63698-52-2

Usage

InChI:InChI=1/C9H6N2O3S/c15-9-11-10-8(14-9)5-1-2-6-7(3-5)13-4-12-6/h1-3H,4H2,(H,11,15)

Upstream product

• 6951-08-2 ethyl 1,3-benzodioxole-5-carboxylate 
• 326-56-7 methyl 3,4-methylenedioxybenzoate 
• 94-53-1 Piperonylic acid 
• 75-15-0 carbon disulfide 
• 22026-39-7 benzo[d][1,3]dioxole-5-carbohydrazide 

Downstream Products

• 63698-55-5 5-benzo[1,3]dioxol-5-yl-3H-[1,3,4]oxadiazol-2-one 
• 146942-90-7 2-(5-Benzo[1,3]dioxol-5-yl-[1,3,4]oxadiazol-2-ylsulfanyl)-1-(2,4-dichloro-phenyl)-ethanone 
• 876552-72-6 2-benzylthio-5-(3,4-methylenedioxyphenyl)-1,3,4-oxadiazole 
• 1374671-63-2 4'-((5-(benzo[d][1,3]dioxol-5-yl)-1,3,4-oxadiazol-2-ylthio)methyl)biphenyl-2-carbonitrile 
• 875456-04-5 methyl 4-(5-(benzo[d][1,3]dioxol-5-yl)-1,3,4-oxadiazol-2-ylthio)methyl benzoate 
• 876687-00-2 2-(benzo[d][1,3]dioxol-5-yl)-5-(biphenyl-4-ylmethylthio)-1,3,4-oxadiazole 
• 67572-46-7 2-((ethoxycarbonyl)methylthio)-5-(3,4-methylenedioxyphenyl)-1,3,4-oxadiazole 
• 69164-65-4 5-benzo[1,3]dioxol-5-yl-3-(2-methoxy-anilinomethyl)-3H-[1,3,4]oxadiazole-2-thione 
• 70705-14-5 5-benzo[1,3]dioxol-5-yl-3-(3-trifluoromethyl-anilinomethyl)-3H-[1,3,4]oxadiazole-2-thione 
• 69164-68-7 5-benzo[1,3]dioxol-5-yl-3-(4-chloro-anilinomethyl)-3H-[1,3,4]oxadiazole-2-thione 
• 70705-15-6 5-benzo[1,3]dioxol-5-yl-3-(diphenylamino-methyl)-3H-[1,3,4]oxadiazole-2-thione 
• 69164-61-0 3-anilinomethyl-5-benzo[1,3]dioxol-5-yl-3H-[1,3,4]oxadiazole-2-thione 
• 70705-12-3 5-benzo[1,3]dioxol-5-yl-3-(3-chloro-anilinomethyl)-3H-[1,3,4]oxadiazole-2-thione 
• 69164-62-1 5-benzo[1,3]dioxol-5-yl-3-(2-methyl-anilinomethyl)-3H-[1,3,4]oxadiazole-2-thione 

Relevant academic research and scientific papers

Synthesis, characterization and urease inhibiting derivatives of 5-(3,4-Methylenedioxyphenyl)-1,3,4-Oxadiazol-2-thiol

In the present work, the urease inhibition activity of 1,3,4-oxadiazole bearing molecules was evaluated and were found to be potential inhibitors. 3,4-(Methylenedioxy)benzoic acid (1) was employed to synthesize 5-(3,4-methylenedioxyphenyl)-1,3,4-oxadiazol-2-thiol (4) via a series of steps. It was further stepped to yield S-substituted-5-(3,4-methylenedioxyphenyl)-1,3,4-oxadiazole derivatives (6a-h) on reaction with alkyl/aralkyl halides (5a-h) in DMF using LiH as an activator. All the synthesized compounds were well supported by IR, 1H NMR and EIMS spectral analysis. The enzyme inhibition activity against urease enzyme showed these molecules as potent inhibitors of this enzyme.

Structure-based optimization of oxadiazole-based GSK-3 inhibitors

Inhibition of glycogen synthase kinase-3 (GSK-3) induces neuroprotective effects, e.g. decreases β-amyloid production and reduces tau hyperphosphorylation, which are both associated with Alzheimer's disease (AD). The two isoforms of GSK-3 in mammalians are GSK-3α and β, which share 98% homology in their catalytic domains. We investigated GSK-3 inhibitors based on 2 different scaffolds in order to elucidate the demands of the ATP-binding pocket [1]. Particularly, the oxadiazole scaffold provided potent and selective GSK-3 inhibitors. For example, the most potent inhibitor of the present series, the acetamide 26d, is characterized by an IC50 of 2 nM for GSK-3α and 17 nM for GSK-3β. In addition, the benzodioxane 8g showed up to 27-fold selectivity for GSK-3α over GSK-3β, with an IC 50 of 35 nM for GSK-3α. Two GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay to evaluate simultaneously permeability and safety.

Identification of glycogen synthase kinase-3 inhibitors with a selective sting for glycogen synthase kinase-α

The glycogen synthase kinase-3 (GSK-3) has been linked to the pathogenesis of colorectal cancer, diabetes, cardiovascular disease, acute myeloid leukemia (AML), and Alzheimer's disease (AD). The debate on the respective contributions of GSK-α and GSK-3β to AD pathology and AML is ongoing. Thus, the identification of potent GSK-α-selective inhibitors, endowed with favorable pharmacokinetic properties, may elucidate the effect of GSK-α inhibition in AD and AML models. The analysis of all available crystallized GSK-3 structures provided a simplified scheme of the relevant hot spots responsible for ligand binding and potency. This resulted in the identification of novel scorpion shaped GSK-3 inhibitors. It is noteworthy, compounds 14d and 15b showed the highest GSK-α selectivity reported so far. In addition, compound 14d did not display significant inhibition of 48 out of 50 kinases in the test panel. The GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay.

NOVEL 1,4-DIAZA-BICYCLO[3.2.1]OCTANE DERIVATIVES USEFUL AS NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS

This invention relates to novel 1,4-diaza-bicyclo[3.2.1]octane derivatives and their use in the manufacture of pharmaceutical compositions. The compounds of the invention are found to be cholinergic ligands at the nicotinic acetylcholine receptors and modulators of the monoamine receptors and transporters. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

NOVEL 1,4-DIAZA-BICYCLO[3.2.2]NONYL OXADIAZOLYL DERIVATIVES USEFUL AS MODULATOR OF NICOTINIC ACETYLCHOLINE RECEPTORS

This invention relates to novel N-oxides of a 1,4-diaza-bicyclo[3.2.2]nonyl oxadiazolyl derivative and their use in the manufacture of pharmaceutical compositions. The compounds of the invention are found to be cholinergic ligands at the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

Anticonvulsant and antiproteolytic properties of 3,5-disubstituted oxadiazole-2-thiones and their inhibition of respiration in rat brain homogenates

Eight 5-(3,4-methylenedioxyphenyl)-3-arylaminomethyl-1,3,4-oxadiazole- 2-thiones were synthesized, characterized by their sharp melting points, elemental analyses, and IR spectra, and evaluated for anticonvulsant activity. All substituted oxadiazole-2-thiones possessed anticonvulsant activity, which was reflected by their ability to provide 10-70% protection against pentylenetetrazol-induced convulsions in mice at 100 mg/kg i.p. These compounds inhibited in vitro nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, α-ketoglutarate, and NADH by rat brain homogenates as well as NAD-independent oxidation of succinate by rat brain homogenates. Antiproteolytic activity of these substituted oxadiazole-2-thiones was reflected by their ability to inhibit trypsin hydrolysis of bovine serum albumin. These results indicated that the inhibition of cellular respiration and antiproteolytic activity of these substituted oxadiazole-2-thiones is not the biochemical basis for their anticonvulsant activity.