461437-53-6

Basic information

• Product Name: 2-[(1,1-dioxido-1-benzothien-3-yl)sulfanyl]-5-(4-methylphenyl)-1,3,4-oxadiazole
• Synonyms: 2-[(1,1-dioxido-1-benzothien-3-yl)sulfanyl]-5-(4-methylphenyl)-1,3,4-oxadiazole
• CAS NO: 461437-53-6
• Molecular Formula: C17H12N2O3S2
• Molecular Weight: 356.41878
• Mol File: 461437-53-6.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• CAS DataBase Reference: 2-[(1,1-dioxido-1-benzothien-3-yl)sulfanyl]-5-(4-methylphenyl)-1,3,4-oxadiazole(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[(1,1-dioxido-1-benzothien-3-yl)sulfanyl]-5-(4-methylphenyl)-1,3,4-oxadiazole(461437-53-6)
• EPA Substance Registry System: 2-[(1,1-dioxido-1-benzothien-3-yl)sulfanyl]-5-(4-methylphenyl)-1,3,4-oxadiazole(461437-53-6)

Safety Data

• Hazardous Substances Data: 461437-53-6(Hazardous Substances Data)

Upstream product

• 16957-97-4 3-bromobenzothiophene S,S-dioxide 
• 31130-15-1 2-mercapto-5-(4-methylphenyl)-1,3,4-oxadiazole 
• 7342-82-7 3-Bromothianaphthene 

Relevant articles and documents

Antifungal benzo[b]thiophene 1,1-dioxide IMPDH inhibitors exhibit pan-assay interference (PAINS) profiles

Fungi cause serious life-threatening infections in immunocompromised individuals and current treatments are now complicated by toxicity issues and the emergence of drug resistant strains. Consequently, there is a need for development of new antifungal drugs. Inosine monophosphate dehydrogenase (IMPDH), a key component of the de novo purine biosynthetic pathway, is essential for growth and virulence of fungi and is a potential drug target. In this study, a high-throughput screen of 114,000 drug-like compounds against Cryptococcus neoformans IMPDH was performed. We identified three 3-((5-substituted)-1,3,4-oxadiazol-2-yl)thio benzo[b]thiophene 1,1-dioxides that inhibited Cryptococcus IMPDH and also possessed whole cell antifungal activity. Analogs were synthesized to explore the SAR of these hits. Modification of the fifth substituent on the 1,3,4-oxadiazole ring yielded compounds with nanomolar in vitro activity, but with associated cytotoxicity. In contrast, two analogs generated by substituting the 1,3,4-oxadiazole ring with imidazole and 1,2,4-triazole gave reduced IMPDH inhibition in vitro, but were not cytotoxic. During enzyme kinetic studies in the presence of DTT, nucleophilic attack of a free thiol occurred with the benzo[b]thiophene 1,1-dioxide. Two representative compounds with substitution at the 5 position of the 1,3,4-oxadiazole ring, showed mixed inhibition in the absence of DTT. Incubation of these compounds with Cryptococcus IMPDH followed by mass spectrometry analysis showed non-specific and covalent binding with IMPDH at multiple cysteine residues. These results support recent reports that the benzo[b]thiophene 1,1-dioxides moiety as PAINS (pan-assay interference compounds) contributor.