BROADSPECTRUM 2-(SUBSTITUTED-AMINO)-BENZOXAZOLE SULFONAMIDE HIV PROTEASE INHIBITORS

摘要

The present invention concerns the compounds having the formula N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein R₁ and R₈ each are H, optionally substituted C_1-6alkyl, C_2-6alkenyl, C_3-7cycloalkyl, aryl, Het¹, Het²; R₁ may also be a radical of formula (R_11aR_11b)NC(R_10aR_10b)CR₉-; t is 0, 1 or 2; R₂ is H or C_1-6alkyl; L is -C(-O)-, -O-C(-O)-, -NR₈-C(-O)-, -O-C_1-6alkanediyl-C(-O)-, -NR₈-C_1-6alkanediyl-C(-O)-, -S(-O)₂-, -O-S(-O)₂-, -NR₈-S(-O)₂; R₃ is C_1-6alkyl, aryl, C_3-7cycloalkyl, C_3-7cycloalkylC_1-4alkyl, or arylC_1-4alkyl; R₄ is H, C_1-4alkylOC(-O), carboxyl, aminoC(-O), mono- or di(C_1-4alkyl)aminoC(-O), C_3-7cycloalkyl, C_2-6alkenyl, C_2-6alkynyl or optionally substituted C_1-6alkyl; A is C_1-6alkanediyl, -C(-O)-, -C(-S)-, -S(-O)₂-, C_1-6alkanediyl-C(-O)-, C_1-6alkanediyl-C(-S)- or C_1-6alkanediyl-S(-O)₂-; R₅ is H, OH, C_1-6alkyl, Het¹C_1-6alkyl, Het²C_1-6alkyl, optionally substituted aminoC_1-6alkyl; R₆ is C_1-6alkylO, Het¹, Het¹O, Het², Het²O, aryl, arylO, C_1-6alkyloxycarbonylamino or amino; and in case -A- is other than C_1-6alkanediyl then R₆ may also be C_1-6alkyl, Het¹C_1-4alkyl, Het¹OC_1-4alkyl, Het²C_1-4alkyl, Het²OC_1-4alkyl, arylC_1-4alkyl, arylOC_1-4alkyl or aminoC_1-4alkyl; whereby each of the amino groups in the definition of R₆ may optionally be substituted; -A-R₆ is hydroxyC_1-6alkyl; R₅ and -A-R₆ taken together with the nitrogen atom to which they are attached may also form Het¹ or Het². It further relates to their use as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them. It also concerns combinations thereof with another anti-retroviral agent, and to their use in assays as reference compounds or as reagents.