75744-85-3

Upstream product

• 1121-24-0 ortho-mercaptophenol 
• 2388-73-0 1-methoxy-2-(methylsulfanyl)benzene 
• 108-24-7 acetic anhydride 
• 1073-29-6 2-(methylsulfenyl)phenol 

Relevant academic research and scientific papers

Covalent modification of cyclooxygenase-2 (COX-2) by 2-acetoxyphenyl alkyl sulfides, a new class of selective COX-2 inactivators

All of the selective COX-2 inhibitors described to date inhibit the isoform by binding tightly but noncovalently at the substrate binding site. Recently, we reported the first account of selective covalent modification of COX-2 by a novel inactivator, 2-acetoxyphenyl hept-2-ynyl sulfide (70) (Science 1998, 280, 1268-1270). Compound 70 selectively inactivates COX-2 by acetylating the same serine residue that aspirin acetylates. This paper describes the extensive structure-activity relationship (SAR) studies on the initial lead compound 2-acetoxyphenyl methyl sulfide (36) that led to the discovery of 70. Extension of the S-alkyl chain in 36 with higher alkyl homologues led to significant increases in inhibitory potency. The heptyl chain in 2-acetoxyphenyl heptyl sulfide (46) was optimum for COX-2 inhibitory potency, and introduction of a triple bond in the heptyl chain (compound 70) led to further increments in potency and selectivity. The alkynyl analogues were more potent and selective COX-2 inhibitors than the corresponding alkyl homologues. Sulfides were more potent and selective COX-2 inhibitors than the corresponding sulfoxides or sulfones or other heteroatom-containing compounds. In addition to inhibiting purified COX-2, 36, 46, and 70 also inhibited COX-2 activity in murine macrophages. Analogue 36 which displayed moderate potency and selectivity against purified human COX-2 was a potent inhibitor of COX-2 activity in the mouse macrophages. Tryptic digestion and peptide mapping of COX-2 reacted with [1-14C-acetyl]-36 indicated that selective COX-2 inhibition by 36 also resulted in the acetylation of Ser516. That COX-2 inhibition by aspirin resulted from the acetylation of Ser516 was confirmed by tryptic digestion and peptide mapping of COX-2 labeled with [1- 14C-acetyl]salicyclic acid. The efficacy of the sulfides in inhibiting COX- 2 activity in inflammatory cells, our recent results on the selectivity of 70 in attenuating growth of COX-2-expressing colon cancer cells, and its selectivity for inhibition of COX-2 over COX-1 in vivo indicate that this novel class of covalent modifiers may serve as potential therapeutic agents in inflammatory and proliferative disorders.

Studies on the Synthesis of Heterocyclic Compounds. XIV. Cleavage of 1,3-Benzoxathioles by Magnesium Bromide-Acetic Anhydride

The cleavage reaction of some 1,3-benzoxathioles with magnesium bromide and acetic anhydride has been studied.In all the 1,3-benzoxathioles studied, the opening of the heterocyclic ring occurs first with cleavage of the C-O bond and formation of bromides and their corresponding products of hydrolysis.Successively also the cleavage of the C-S bond can occur.The competitive electrophilic substitution on the benzene ring becomes appreciable only in the 1,3-benzoxathioles-2,2-disubstituted with sterically demanding groups.The structure of newly prepared compounds has been determined by analytical and spectroscopic data and when possible by comparison with authentic samples.

Acyl transfer in o-hydroxybenzenethiol

o-Hydroxybenzenethiol reacts with one equivalent of acetic anhydride to give a mixture of starting material, diacetylated material, and O- or S-monoacetylated products as determined by nmr.The same products are obtained by equilibration of a mixture of o-