title: 5-Lipoxygenase-activating protein inhibitors. Part 3: 3-{3-tert-Butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid (AM643)-A potent FLAP inhibitor suitable for topical administration.
abstract: AM643 (compound 6, 3-{3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid) was identified as a potential candidate for formulation as a topical agent for the treatment of skin disorders involving leukotriene production. Dermal application of 6 using a prototypical vehicle in a murine ear arachidonic acid model showed significant reduction in the concentrations of leukotrienes in mouse skin with concomitant reduction in ear swelling.
authors.affiliation: Amira Pharmaceuticals, San Diego, CA 92121, USA. nick.stock@amirapharm.com
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stock
authors.forename: Christopher
authors.initials: C
authors.lastname: Baccei
authors.forename: Gretchen
authors.initials: G
authors.lastname: Bain
authors.forename: Charles
authors.initials: C
authors.lastname: Chapman
authors.forename: Lucia
authors.initials: L
authors.lastname: Correa
authors.forename: Janice
authors.initials: J
authors.lastname: Darlington
authors.forename: Christopher
authors.initials: C
authors.lastname: King
authors.forename: Catherine
authors.initials: C
authors.lastname: Lee
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Lorrain
authors.forename: Pat
authors.initials: P
authors.lastname: Prodanovich
authors.forename: Angelina
authors.initials: A
authors.lastname: Santini
authors.forename: Kevin
authors.initials: K
authors.lastname: Schaab
authors.forename: Jilly F
authors.initials: JF
authors.lastname: Evans
authors.forename: John H
authors.initials: JH
authors.lastname: Hutchinson
authors.forename: Peppi
authors.initials: P
authors.lastname: Prasit
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins / Q000378:metabolism; D000287:Administration, Topical; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D015289:Leukotrienes / Q000096:biosynthesis; D051379:Mice; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D051381:Rats; D012871:Skin Diseases / Q000139:chemically induced / Q000188:drug therapy
chemical_list: C553440:3-(3-tert-butylsulfanyl-1-(4-(5-methoxy-pyrimidin-2-yl)-benzyl)-5-(5-methyl-pyridin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethyl-propionic acid; D058927:5-Lipoxygenase-Activating Proteins; D004791:Enzyme Inhibitors; D007211:Indoles; D015289:Leukotrienes; D011422:Propionates