779341-90-1

Upstream product

• 13518-40-6 t-butyl D-valinate hydrochloride 
• 98-58-8 4-bromobenzenesulfonyl chloride 
• 817164-43-5 (R)-2-(4-bromophenylsulfonamido)-3-methylbutanoic acid 
• 36805-97-7 N,N-dimethylformamide di-tert-butyl acetal 
• 640-68-6 D-Val-OH 
• 2528-15-6 D-valine t-butyl ester 

Downstream Products

• 854371-72-5 (R)-2-[4'-(benzothiazol-2-yloxymethyl)-biphenyl-4-sulfonylamino]-3-methyl-butyric acid tert-butyl ester 
• 871574-46-8 tert-butyl N-[(4'-{[(1-benzofuran-2-ylcarbonyl)amino]methyl}-1,1'-biphenyl-4-yl)sulfonyl]-D-valinate 
• 871574-47-9 tert-butyl N-[(4'-{[(1-benzofuran-2-ylcarbonyl)oxy]methyl}-1,1'-biphenyl-4-yl)sulfonyl]-D-valinate 
• 854372-23-9 tert-butyl N-[(4'-{[(3-methyl-1-benzofuran-2-yl)carbonyl]oxy}-1,1'-biphenyl-4-yl)sulfonyl]-D-valinate 
• 871574-44-6 tert-butyl N-({4'-[(1-benzofuran-2-ylsulfonyl)oxy]-1,1'-biphenyl-4-yl}sulfonyl)-D-valinate 
• 854372-24-0 benzofuran-2-carboxylic acid 4'-(1-tert-butoxycarbonyl-2-methylpropylsulfamoyl)biphenyl-4-yl ester 
• 854371-76-9 D-2-[4'-(benzofuran-2-ylmethoxy)biphenyl-4-sulfonylamino]-3-methylbutyric acid tert-butyl ester 

Relevant academic research and scientific papers

Sugar-Based Arylsulfonamide Carboxylates as Selective and Water-Soluble Matrix Metalloproteinase-12 Inhibitors

Matrix metalloproteinase-12 (MMP-12) can be considered an attractive target to study selective inhibitors useful in the development of new therapies for lung and cardiovascular diseases. In this study, a new series of arylsulfonamide carboxylates, with increased hydrophilicity resulting from conjugation with a β-N-acetyl-d-glucosamine moiety, were designed and synthesized as MMP-12 selective inhibitors. Their inhibitory activity was evaluated on human MMPs by using the fluorimetric assay, and a crystallographic analysis was performed to characterize their binding mode. Among these glycoconjugates, a nanomolar MMP-12 inhibitor with improved water solubility, compound 3 [(R)-2-(N-(2-(3-(2-acetamido-2-deoxy-β-d-glucopyranosyl)thioureido)ethyl)biphenyl-4-ylsulfonamido)-3-methylbutanoic acid], was identified.

Synthesis and biological evaluation of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides: A class of potent aggrecanase-1 inhibitors

The prevention of aggrecan (a key component of cartilage) cleavage via the inhibition of aggrecanase-1 may provide a unique opportunity to stop the progression of cartilage degradation in osteoarthritis. The evaluation of a series of biphenylsulfonamides

Synthesis and biological evaluation of biphenylsulfonamide carboxylate aggrecanase-1 inhibitors

Aggrecanases are recently discovered enzymes that cleave aggrecan, a key component of cartilage. Aggrecanase inhibitors may provide a unique means to halt the progression of cartilage destruction in osteoarthritis. The synthesis and evaluation of biphenyl

Biaryl sulfonamides and methods for using same

The present invention relates to biaryl sulfonamides and their use as, for example, metalloproteinase inhibitors.

Biaryl sulfonamides and methods for using same

The present invention relates to biaryl sulfonamides and their use as, for example, metalloproteinase inhibitors.

Structure-activity relationships and pharmacokinetic analysis for a series of potent, systemically available biphenylsulfonamide matrix metalloproteinase inhibitors

A series of biphenylsulfonamide derivatives of (S)-2-(biphenyl-4- sulfonylamino)-3-methylbutyric acid (5) were prepared and evaluated for their ability to inhibit matrix metalloproteinases (MMPs). For this series of compounds, our objective was to systematically replace substituents appended to the biphenyl and α-position of 5 with structurally diverse functionalities to assess the effects these changes have on biological and pharmacokinetic activity. The ensuing structure-activity relationship (SAR) studies showed that biphenylsulfonamides substituted with bromine in the 4'- position (11c) significantly improved in vitro activity and exhibited superior pharmacokinetics (C(max), t(1/2), AUCs), relative to compound 5. Varying the lipophilicity of the α-position by replacing the isopropyl group of 11c with a variety of substituents, in general, maintained potency versus MMP-2, -3, and -13 but decreased the oral systemic availability. Subsequent evaluation of its enantiomer, 11c', showed that both compounds were equally effective MMP inhibitors. In contrast, the corresponding hydroxamic acid enantiomeric pair, 16a (S-isomer) and 16a' (R-isomer), stereoselectivity inhibited MMPs. For the first time in this series, 16a' provided nanomolar potency against MMP-1, -7, and -9 (IC50'S = 110, 140, and 18 nM, respectively), whereas 16a was less potent against these MMPs (IC(50)'S = 24, 78, and 84 μM, respectively). However, unlike 11c, compound 16a' afforded very low plasma concentrations following a single 5 mg/kg oral dose in rat. Subsequent X-ray crystal structures of the catalytic domain of stromelysin (MMP-3CD) complexed with inhibitors from closely related series established the differences in the binding mode of carboxylic acid-based inhibitors (11c,c') relative to the corresponding hydroxamic acids (16a,a').