A novel orally active inhibitor of HLE.
Human leukocyte elastase (HLE) is a serine proteinase, capable of degrading a variety of structural matrix proteins. SSR69071 2-[(4-isopropyl-6-methoxy-1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methoxy]-9-(2-piperidin-1-ylethoxy)-4H-pyrido[1,2-a]pyrimidin-4-one was selected as a novel orally active HLE inhibitor for treatment of chronic obstructive pulmonary diseases, asthma, emphysema, cystic fibrosis and several inflammatory diseases (WO 01/44245 A1) (J. Pharm. Exp. Ther., submitted for publication).
Varga
Márton
M
Chinoin Co. Ltd - Member of Sanofi-Synthelabo Group, Discovery Research, H-1045, Tó utca 1-5, Budapest, Hungary, marton.varga@sanofi-synthelabo.com
Kapui
Zoltán
Z
Bátori
Sándor
S
Nagy
Lajos T
LT
Vasvári-Debreczy
Lelle
L
Mikus
Endre
E
Urbán-Szabó
Katalin
K
Arányi
Péter
P
D000284:Administration, Oral; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D003499:Cyclic S-Oxides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D019272:Leukocyte Elastase / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008173:Lung Diseases, Obstructive / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008956:Models, Chemical; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D003499:Cyclic S-Oxides; D004791:Enzyme Inhibitors; C474251:SSR 69071; D013844:Thiazoles; D019272:Leukocyte Elastase