C - Chemistry – Metallurgy – 07 – D
Patent
C - Chemistry, Metallurgy
07
D
C07D 211/40 (2006.01) A61K 31/395 (2006.01) C07D 207/12 (2006.01) C07D 211/46 (2006.01) C07D 221/20 (2006.01) C07D 223/08 (2006.01) C07D 225/02 (2006.01) C07D 401/00 (2006.01) C07D 403/00 (2006.01) C07D 405/00 (2006.01) C07D 409/00 (2006.01) C07D 413/00 (2006.01) C07D 417/00 (2006.01)
Patent
CA 2192459
Compounds which inhibit the enzyme cholesterol ester hydrolase (CEH) thus inhibit the formation of esterified cholesterol. Esterified cholesterol is absorbed through the intestine and inhibition of the enzyme therefore results in inhibition of cholesterol absorption. The compounds of this invention inhibit cholesterol ester hydrolase and have formula (I), wherein Z is -Ar1, - Ar1-Ar2, -Ar1-O-Ar2, -Ar1-S-Ar2, (a), (b), (c), -Ar1-(CH2)1-20-Ar2, -Ar1- (CH2)1-20-O-Ar2, -Ar1-O-(CH2)1-20-Ar2, -Ar1-(CR6=CR6)1-3-Ar2 or -Ar1-NR7-Ar2; and A is a hydrocarbon linking group which may be interrupted by a heteroatom or a cycloalkyl, aryl, heterocycloalkyl, or an azacycloalkyl group; and R4 and R5 are independently alkyl, alkenyl, acyl, alkoxycarbonyl or H or R4 and R5 together with the interposed nitrogen form a saturated heterocyclic ring.
L'invention se rapporte à des composés qui inhibent l'hydrolase de l'ester de cholestérol ainsi que la formation de cholestérol estérifié. Le cholestérol estérifié est absorbé par l'intestin et l'inhibition de l'enzyme entraîne par conséquent l'inhibition de l'absorption du cholestérol. Les composés de cette invention inhibent l'hydrolase de l'ester de cholestérol et ont la formule (I) dans laquelle Z représente -Ar?1¿, -Ar?1¿-Ar?2¿,-Ar?1¿-O-Ar?2¿,-Ar?1¿-S-Ar?2¿, (a), (b), (c), Ar?1¿-(CH¿2?)¿1-20?-Ar?2¿, -Ar?1¿-(CH¿2?)¿1-20?-O-Ar?2¿, -Ar?1¿-O-(CH¿2?)¿1-20?-Ar?2¿, -Ar?1¿-(CR?6¿=CR?6¿)¿1-3?-Ar?2¿ ou -Ar?1¿-NR?7¿-Ar?2¿; et A représente un groupe de liaison d'hydrocarbure qui peut être interrompu par un hétéroatome ou un cycloalkyle, aryle, hétérocycloalkyle, ou un groupe azacycloalkyle; et R?4¿ et R?5¿ représentent, indépendamment, alkyle, alcényle, acyle, alcoxycarbonyle ou H ou R?4¿ et R?5¿ conjointement avec l'azote intercalé forme un noyau hétérocyclique saturé.
Commons Thomas Joseph
Laclair Christa Marie
American Home Products Corporation
Ridout & Maybee Llp
LandOfFree
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