4,4-disubstituted-3,4-dihydro-2(1h)-quinazolinthione...

C - Chemistry – Metallurgy – 07 – D

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C07D 239/78 (2006.01) A61K 31/505 (2006.01) C07D 239/00 (2006.01) C07D 317/00 (2006.01) C07D 401/06 (2006.01) C07D 403/06 (2006.01) C07D 405/06 (2006.01) C07D 409/06 (2006.01) C07D 413/06 (2006.01) C07D 417/06 (2006.01) C07D 491/04 (2006.01)

Patent

CA 2322203

The present invention relates to 4,4-disubstituted-3,4-dihydro-2(1H)- quinazolinthiones of formula (I), wherein: R1 is C1-3 alkyl substituted with 1- 7 halogen; R2 is selected from C1-5 alkyl substituted with 1-2 R4, C2-5 alkenyl substituted with 1-2 R4, and C2-5 alkynyl substituted with 1 R4; R4 is selected from C3-5 cycloalkyl substituted with 0-2 R3, phenyl substituted with 0-5 R3, and a 5- 6-membered heterocyclic system containing 1-3 heteroatoms selected from O, N, and S, substituted with 0-2 R3; and compounds of formula (II), wherein R2 is CC-R4a; R4a is selected from methyl, ethyl, n-propyl, i- propyl, i-butyl, t-butyl, and i-pentyl; R3 at each occurrence, is independently selected from C1-4 alkyl, OH, C1-4 alkoxy, F, Cl, Br, I, NR5R5a, NO2, CN, C(O)R6, NHC(O)R7, and NHC(O)NR5R5a; alternatively, if two R3's are present and are attached to adjacent carbons, then they may combine to form - OCH2O-; R8 is selected from H, C3-5 cycloalkyl, and C1-3 alkyl; and n is selected from 0, 1, 2, 3, and 4 or stereoisomeric forms, stereoisomeric mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same, and methods of using the same for treating viral infection or as an assay standard or reagent.

L'invention porte sur des 3,4-dihydro-2(1H)-quinazolinthiones substitués en 4,4, de formule (I) dans laquelle R?1¿ représente alkyle C¿1-3? substitué par halogène 1-7; R?2¿ est choisi parmi alkyle C¿1-5? substitué par 1-2R?4¿, alcényle C¿2-5? substitué par 1-2 R?4¿ et alcynyle C¿2-5? substitué par 1R?4¿; R?4¿ est choisi parmi cycloalkyle C¿3-5? substitué par O-2 R?3¿, phényle substitué par 0-5 R?3¿, et un système hétérocyclique à 5 à 6 éléments, contenant 1-3 hétéroatomes, choisi parmi O, N et S, substitué par 0-2 R?3¿; et sur des composés de formule (II) dans laquelle R?2¿ représente C?C-R?4a¿; R?4a¿ est choisi parmi méthyle, éthyle, n-propyle, i-propyle, i-butyle, t-butyle et i-pentyle; R?3¿, à chaque apparition, est choisi séparément parmi alkyle C¿1-4?, OH, alcoxy C¿1-4?, F, Cl, Br, I, NR?5¿R?5a¿, NO¿2?, CN, C(O)R?6¿, NHC(O)R?7¿, et NHC(O)NR?5¿R?5a¿; ou, si deux R?3'¿ sont présents et sont rattachés à des carbones adjacents, ils peuvent alors se combiner pour former OCH¿2?O-; R?8¿ est choisi parmi H, cycloalkyle C¿3-5?, et alkyle C¿1-3?; et n est choisi parmi 0, 1, 2, 3 et 4; ou sur des formes stéréoisomères, des mélanges stéréoisomères ou sur des formes de sels desdits composés, acceptables au plan pharmaceutique, utiles en tant qu'inhibiteurs de la transcriptase inverse du VIH, sur des compositions pharmaceutiques, sur des kits de diagnostic les contenant, sur des méthodes d'utilisation de ceux-ci pour le traitement de l'infection virale ou comme réactif ou témoin d'essai.

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