title: The discovery and development of selective 3-fluoro-4-aryloxyallylamine inhibitors of the amine oxidase activity of semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1).
abstract: A new class of 3-fluoroallyl amine-based SSAO/VAP-1 inhibitors is reported. These compounds have excellent selectivity over diamine oxidase, MAO-A and MAO-B. Synthesis and SAR studies leading to compound 28 (PXS-4159A) are reported. The pharmacokinetic profile of 28 in the rat, together with activity in a murine model of lung inflammation are also disclosed.
authors.affiliation: Pharmaxis Ltd., 20 Rodborough Road, Frenchs Forest, NSW 2086, Australia. jonathan.foot@pharmaxis.com.au
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Foot
authors.forename: Mandar
authors.initials: M
authors.lastname: Deodhar
authors.forename: Craig I
authors.initials: CI
authors.lastname: Turner
authors.forename: Ping
authors.initials: P
authors.lastname: Yin
authors.forename: Ellen M
authors.initials: EM
authors.lastname: van Dam
authors.forename: Diego G
authors.initials: DG
authors.lastname: Silva
authors.forename: Aldo
authors.initials: A
authors.lastname: Olivieri
authors.forename: Andrew
authors.initials: A
authors.lastname: Holt
authors.forename: Ian A
authors.initials: IA
authors.lastname: McDonald
mesh_terms: D000498:Allyl Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000588:Amines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D055808:Drug Discovery; D054879:Halogenation; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011014:Pneumonia / Q000188:drug therapy* / Q000201:enzymology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000498:Allyl Compounds; D000588:Amines; D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D006631:Amine Oxidase (Copper-Containing)