The synthesis and biological evaluation of non-peptidic matrix metalloproteinase inhibitors.
Novel sulfonamide matrix metalloproteinase inhibitors of general formula (9) were synthesised by a route involving a stereoselective conjugate addition reaction. Enzyme selectivity was found to be dependant on the nature of the sulfonamide substituents. Compounds (9f, 9q) are potent selective collagenase inhibitors with good oral bioavailability.
Martin
F M
FM
British Biotech Pharmaceuticals Limited, Cowley, Oxford. martinf@britbio.co.uk
Beckett
R P
RP
Bellamy
C L
CL
Courtney
P F
PF
Davies
S J
SJ
Drummond
A H
AH
Dodd
R
R
Pratt
L M
LM
Patel
S R
SR
Ricketts
M L
ML
Todd
R S
RS
Tuffnell
A R
AR
Ward
J W
JW
Whittaker
M
M
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001682:Biological Availability; D006860:Hydrogen Bonding; D006877:Hydroxamic Acids / Q000737:chemistry / Q000494:pharmacology; D061965:Matrix Metalloproteinase Inhibitors; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D013449:Sulfonamides; C100342:marimastat