Hiv-integrase inhibitors, pharmaceutical compositions, and...

C - Chemistry – Metallurgy – 07 – D

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C07D 471/04 (2006.01) A61K 31/437 (2006.01) A61P 31/18 (2006.01)

Patent

CA 2513141

Beta-carboline hydroxamic acid compounds represented by formula (I) and formula (lb) are described, wherein: R1, R2, R3, R4, R5, and R6 are independently selected from hydrogen, halogen, C1_C6 alkyl, aikoxy C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, -ORc, -NO2, and -N(Rc)2, each Rc is Independently selected from hydrogen, C1-C6 alkyl, C2-C6 alkenyl, and C2-Ca alkynyl; R7 Is C1-C6 alkyl, C2-C6 alkenyl, or C2-C6 alkynyl, all of which are optionally substituted by one or more substituents independently selected from halogen, C1-C6 alkyl, C2-C6 alkenyl; C2-C6 alkynyl, aryl, cycloalkyl, heterocycioalkyl, and heteroaryl, wherein said aryl, cydoalkyi, and heterocycloalkyl are optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl; R8 and R9 are independently selected from hydrogen, C1-C6 alkyl, C2- C6 alkenyl, and C2-C6 aikynyl, wherein said alkyl, alkenyl, and alkynyl are optionally substituted with one or more substituents independently selected from halogen, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl group, wherein said aryl, cycloalkyl, and heterocycloalkyl are optionally substituted with one or more substituents independently selected from halogen, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl. The beta-carboline hydroxamic acid compounds and compositions containing those compounds may be used to inhibit or modulate the activity of HIV integrase enzyme and to treat HIV integrase- mediated diseases and conditions.

Composés d'acide hydroxamique et de bêta-carboline représentés par les formules (I) et (lb) dans lesquelles R¿1,? R¿2?, R¿3?, R¿4?, R¿5? et R¿6? sont indépendamment choisis parmi hydrogène, halogène, alkyle C¿1?-C¿6?, alcoxyalkyle C¿1?-C¿6?, alcényle C¿2?-C¿6?, alcynyle C¿2?-C¿6?, -OR¿c?, -NO¿2? et -N(R¿c?)¿2?; chaque R¿c? est indépendamment choisi parmi hydrogène, alkyle C¿1?-C¿6?, alcényle C¿2?-C¿6? et alcynyle C¿2?-C¿6 ?; R¿7? représente alkyle C¿1?-C¿6?, alcényle C¿2?-C¿6? ou alcynyle C¿2?-C¿6?, tous étant éventuellement substitués par un ou plusieurs substituants indépendamment choisis parmi halogène, alkyle C¿1?-C¿6?, alcényle C¿2?-C¿6?, alcynyle C¿2?-C¿6?, aryle, cycloalkyle, hétérocycloalkyle et hétéroaryle, lesdits aryle, cycloalkyle et hétérocycloalkyle étant éventuellement substitués par un ou plusieurs substituants choisis indépendamment parmi halogène, alkyle C¿1?-C¿6?, alcényle C¿2?-C¿6? et alcynyle C¿2?-C¿6 ;? R¿8? et R¿9? sont indépendamment choisis parmi hydrogène, alkyle C¿1?-C¿6?, alcényle C¿2?-C¿6? et alcynyle C¿2?-C¿6?, lesdits alkyle, alcényle et alcynyle étant éventuellement substitués par un ou plusieurs substituants choisis indépendamment parmi halogène, un groupe aryle, cycloalkyle, hétérocycloalkyle et hétéroaryle, lesdits aryle, cycloalkyle et hétérocycloalkyle étant éventuellement substitués par un ou plusieurs substituants choisis indépendamment parmi halogène, alkyle C¿1?-C¿6?, alcényle C¿2?-C¿6? et alcynyle C¿2?-C¿6?. Lesdits composés d'acide hydroxamique et de bêta-carboline et les compositions les contenant peuvent être utilisés inhiber ou moduler l'activité de l'enzyme VIH-intégrase et pour traiter des maladies et états pathologiques induits par la VIH-intégrase.

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