Design and synthesis of thiol containing inhibitors of matrix metalloproteinases

C A Fink; J E Carlson; C Boehm; P McTaggart; Y Qiao; J Doughty; V Ganu; R Melton; R Goldberg

doi:10.1016/s0960-894x(98)00716-1

Design and synthesis of thiol containing inhibitors of matrix metalloproteinases

Bioorg Med Chem Lett. 1999 Jan 18;9(2):195-200. doi: 10.1016/s0960-894x(98)00716-1.

Authors

C A Fink¹, J E Carlson, C Boehm, P McTaggart, Y Qiao, J Doughty, V Ganu, R Melton, R Goldberg

Affiliation

¹ Novartis Biomedical Research Institute, Summit, New Jersey 07901, USA.

PMID: 10021927
DOI: 10.1016/s0960-894x(98)00716-1

Abstract

A series of thiol containing derivatives was prepared. Several of these compounds were found to inhibit matrix metalloproteinases 1, 3, and 9 with selectivity towards 3 and 9. Compounds 15, 20, and 22 were administered to rats orally at 75 mumol/kg. Drug levels of compounds 20 and 22 in the plasma were found to exceed the IC50 values for MMP 3 and 9 four hours after administration.

MeSH terms

Animals
Dose-Response Relationship, Drug
Drug Design
Inhibitory Concentration 50
Matrix Metalloproteinase Inhibitors
Metalloendopeptidases / antagonists & inhibitors*
Rats
Sulfhydryl Compounds / administration & dosage
Sulfhydryl Compounds / blood
Sulfhydryl Compounds / chemical synthesis*
Time Factors

Substances

Matrix Metalloproteinase Inhibitors
Sulfhydryl Compounds
Metalloendopeptidases