title: Synthesis and biological activity of piperazine-based dual MMP-13 and TNF-alpha converting enzyme inhibitors.
abstract: A series of novel MMP-13 and TNF-alpha converting enzyme inhibitors based on piperazine 2-hydroxamic acid scaffolds are described. The TACE, MMP-1 and MMP-13 activity of these inhibitors as well as the effect of substitution of the piperazine nitrogen and the P-1' benzyloxy tailpiece is discussed. Moderate in vivo activity is observed with several members of this group.
authors.affiliation: Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. michael_a_letavic@groton.pfizer.com
authors.forename: Michael A
authors.initials: MA
authors.lastname: Letavic
authors.forename: John T
authors.initials: JT
authors.lastname: Barberia
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Carty
authors.forename: Joel R
authors.initials: JR
authors.lastname: Hardink
authors.forename: Jennifer
authors.initials: J
authors.lastname: Liras
authors.forename: Lori L
authors.initials: LL
authors.lastname: Lopresti-Morrow
authors.forename: Peter G
authors.initials: PG
authors.lastname: Mitchell
authors.forename: Mark C
authors.initials: MC
authors.lastname: Noe
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Reeves
authors.forename: Sheri L
authors.initials: SL
authors.lastname: Snow
authors.forename: Ethan J
authors.initials: EJ
authors.lastname: Stam
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Sweeney
authors.forename: Marcie L
authors.initials: ML
authors.lastname: Vaughn
authors.forename: Chul H
authors.initials: CH
authors.lastname: Yu
mesh_terms: D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D017364:Collagenases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D010879:Piperazines; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; D008666:Metalloendopeptidases; C507083:Mmp13 protein, rat; D000072198:ADAM17 Protein; C000606464:Adam17 protein, rat