Selectivity of inhibition of matrix metalloproteases MMP-3 and MMP-2 by succinyl hydroxamates and their carboxylic acid analogues is dependent on P3' group chirality.
Structure-activity relationships are described for a series of succinyl hydroxamic acids 1a-o and their carboxylic acid analogues 2a-o as inhibitors of matrix metalloproteases MMP-3 and MMP-2. For this series (P1' = (CH2)3Ph, P2' = t-Bu) selectivity for the inhibition of MMP-2 was found to be strongly dependent on P3'.
Fray
M J
MJ
Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich, Kent, UK. jonathan_fray@sandwich.pfizer.com
Burslem
M F
MF
Dickinson
R P
RP
D006877:Hydroxamic Acids / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors