Synthesis and activity of tryptophan sulfonamide derivatives as novel non-hydroxamate TNF-α converting enzyme (TACE) inhibitors
A novel series of non-hydroxamate tryptophan sulfonamide derivatives containing a butynyloxy P1′ moiety was identified as inhibitors of TNF-α Converting Enzyme (TACE). The structure activity relationship of the series was examined via substitution on the tryptophan indole ring. Of the compounds inve...
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Published in | Bioorganic & medicinal chemistry Vol. 17; no. 11; pp. 3857 - 3865 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Amsterdam
Elsevier Ltd
01.06.2009
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | A novel series of non-hydroxamate tryptophan sulfonamide derivatives containing a butynyloxy P1′ moiety was identified as inhibitors of TNF-α Converting Enzyme (TACE). The structure activity relationship of the series was examined via substitution on the tryptophan indole ring. Of the compounds investigated, 2-(4-(but-2-ynyloxy)phenylsulfonamido)-3-(1-(4-methoxybenzyl)-1
H-indol-3-yl)propanoic acid (
12p) has the best in vitro potency against isolated TACE enzyme with an IC
50 of 80
nM. Compound
12p also shows good selectivity over MMP-1, -13, -14.
A novel series of non-hydroxamate tryptophan sulfonamide derivatives containing a butynyloxy P1′ moiety was identified as inhibitors of TNF-α converting enzyme (TACE). The structure–activity relationship of the series was examined via substitution on the tryptophan indole ring. Of the compounds investigated, 2-(4-(but-2-ynyloxy)phenylsulfonamido)-3-(1-(4-methoxybenzyl)-1
H-indol-3-yl)propanoic acid (
12p) has the best in vitro potency against isolated TACE enzyme with an IC
50 of 80
nM. Compound
12p also shows good selectivity over MMP-1, -13, -14. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/j.bmc.2009.04.033 |