Conformationally restricted aromatic inhibitors of...

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C - Chemistry, Metallurgy

07

C

C07C 233/57 (2006.01) A61K 31/045 (2006.01) A61K 31/10 (2006.01) A61K 31/11 (2006.01) A61K 31/12 (2006.01) A61K 31/16 (2006.01) A61K 31/191 (2006.01) A61K 31/215 (2006.01) A61K 31/275 (2006.01) A61K 31/33 (2006.01) A61K 31/366 (2006.01) A61K 31/404 (2006.01) A61K 31/4468 (2006.01) A61K 31/66 (2006.01) A61K 31/695 (2006.01) C07C 17/093 (2006.01) C07C 33/34 (2006.01) C07C 47/453 (2006.01) C07C 49/563 (2006.01) C07C 49/567 (2006.01) C07C 49/573 (2006.01) C07C 69/00 (2006.01) C07C 69/753 (2006.01) C07C 205/11 (

Patent

CA 2236684

Novel compounds are provided which are inhibitors of MTP and thus are useful for lowering serum lipids and treating atherosclerosis and related diseases, and have the structure (I) or (IA) or (IB) including pharmaceutically acceptable salts thereof or prodrug esters thereof, wherein q is 0,1 or 2; Rx is H, alkyl, aryl or halogen; A is (1) a bond; (2) -O-; or (3) (i); B is: (ii) or (iii) or (iv) or (v) (wherein (a = 2, 3 or 4)) or (vi) or (vii) or (viii); and wherein L2, L1, R1, R2, R3, R3', R3a, R3b, R4, R4', R5, X, (ix), (x) and (xi) are as defined herein.

Cette invention se rapporte à de nouveaux composés qui sont des inhibiteurs de la protéine de transfert de triglycéride microsomique (MTP) et qui sont par conséquent utiles pour abaisser la teneur en lipides du sérum et pour traiter l'athérosclérose et les maladies apparentées, ces composés ayant la structure (I) ou (IA) ou (IB), ainsi qu'à des sels pharmaceutiquement acceptables de ces composés ou à des esters promédicaments de ces composés. Dans ces formules, q est égal à 0, à 1 ou à 2; R?x¿ représente H, alkyle, aryle ou halogène; A représente (1) une liaison; (2) -O-; ou (3) (i); B représente (ii) ou (iii) ou (iv) ou (v) (où (a = 2, 3 ou 4)) ou (vi) ou (vii) ou (viii); et L?2¿, L?1¿, R?1¿, R?2¿, R?3¿, R?3'¿, R?3a¿, R?3b¿, R?4¿, R?4'¿, R?5¿, X, (ix), (x) et (xi) sont tels que définis dans les pièces descriptives de l'invention.

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