Publications by authors named "David How"

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 resulted in the identification of the ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides analogs (19-21 and 24) with improved Agg-1 inhibition and MMP-2, MMP-13 activity.

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Deprotection of p-nitrobenzyl esters and valyl carbamates in carbapenem CL 192,276 produced the active compound OCA-983 in excellent yields. Straight chain alkanols such as 1-butanol, 1-pentanol and 1-hexanol in water at certain ratios were effective solvent systems. Alkyl acetates in water also resulted in simultaneous deprotection of PNB and PNZ side-chains albeit at slower rates.

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The effect of introducing hydrophobic groups onto the disaccharide portion of the mannopeptimycins has been examined. Under acid-catalyzed conditions dimethyl acetals and ketals react on the terminal mannose of the disaccharide moiety of mannopeptimycin-alpha and the cyclohexylalanyl analogue 2. The preferentially formed monofunctionalized 4,6-acetals and -ketals display potent antibacterial activities against Gram-positive microorganisms, including MRSA, PRSP, and VRE pathogens.

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A number of 6-O-ether and 4-O-ether derivatives of mannopeptimycin-alpha with different steric bulk and lipophilicity were synthesized for structure-activity relationship study. Novel iodo and bromo mannopeptimycin-alpha were also prepared. These compounds were synthesized via electrophilic aromatic substitution.

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A series of benzoxazole derivatives of the mannopeptimycin glycopeptide antibiotics was synthesized via a novel benzoxazole formation reaction by treating aminophenol of mannopeptimycin-beta with an aldehyde and DDQ in DMF. Some of these derivatives (e.g.

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Novel ether derivatives of mannopeptimycin glycopeptide were synthesized to probe their SAR. Many of these derivatives exhibited potent antibacterial activity against methicillin resistant and vancomycin resistant strains. These ether derivatives were prepared via reductive ring cleavage of acetals to give a mixture of 6-O, 4-O, 3-O, and 2-O-ether isomers.

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