145337-55-9

Upstream product

• 145337-57-1 (R)-3-((S)-2,2-Dimethyl-1-methylcarbamoyl-propylcarbamoyl)-5-methyl-hexanoic acid 
• 37755-48-9 benzyl (R)-2-hydroxy-4-methylpentanoate 
• 927828-06-6 (S)-N₄-(benzyloxy)-N₁-((S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-2-isobutylsuccinamide 
• 200866-11-1 (R)-methyl 3-((S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-5-methylhexanoate 
• 145337-54-8 (R)-N⁴-Benzyloxy-N¹-((S)-2,2-dimethyl-1-methylcarbamoyl-propyl)-2-isobutyl-succinamide 
• 184948-24-1 tert-butyl (2R)-1,2-dibenzyl 4-methylpentane-1,1,2-tricarboxylate 
• 145337-56-0 (R)-3-((S)-2,2-Dimethyl-1-methylcarbamoyl-propylcarbamoyl)-5-methyl-hexanoic acid tert-butyl ester 
• 219616-31-6 2-(tert-butoxycarbonyl)-(3R)-3-isobutylsuccinic acid 
• 112245-04-2 (R)-2-(2-(tert-butoxy)-2-oxoethyl)-4-methylpentanoic acid 
• 130317-28-1 benzyl 2R-trifluoromethanesulfonyloxy-4-methylvalerate 
• 20312-37-2 (R)-2-hydroxy-4-methylpentanoic acid 
• 171347-91-4 (R)-5-Methyl-3-((S)-1-phenyl-ethylcarbamoyl)-hexanoic acid methyl ester 
• 162678-79-7 (2R)-2-[(methoxycarbonyl)methyl]-4-methylpentanoic acid 
• 200865-04-9 (S)-(2,2-dimethyl-1-methylcarbamoylpropyl)carbamic acid tert-butyl ester 

Relevant academic research and scientific papers

Novel method of treatment of inflammatory skin conditions

There is provided, inter alia, a method for the treatment or prevention of an inflammatory skin condition which is characterised by colonisation with Staphylococcus aureus, comprising the topical administration of an aureolysin inhibitor.

USE OF AN AUREOLYSIN INHIBITOR FOR THE TREATMENT OF INFLAMMATORY SKIN CONDITIONS CHARACTERISED BY COLONISATION WITH STAPHYLOCOCCUS AUREUS

There is provided, inter alia, a method for the treatment or prevention of an inflammatory skin condition which is characterised by colonisation with Staphylococcus aureus, comprising the topical administration of an aureolysin inhibitor.

Solid-phase synthesis of hydroxamic acid based TNF-α convertase inhibitors

An acid-sensitive linker for the solid phase synthesis of hydroxamic acids is described. Hydroxamic acid based TNFα inhibitors have been prepared by solid phase synthesis: derivatisation of N2-[4-(N-oxyamino)-2R-isobutyl- 3S-aminosuecinyl]-L-te

New hydroxylamines for the synthesis of hydroxamic acids

O-2,4-Dimethoxybenzyl hydroxylamine and O-2,4-dimethoxybenzyl-N-2,4,6- trimethoxybenzyl hydroxylamine have been prepared and used for the preparation of hydroxamic acid based inhibitors of biological interest.

Inhibition of membrane-type 1 matrix metalloproteinase by hydroxamate inhibitors: An examination of the subsite pocket

The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of pro-gelatinase A (proMMP-2), which is associated with tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play an important role in pathophysiological digestion of ECM. We studied the inhibitory effect of various hydroxamate MMP inhibitors, including known inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of MT1-MMP lacking the transmembrane domain (ΔMT1) to further characterize the enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the inhibitory activities of various hydroxamates reveals general structural profiles affecting selectivities toward MMPs. In particular, a longer side chain at the P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For the P2' position, an α-branched alkyl group is critical for the binding toward ΔMT1, while the introduction of a bulky group at the α-position of hydroxamic acid seems to diminish the activity against ΔMT1. Summation of the data on the sensitivity of ΔMT1 to various hydroxamate inhibitors indicates that (1) the volume of the S1' subsite of ΔMT1 is similar to that of MMP-2, -3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites are narrower than those in other MMPs. On the basis of these results, the hydroxamates with a P1' phenylpropyl and P2' α-branched alkyl group were synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed strong activity against ΔMT1 over MMP-1, but no selectivity between ΔMT1 and MMP-9. These results are explained using molecular modeling studies conducted on MT1-MMP.

Matrix metalloproteinase inhibitors: A structure-activity study

Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids inaddition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (2) Potent inhibitorsmust possess string zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustratedby itsability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.

Design and synthesis of the cartilage protective agent (CPA, Ro32-3555)

A novel series of MMP inhibitors has been identified. The compounds are potent selective inhibitors of collagenase with good solubility and oral bioavailability. One compound, designated Ro32-3555, has been selected for development as a cartilage protective agent for use in the treatment of rheumatoid- and osteoarthritis.