1997
DOI: 10.1016/s0960-894x(97)00125-x
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A novel series of matrix metalloproteinase inhibitors for the treatment of inflammatory disorders

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Cited by 39 publications
(44 citation statements)
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“…MMPIs that utilize thiol ZBGs have been synthesized and demonstrate, in some cases, inhibition at sub-nanomolar concentrations [109][110][111][112][113]. Thiol-based MMPIs have been of interest due to the apparent thiophilicity of the zinc (II) ion in a number of proteins.…”
Section: Thiol-based Mmpismentioning
confidence: 99%
“…MMPIs that utilize thiol ZBGs have been synthesized and demonstrate, in some cases, inhibition at sub-nanomolar concentrations [109][110][111][112][113]. Thiol-based MMPIs have been of interest due to the apparent thiophilicity of the zinc (II) ion in a number of proteins.…”
Section: Thiol-based Mmpismentioning
confidence: 99%
“…A recent publication discloses, for the first time, the biological activity of these compounds. The prototypic compound 1 is a modestly active, broad spectrum inhibitor that is reported to be orally active at 40 mpk in an adjuvant rat model of rheumatoid arthritis [9]. A patent application describing close analogues of compound 1 was published early in 1996, and this patent has already been analysed in this journal [10].…”
Section: Resultsmentioning
confidence: 99%
“…The absence of a strong Zn chelator makes it very unlikely that these compounds will exhibit significant inhibition of MMPs or TNF release. The propionoyl compound 9 has been reported to be inactive in MMP-3, 8 and 9 inhibition assays, 'demonstrating that the thiol group is essential for activity' [9]. The two other patents describe compounds with less drastic changes.…”
Section: Resultsmentioning
confidence: 99%
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“…For example, the hydroxyl group of these inhibitors is rapidly glucuronidated and may also be reduced and ultimately metabolized to a free acid (Hodgson 1995). Consequently, a number of groups, including ourselves, have attempted to utilize other chelating groups such as the carboxylates (Chapman et al 1993) and thiols (Celltech-Chiroscience) (Baxter et al 1997 ;Lynas et al 2000).…”
Section: Mmp Family Examples Actionsmentioning
confidence: 99%