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J Med Chem. 1992 Mar 6;35(5):800-4.

Novel inhibitors of prolyl 4-hydroxylase.

Author information

1
Chemistry 1 Department, ICI Pharmaceuticals, Macclesfield, Cheshire, United Kingdom.

Abstract

A series of 5-acyl sulfonamides derived from pyridine-2,5-dicarboxylic acid (15) has been prepared and several members of this series have been shown to be more potent, in vitro, as inhibitors of prolyl 4-hydroxylase than 15. Several chain-extended pyridinedicarboxylic acids have also been prepared and shown to be potent inhibitors of prolyl 4-hydroxylase. The structure-activity in both these series is discussed. The results indicate that the 5-carboxylic acid binding site, in the enzyme, can accept a carboxylic acid or an acyl sulfonamide equally well. This indicates a much greater degree of freedom in this distal carboxylic acid binding site than is predicted by the current theoretical model of the active site.

PMID:
1312598
DOI:
10.1021/jm00083a001
[Indexed for MEDLINE]

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