Broadspectrum 2-(substituted-amino)-benzothiazole sulfonamide HIV protease inhibitors

摘要

Compounds having the formula (I), N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein: R1 and R8 each are H, optionally substituted C1-6 alkyl, C2-6 alkenyl, C3-7 cycloalkyl, aryl, Het1, Het2; R1 may also be a radical of formula (R11aR11b)NC(R10aR10b)CR9-; t is 0, 1 or 2; R2 is H or C1-6 alkyl; L is -C(=O)-, -O-C(=O)-, -NR8-C(=O)-, -O-C1-6 alkanediyl-C(=O)-, -NR8-C1-6 alkanediyl-C(=O)-, -S(=O)2-, -O-S(=O)2-, -NR8-S(=O)2; R3 is C1-6 alkyl, aryl, C3-7 cycloalkyl, C3-7 cycloalkylC1-4 alkyl, or arylC1-4 alkyl; R4 is H, C1-4 alkylOC(=O), carboxyl, aminoC(=O), mono- or di(C1-4 alkyl)aminoC(=O), C3-7 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl or optionally substituted C1-6 alkyl; A is C1-6 alkanediyl, -C(=O)-, -C(=S)-, -S(=O)2-, C1-6 alkanediyl-C(=O)-, C1-6 alkanediyl-C(=S)- or C1-6 alkanediyl-S(=O)2-; R5 is H, OH, C1-6 alkyl, Het1C1-6 alkyl, Het2C1-6 alkyl, optionally substituted aminoC1-6 alkyl; R6 is C1-6 alkylO, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6 alkyloxycarbonylamino or amino; and in case -A- is other than C1-6 alkanediyl then R6 may also be C1-6 alkyl, Het1C1-4 alkyl, Het1OC1-4 alkyl, Het2C1-4 alkyl, Het2OC1-4 alkyl, arylC1-4alkyl, arylOC1-4alkyl or aminoC1-4alkyl; whereby each of the amino groups in the definition of R6 may optionally be substituted; R5 and -A-R6 taken together with the nitrogen atom to which they are attached may also form Het1 or Het2. These use of the compounds of formula (I) as broadspectrum HIV protease inhibitors, processes for their preparation as well as pharmaceutical compositions and diagnostic kits comprising them is also disclosed, as well as combinations thereof with another anti-retroviral agent, and their use in assays as reference compounds or as reagents.