^{6},9-dithia-3,5-diazab icyclo[4.3.0]nona-3,7,10-trien-4-amine(CAS DataBase Reference)
• NIST Chemistry Reference: 8-chloro-N-(1-methylcyclopropyl)-2,2-dioxo-2$l^{6},9-dithia-3,5-diazab icyclo[4.3.0]nona-3,7,10-trien-4-amine(279215-43-9)
• EPA Substance Registry System: 8-chloro-N-(1-methylcyclopropyl)-2,2-dioxo-2$l^{6},9-dithia-3,5-diazab icyclo[4.3.0]nona-3,7,10-trien-4-amine(279215-43-9)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 279215-43-9(Hazardous Substances Data)

Usage

InChI:InChI=1/C9H10ClN3O2S2/c1-9(2-3-9)12-8-11-5-4-6(10)16-7(5)17(14,15)13-8/h4H,2-3H2,1H3,(H2,11,12,13)

Upstream product

• 88887-87-0 1-methylcyclopropylamine hydrochloride 
• 194086-61-8 3,6-dichloro-4H-thieno-[3,2-e]-1,2,4-thiadiazine 1,1-dioxide 
• 319002-85-2 N-[(3-bromo-5-chlorothien-2-yl)sulfonyl]-N'-(1-methylcyclopropyl)guanidine 
• 319002-86-3 N-[(3,5-dichlorothien-2-yl)sulfonyl]-N'-(1-methylcyclopropyl)guanidine 
• 279215-55-3 6-chloro-3-fluoro-4H-thieno-[3,2-e]-1,2,4-thiadiazine 1,1-dioxide 

Relevant articles and documents

New 3-alkylamino-4H-thieno-1,2,4-thiadiazine 1,1-dioxide derivatives activate ATP-sensitive potassium channels of pancreatic beta cells

Compound 1a (NN414) is a potent opener of Kir6.2/SUR1 KATP 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-1H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1h), were found to be potent openers of Kir6.2/SUR1 KATP channels and were able to suppress glucose-stimulated insulin release from rat islets in vitro (EC50 = 0.04 ± 0.01 μM) and in vivo after intravenous or peroral administration to hyperinsulinemic obese Zucker rats (ED50 = 4.0 mg/kg). Structural modifications of this series of K ATP channel openers have provided compounds with promising pharmaco-kinetic properties indicating that brief periods of beta cell rest can be achieved.

6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives potently and selectively activate ATP sensitive potassium channels of pancreatic β-cells

6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives were synthesized and characterized as activators of adenosine 5′-triphosphate (ATP) sensitive potassium (KATP) channels in the β-cells by measuring effects on membrane potential and insulin release in vitro. The effects on vascular tissue in vitro were measured on rat aorta and small mesenteric vessels. Selected compounds were characterized as competitive inhibitors of [3H]glibenclamide binding to membranes of HEK293 cells expressing human SUR1/Kir6.2 and as potent inhibitors of insulin release in isolated rat islets. 6-Chloro-3-(1-methylcyclobutyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (54) was found to bind and activate the SUR1/Kir6.2 KATP channels in the low nanomolar range and to be at least 1000 times more potent than the reference compound diazoxide with respect to inhibition of insulin release from rat islets. Several compounds, e.g., 3-propylamino- (30), 3-isopropylamino- (34), 3-(S)-sec-butylamino- (37), and 3-(1-methylcyclopropyl)amino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (53), which were found to be potent and β-cell selective activators of KATP channels in vitro, were found to inhibit insulin secretion in rats with minimal effects on blood pressure and to exhibit good oral pharmacokinetic properties.