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

✍ Scribed by Nicholas Stock; Christopher Baccei; Gretchen Bain; Charles Chapman; Lucia Correa; Janice Darlington; Christopher King; Catherine Lee; Daniel S. Lorrain; Pat Prodanovich; Angelina Santini; Kevin Schaab; Jilly F. Evans; John H. Hutchinson; Peppi Prasit

• Book ID: 104004495
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 343 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.06.011

✦ Synopsis

AM643 (compound 6, 3-{3-tert-butylsulfanyl-1-[4-(5-methoxy-pyrimidin-2-yl)-benzyl]-5-(5-methylpyridin-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.