title: Phosphinic acid-based MMP-13 inhibitors that spare MMP-1 and MMP-3.
abstract: Phosphinic acid-based inhibitors of MMP-13 have been investigated with the aim of identifying potent inhibitors with high selectivity versus MMP-1. Independent variation of the substituents on a P(1)' phenethyl group and a P(2) benzyl group improved potencies in both cases around 3-fold over the unsubstituted parent. Combining improved P(1)' and P(2) groups into a single molecule gave an inhibitor with a 4.5 nM IC(50) against MMP-13 and which is 270-fold selective over MMP-1.
authors.affiliation: Pfizer Inc, Global Reseach & Development, Groton Laboratories, Eastern Point Rd., 06340, Groton, CT, USA. lawrence_a_reiter@groton.pfizer.com
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Reiter
authors.forename: Peter G
authors.initials: PG
authors.lastname: Mitchell
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Martinelli
authors.forename: Lori L
authors.initials: LL
authors.lastname: Lopresti-Morrow
authors.forename: Sue A
authors.initials: SA
authors.lastname: Yocum
authors.forename: James D
authors.initials: JD
authors.lastname: Eskra
mesh_terms: D017364:Collagenases / Q000737:chemistry; D007202:Indicators and Reagents; D007536:Isomerism; D020781:Matrix Metalloproteinase 1 / Q000737:chemistry / Q000187:drug effects*; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3 / Q000737:chemistry / Q000187:drug effects*; D061965:Matrix Metalloproteinase Inhibitors; D010721:Phosphinic Acids / Q000737:chemistry* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D007202:Indicators and Reagents; D061965:Matrix Metalloproteinase Inhibitors; D010721:Phosphinic Acids; D011480:Protease Inhibitors; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1