50483-79-9

Upstream product

• 57459-16-2 (3-phenyl-[1,2,4]thiadiazol-5-yl)-ethenetricarbonitrile 
• 5852-49-3 5-phenyl-1,3,4-oxathiazol-2-one 
• 623-49-4 ethyl cyanoformate 
• 50483-82-4 3-phenyl-1,2,4-thiadiazole 
• 74466-89-0 5-Phenyl-1,2,4-thiadiazole 
• 2362-05-2 benzonitrile sulphide 
• 55-21-0 benzamide 
• 73501-00-5 5-phenyl-2-trichloromethyl-1,3,4-oxathiazole 

Downstream Products

• 138128-76-4 5-(hydroxymethyl)-3-phenyl-1,2,4-thiadiazole 
• 138129-05-2 [4-Oxo-3-(3-phenyl-[1,2,4]thiadiazol-5-ylmethyl)-3,4-dihydro-phthalazin-1-yl]-acetic acid ethyl ester 
• 138129-12-1 [4-Oxo-3-(3-phenyl-[1,2,4]thiadiazol-5-ylmethyl)-3,4-dihydro-phthalazin-1-yl]-acetic acid 
• 138128-82-2 5-(bromomethyl)-3-phenyl-1,2,4-thiadiazole 
• 50483-82-4 3-phenyl-1,2,4-thiadiazole 

Relevant academic research and scientific papers

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE

Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.

THERAPEUTICALLY ACTIVE COMPOUNDS AND THEIR METHODS OF USE

Provided are compounds useful for treating cancer and methods of treating cancer comprising administering to a subject in need thereof a compound described herein.

Microwave-induced generation and reactions of nitrile sulfides: An improved method for the synthesis of isothiazoles and 1,2,4-thiadiazoles

The 1,3-dipolar cycloaddition reactions of nitrile sulfides, generated by microwave-assisted decarboxylation of 1,3,4-oxathiazol-2-ones, have been investigated. By this approach ethyl 1,2,4-thiadiazole-5-carboxylates 3 were prepared in good yield by cycloaddition of the nitrile sulfides to ethyl cyanoformate. Similarly, reaction of benzonitrile sulfide with dimethyl acetylenedicarboxylate (DMAD) afforded dimethyl 3-phenylisothiazole-4,5- dicarboxylate (5). In contrast, o-hydroxybenzonitrile sulfide, generated from the corresponding oxathiazolone 2d, reacted with DMAD to give methyl 4-oxo-4H-[1]benzopyrano[4,3-c]isothiazole-3-carboxylate (8) in high yield. A ca. 1:1 mixture of ethyl 3-phenylisothiazole-4- and 5-carboxylates (6,7) was formed from benzonitrile sulfide and ethyl propiolate. The corresponding reaction with diethyl fumarate gave diethyl trans-4,5-dihydro-3-phenylisothiazole-4,5- dicarboylate (10). 3-Arylisothiazoles, unsubstituted at both the 4- and 5-positions, were prepared from the reaction of 5-aryl-1,3,4-oxathiazolones with norbornadiene by a pathway involving cycloaddition of the nitrile sulfide to the norbornadiene, followed by retro-Diels-Alder extrusion of cyclopentadiene from the resulting isothiazoline cycloadduct 12. In summary, the use of microwave irradiation, rather than conventional heating methods, allows nitrile sulfide generation and reactions to be carried out in shorter times, with easier work-up and, in some cases, in higher yields.

Heteroarylnitrones as drugs for neurodegenerative diseases: Synthesis, neuroprotective properties, and free radical scavenger properties

New 1,2,4-thiadiazolylnitrones and furoxanylnitrones were developed and evaluated as neuroprotective agents on a human neuroblastoma (SH-SY5Y) cells model. They inhibited at low micromolar concentrations the oxidative damage and the death induced by exposure to hydrogen peroxide. These heteroarylnitrones showed excellent peroxyl free radical absorbance capacities, analyzed by oxygen radical absorbance capacity (ORAC) assay with fluorescein as the fluorescent probe, ranging from 1.5- to 16.5-fold the value of the reference nitrone, α-phenyl-N-tert-butylnitrone (PBN). The electron spin resonance spectroscopy (ESR) demonstrated the ability of these derivatives to directly trap and stabilize oxygen, carbon, and sulfur-centered free radicals. These results demonstrated the potential use of these heteroarylnitrones as neuroprotective agents in preventing the death of cells exposed to enhanced oxidative stress and damage.

Non-ATP competitive glycogen synthase kinase 3β (GSK-3β) inhibitors: Study of structural requirements for thiadiazolidinone derivatives

The 2,4-disubstituted thiadiazolidinones (TDZD) were described as the first non-ATP competitive GSK-3β inhibitors. New modifications in this heterocyclic ring are here reported to study the influence on the biological activity. The basic skeleton of 1,2,4-thiadiazole and also one of the carbonyl groups are kept, while different modifications are introduced in positions 3 and 5, respectively. The GSK-3β activity of the new thiadiazole derivatives here synthesized showed IC50 values for some of the compounds in the micromolar range. Additionally, ATP competition studies have been carried out, showing that as well as the first generation of TDZD, these new compounds act in a non-competitive manner. With this study, additional requirements for the biological activity of the TDZD family have been delineated.

Microwave-assisted generation and reactions of nitrile sulfides

An improved practical method is described for the generation of benzonitrile sulfide based on microwave-assisted decarboxylation of 5-phenyl-1,3,4-oxathiazol-2-one. Reaction times for the preparation of cycloadducts (e.g. isothiazoles and 1,2,4-thiadiazoles) derived from the nitrile sulphide are reduced from typically 15-30 h to approximately 15 min.

Photochemistry of phenyl-substituted 1,2,4-thiadiazoles. 15N-labeling studies

Irradiation of 5-phenyl-1,2,4-thiadiazole (6) resulted in the formation of benzonitrile (5), 3-phenyl-1,2,4-thiadiazole (4), phenyl- and diphenyl-1,3,5-triazines (7 and 8), and a trace quantity of diphenyl-1,2,4-thiadiazole (9). The formation of 4, 5, 7, and 8 can be explained in terms of photoinduced electrocyclic ring closure resulting in the formation of an intermediate 4-phenyl-1,3-diaza-5-thiabicyclo[2.1.0]pentene. 15N-labeling experiments revealed that sulfur can undergo sigmatropic shifts around all four sides of the diazetine ring. Thus, irradiation of 6-4-15N led to the formation of 6-2-15N and an equimolar mixture of 4-2-15N and 4-4-15N. The thiabicyclo[2.1.0]pentene intermediate is also suggested to undergo sulfur elimination resulting in the formation of phenyldiazacyclobutadiene, which can undergo complete fragmentation to benzonitrile or [4+2] cycloaddition leading to unstable tricyclic adducts, the suggested precursors of the 1,3,5-triazine products 7 and 8. The observed 15N distribution in 7 and 8 is consistent with this mechanism. Irradiation of 4 led only to the formation of 5. 15N-labeling experiments show that 4 does not undergo electrocyclic ring closure but reacts exclusively by photofragmentation of the thiadiazole ring.

Nitrile Sulphides. Part 3. Thermal Fragmentation of 1,3,4-Oxathiazoles: Formation of Nitrile Sulphides in a Retro-1,3-dipolar Cycloaddition Reaction

On thermolysis at ca. 160 gradC 1,3,4-oxathiazoles undergo retro-1,3-dipolar cycloaddition forming nitrile sulphides and carbonyl-containing fragments.The nitrile sulphides either decompose to sulphur and nitriles or are trapped as their 1,3-dipolar cycloadducts in the presence of dipolarophiles (dimethyl acetylenedicarboxylate, ethyl cyanoformate, benzonitrile, ethyl propiolate).Similar ratios (1.32, l.34, 1.33, 1.31) of 4- and 5-ethoxycarbonyl-3-(p-methoxyphenyl)isothiazole obtained from four sources of p-methoxybenzonitrile sulphide with ethyl propriolate provide strong evidence for product formation from a discrete intermediate nitrile sulphide rather than via direct interaction of precursor with dipolarophile. 2-Dichloromethylene-1,3,4-oxathiazoles, prepared by dehydrochlorination of 2-trichloromethyloxathiazoles, prepared by dehydrochlorination of 2-trichlorometyloxathiazoles, likewise fragment to nitrile sulphides, but attempts to trap dichloroketene were unsuccessful.

Nitrile Sulphide Formation from the Thermal Fragmentation of 1,3,4-Oxathiazoles: a Retro-1,3-dipolar Cycloaddition

1,3,4-Oxathiazoles, on thermolysis, undergo retro-1,3-dipolar cycloaddition to afford carbonyl compounds and nitrile sulphides, which may be trapped by cycloaddition with alkynes and nitriles.