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.
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.
Stock
Nicholas
N
Amira Pharmaceuticals, San Diego, CA 92121, USA. nick.stock@amirapharm.com
Baccei
Christopher
C
Bain
Gretchen
G
Chapman
Charles
C
Correa
Lucia
L
Darlington
Janice
J
King
Christopher
C
Lee
Catherine
C
Lorrain
Daniel S
DS
Prodanovich
Pat
P
Santini
Angelina
A
Schaab
Kevin
K
Evans
Jilly F
JF
Hutchinson
John H
JH
Prasit
Peppi
P
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
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