Fray M J, Dickinson R P
Department of Discovery Chemistry, Pfizer Global Research and Development, Sandwich, Kent, UK.
Bioorg Med Chem Lett. 2001 Feb 26;11(4):571-4. doi: 10.1016/s0960-894x(00)00720-4.
Structure activity relationships are described for a series of succinyl hydroxamic acids 4a-o as potent and selective inhibitors of matrix metalloprotease-3 (stromelysin-1). Optimisation of P1' and P3' groups gave compound 4j (MMP-3 IC50=5.9nM) which was >140-fold less potent against MMP-1 (IC50=51,000nM), MMP-2 (IC50=1790nM), MMP-9 (IC50=840nM) and MMP-14 (IC50=1900nM).
描述了一系列琥珀酰异羟肟酸4a - o作为基质金属蛋白酶-3（基质溶解素-1）的有效和选择性抑制剂的构效关系。对P1'和P3'基团进行优化得到化合物4j（MMP - 3的IC50 = 5.9 nM），其对MMP - 1（IC50 = 51,000 nM）、MMP - 2（IC50 = 1790 nM）、MMP - 9（IC50 = 840 nM）和MMP - 14（IC50 = 1900 nM）的活性低140倍以上。
