5577-42-4

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A methanesulfonamide analogue of Rofecoxib as COX inhibitors.

InChI:InChI=1/C12H16N2O2/c1-10-4-2-3-5-11(10)13-12(15)14-6-8-16-9-7-14/h2-5H,6-9H2,1H3,(H,13,15)

Upstream product

• 5317-89-5 4'-(methylsulfonylamino)acetophenone 
• 99-92-3 p-aminobenzophenone 
• 367-27-1 2,4-difluorophenol 
• 1197-22-4 N-phenylmethanesulfonamide 
• 598-21-0 2-Bromoacetyl bromide 

Downstream Products

• 129280-15-5 4'-(2-dibenzylaminoacetyl)methanesulfonanilide 
• 919122-30-8 4-methylsulfonamidophenacyl phenylacetate 
• 104691-52-3 2-(4-Methylsulphonamido-phenyl)-imidazo[1,2-a]pyrimidine 
• 113049-43-7 N-{4-[2-(4-[4-Nitro-2-pyridinyl]-1-piperazinyl)acetyl]phenyl}methanesulphonamide 
• 113049-58-4 N-{4-[(4-acetyl-1-piperazinyl)acetyl]phenyl}methanesulphonamide 
• 476338-85-9 N-(4-(2-aminothiazol-4-yl)phenyl)methanesulfonamide 

Relevant academic research and scientific papers

Discovery and structure-activity relationship of novel 4-hydroxy-thiazolidine-2-thione derivatives as tumor cell specific pyruvate kinase M2 activators

Pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter aberrant metabolism in cancer cells. In this study, we discovered a 4-hydroxy-thiazolidine-2-thione compound 2 as a novel PKM2 activator from a random screening of an in-house compound library. Then a series of novel 4-hydroxy-thiazolidine-2-thione derivatives were designed and synthesized for screening as potent PKM2 activators. Among these, some compounds showed higher PKM2 activation activity than lead compound 2 and also exhibited significant anti-proliferative activities on human cancer cell lines at nanomolar concentration. The compound 5w was identified as the most potent antitumor agent, which showed excellent anti-proliferative effects with IC50 values from 0.46 μM to 0.81 μM against H1299, HCT116, Hela and PC3 cell lines. 5w also showed less cytotoxicity in non-tumor cell line HELF compared with cancer cells. In addition, Preliminary pharmacological studies revealed that 5w arrests the cell cycle at the G2/M phase in HCT116 cell line. The best PKM2 activation by compound 5t was rationalized through docking studies.

Design, synthesis and structure-activity relationship studies of novel and diverse cyclooxygenase-2 inhibitors as anti-inflammatory drugs

Because of the pivotal role of cyclooxygenase (COX) in the inflammatory processes, non-steroidal anti-inflammatory drugs (NSAIDs) that suppress COX activities have been used clinically for the treatment of inflammatory diseases/syndromes; however, traditional NSAIDs exhibit serious side-effects such as gastrointestinal damage and hyper sensitivity owing to their COX-1 inhibition. Also, COX-2 inhibition-derived suppressive or preventive effects against initiation/proliferation/invasion/motility/recurrence/metastasis of various cancers/tumours such as colon, gastric, skin, lung, liver, pancreas, breast, prostate, cervical and ovarian cancers are significant. In this study, design, synthesis and structure-activity relationship (SAR) of various novel {2-[(2-, 3- and/or 4-substituted)-benzoyl, (bicyclic heterocycloalkanophenyl)carbonyl or cycloalkanecarbonyl]-(5- or 6-substituted)-1H-indol-3-yl}acetic acid analogues were investigated to seek and identify various chemotypes of potent and selective COX-2 inhibitors for the treatment of inflammatory diseases, resulting in the discovery of orally potent agents in the peripheral-inflammation model rats. The SARs and physicochemical properties for the analogues are described as significant findings. For graphical abstract: see Supplementary Material. (www.informahealthcare.com/enz)

Asymmetric reduction of N-[4-(2-bromoacetyl)phenyl]methanesulfonamide by employing Candida viswanathii MTCC 5158

Enantioselective synthesis of chiral drugs by chemoenzymatic processes have attracted attention in which the crucial stereogenic step involves an enzymatic reaction by virtue of chemo-, regio- and enantio- selectivity and eco-friendly nature of biocatalysis, (S)-sotalol a β-blocker, belongs to class-III antiarrhythmic agents. To avoid the side effects of racemic sotalol, efforts have been put forward to synthesize a key intermediate for the synthesis of (S)-enantiomer of sotalol, which is more potent than the (R)-enantiomer. The aryl ketone, N-(4-acetyl-phenyl) methanesulfonamide was synthesized from the initial substrate 4-aminoacetophenone. Further, the bromination of aryl ketone was carried out to obtain N-[4-(2-bromo-acetyl)-phenyl]-methanesulfonamide. The chemical reduction as well as biological reduction of aryl ketone was carried out to obtain a racemate alcohol N [4-(2-bromo-1-hydroxy-ethyl) (4-methanesulfonamide)]ethanol and chiral (S)-N-[4-(2-bromo-1-hydroxy-ethyl)(4- methanesulfonamide)]ethanol, respectively. (S)-N-[-4-(2-bromo-1-hydroxy-ethyl) (4- methanesulfonamide)]ethanol is a key intermediate for the synthesis of (S)-sotalol. The biological reduction was carried out by using whole cells and found that 96 % conversion was obtained at 12th h of reaction after that the percentage conversion decreased.

Synthesis and biological evaluation of methanesulfonamide analogues of rofecoxib: Replacement of methanesulfonyl by methanesulfonamido decreases cyclooxygenase-2 selectivity

A new group of 3-(4-substituted-phenyl)-4-(4-methylsulfonamidophenyl)-2(5H)furanones in which the methylsulfonyl (MeSO2) COX-2 pharmacophore present in rofecoxib was replaced by a methanesulfonamido (MeSO2NH) moiety, and where the substituent at the para-position of the C-3 phenyl ring was simultaneously varied (H, F, Cl, Br, Me, OMe), were evaluated to determine the combined effects of steric and electronic substituent properties upon COX-1 and COX-2 inhibitory potency and COX isozyme selectivity. Structure-activity relationship (SAR) studies showed that compounds having a neutral (H), or electronegative halogen (F, Cl, Br), substituent at the para-position of the C-3 phenyl ring inhibited both COX-1 and COX-2 with COX-2 selectivity indexes in the 3.1-39.4 range. In contrast, compounds having an electron-donating Me or OMe substituent were selective inhibitors of COX-2 (COX-1 IC50 > 100 μM). These SAR data indicate the 3-aryl-4-(4-methylsulfonamidophenyl)-2(5H)furanone scaffold provides a suitable template to design COX inhibitors with variable COX-2 selectivity indexes.

Pyrrole derivatives and medicinal composition

The invention relates to a pharmaceutical composition comprising a pyrrole derivative of the following formula [1] or a pharmaceutically acceptable salt thereof, or a solvate of either of them, as an active ingredient. STR1 (wherein R1 represents hydrogen or alkoxycar91 bonylamino, R2 represents alkyl, aryl which may be substituted, aromatic heterocyclyl which may be substituted, unsubstituted amino, monoalkylamino, dialkylamino, or cyclic amino which may be substituted; R3 represents cyano or carbamoyl; R4 represents hydrogen or alkyl; E represents alkylene; q is equal to 0 or 1, A represents methyl, aryl which may be substituted, or aromatic heterocyclyl which may be substituted). The pharmaceutical composition of the invention is effective for the treatment of pollakiuria or urinary incontinence.

Process development of a novel anti-inflammatory agent. The regiospecific bromination of 4′-acetylmethanesulfonanilide

An efficient, practical synthesis of a novel antiinflammatory agent (FK3311, 1) which is acceptable environmentally and could be used for pilot plant manufacture is described. Regiospecific bromination of 4′-acetylmethanesulfonanilide, allowing selective side chain or nuclear halogenation, also has been investigated. Development efforts focused on the optimized Ullmann coupling reaction conditions and the isolation and purification of 1 to give satisfactory quality product (99.8% purity) according to the new and concise synthetic route.

Antiarrhythmic N-aminoalkylene alkyl and aryl sulfonamides

The present invention provides novel sulfonanilide and benzene-alkylaminium compounds which are the products of processes utilizing novel intermediates. Both the novel compounds and the novel intermediates are useful for the therapeutic or prophylactic treatment of arrhythmic activity.

Adrenergic sulfonanilides. 4. Centrally active beta-adrenergic agonists.

The central nervous system (CNS) activities of a number of soterenol analogs have been investigated, and several of these compounds possessed potent morphine antagonistic and anorexiant properties. The CNS activity of these compounds was enhanced by certain lipophilic [e.g., 1,1-dimethyl-2-phenethyl (43) or cyclopropyl (40 and 44)] nitrogen substituents; however, minor structural changes on either the aromatic or side-chain moieties drastically reduced central activity. Toxicity in this series was related to the inherent alpha-adrenergic stimulating component (direct or indirect).