An unexpected synthesis of 3,5-diaryl-1,2,4-thiadiazoles from thiobenzamides and methyl bromocyanoacetate

Mayhoub, Abdelrahman S.; Kiselev, Evgeny; Cushman, Mark

doi:10.1016/j.tetlet.2011.07.068

Cited by 26 publications

(9 citation statements)

References 18 publications

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“…Although there are numerous methods reported for synthesis of 3,5-disubstituted-1,2,4-thiadiazoles with identical substituents, 46–51 there are a limited number for preparation of those with non-identical substituents. 52 In the present case, Howe’s method 52 was followed, and oxathiazolones 5a , b , prepared from benzamides 4a , b and (chlorocarbonyl)sulfenyl chloride, were allowed to react with benzonitrile and its o -fluoro derivative in heated decaline to afford compounds 6a and 6b in low yields, respectively (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

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Optimization of thiazole analogues of resveratrol for induction of NAD(P)H:quinone reductase 1 (QR1)

Mayhoub

Marler

Kondratyuk

et al. 2012

Bioorganic & Medicinal Chemistry

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NAD(P)H:quinone reductase 1 (QR1) belongs to a class of enzymes called cytoprotective enzymes. It exhibits its cancer protective activity mainly by inhibiting the formation of intracellular semiquinone radicals, and by generating α-tocopherolhydroquinone, which acts as a free radical scavenger. It is therefore believed that QR1 inducers can act as cancer chemopreventive agents. Resveratrol (1) is a naturally occurring stilbene derivative that requires a concentration of 21 μM to double QR1 activity (CD = 21 μM). The stilbene double bond of resveratrol was replaced with a thiadiazole ring and the phenols were eliminated to provide a more potent and selective derivative 2 (CD = 2.1 μM). Optimizing the substitution pattern of the two phenyl rings and the central heterocyclic linker led to a highly potent and selective QR1 inducer 9o with a CD value of 0.087 μM.

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Section: Resultsmentioning

confidence: 99%

“…HPLC analyses were performed on a Waters binary HPLC system (Model 1525, 20 μL injection loop) equipped with a Waters dual wavelength absorbance UV detector (Model 2487) set for 254 nm, and using a 5 μm C-18 reverse phase column. Compounds 15 , 55 16 46 and 14a–f 45 were prepared as reported.…”

Section: Methodsmentioning

confidence: 99%

Optimization of thiazole analogues of resveratrol for induction of NAD(P)H:quinone reductase 1 (QR1)

Mayhoub

Marler

Kondratyuk

et al. 2012

Bioorganic & Medicinal Chemistry

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“…Synthesis of 3,5‐diaryl‐1,2,4‐thiadiazoles by condensation of aryl thioamides with methyl 2‐bromo‐2‐cyanoacetate …”

Section: Formation and Functionalization Of The 124‐thiadiazole mentioning

confidence: 99%

“…Amazingly, at almost the same time, Cushman and co-workers reported a very similar procedure with a series of benzothioamides 59 and methyl 2-bromo-2-cyanoacetate (60; Scheme 24), providing quantitative yields of 3,5-diaryl-1,2,4thiadiazoles 61 with an easy workup and a high degree of product purity. [45] Scheme 24. Synthesis of 3,5-diaryl-1,2,4-thiadiazoles by condensation of aryl thioamides with methyl 2-bromo-2-cyanoacetate.…”

Section: Synthesis Of 124-thiadiazoles Through Condensation Reactionsmentioning

confidence: 99%

Building 1,2,4‐Thiadiazole: Ten Years of Progress

2017

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Thiadiazoles are among the privileged pharmacological building blocks due to their unique chemical properties for diverse biological and clinical applications. 1,2,4‐Thiadiazole derivatives have recently attained a therapeutic and economic importance that they did not possess a few years ago, thus leading to growing interest in this class of heterocycles. Moreover, the importance of such molecules is not restricted to medicinal chemistry; they also perform well as N,S ligands in coordination chemistry or as important intermediates for fine‐chemicals synthesis. In this context, this review systematizes the main advances in the synthesis of 1,2,4‐thiadiazole‐based compounds in the last ten years and discloses some relevant applications of these compounds during that period.

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“…The replacement of the stilbene ethylene linker with different heterocycles is a common strategy in medicinal chemistry used to improve the pharmacokinetics and/or pharmacodynamics of stilbenes (Scheme 5) [44–46]. In the case of Aβ probes, a series of 2,5-diphenyl-1,3,4-oxadiazoles 50a – f and 3,5-diphenyl-1,2,4-oxadiazoles 51a – e have been studied in this respect (Table 3 and Table 4).…”

Section: Reviewmentioning

confidence: 99%

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

Eckroat¹,

Mayhoub²

2013

Beilstein J. Org. Chem.

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SummaryThe number of people suffering from Alzheimer’s disease (AD) is expected to increase dramatically in the coming years, placing a huge burden on society. Current treatments for AD leave much to be desired, and numerous research efforts around the globe are focused on developing improved therapeutics. In addition, current diagnostic tools for AD rely largely on subjective cognitive assessment rather than on identification of pathophysiological changes associated with disease onset and progression. These facts have led to numerous efforts to develop chemical probes to detect pathophysiological hallmarks of AD, such as amyloid-β plaques, for diagnosis and monitoring of therapeutic efficacy. This review provides a survey of chemical probes developed to date for AD with emphasis on synthetic methodologies and structure–activity relationships with regards to affinity for target and brain kinetics. Several probes discussed herein show particularly promising results and will be of immense value moving forward in the fight against AD.

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An unexpected synthesis of 3,5-diaryl-1,2,4-thiadiazoles from thiobenzamides and methyl bromocyanoacetate

Abstract: Aryl thioamides undergo a very rapid condensation in the presence of methyl bromocyanoacetate to provide quantitative yields of 3,5-diaryl-1,2,4-thiadiazoles with easy work-up and a high degree of product purity. The method can be scaled up with no loss in efficiency.

Cited by 26 publications

References 18 publications

Optimization of thiazole analogues of resveratrol for induction of NAD(P)H:quinone reductase 1 (QR1)

Optimization of thiazole analogues of resveratrol for induction of NAD(P)H:quinone reductase 1 (QR1)

Building 1,2,4‐Thiadiazole: Ten Years of Progress

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

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