Abstract: Described herein are methods for rational design of inhibitors of HIV-1 protease, and crystal structures of HIV-1 protease inhibitors bound to HIV-1 protease.

Abstract: The invention concerns novel mutations or mutational profiles of HIV-1 protease cleavage sites (CS) in the Gag region correlated with a phenotype causing alterations in sensitivity to anti-HIV drugs. The present invention also relates to the use of genotypic characterization of a target population of HIV and the subsequent association, i.e. correlation, of this information to phenotypic interpretation in order to correlate virus mutational profiles with drug resistance. The invention further relates to methods of utilizing the mutational profiles of the invention in databases, drug development, i.e., drug design, and drug modification, therapy and treatment design and clinical management.

Abstract: The present invention relates to 5H-pyrazolo[1,5-c][1,3]benzoxazin-5-yl)phenyl methanone derivatives as inhibitors of the viral replication of the HIV virus, processes for their preparation as well as pharmaceutical compositions, their use as medicines, and diagnostic kits comprising them. The present invention also concerns combinations of the present HIV inhibitors with other anti-retroviral agents. It further relates to their use in assays as reference compounds or as reagents. The compounds of the present invention are useful for preventing or treating infection by HIV and for treating AIDS.

Abstract: This invention relates to powders for reconstitution comprising the NNRTI TMC278 dispersed in certain water-soluble polymers, which can be used in the treatment of HIV infection.

Abstract: Compounds of the Formula (I) including a stereoisomer thereof, or an N-oxide, a pharmaceutically acceptable addition salt, or a pharmaceutically acceptable addition solvate thereof; useful as HCV inhibitors; processes for preparing these compounds as well as pharmaceutical compositions comprising these compounds as active ingredient.

Abstract: New pseudopolymorphic forms of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl(1S,2R)-3-[[(4-aminophenyl)sulfonyl](isobutyl)amino]-1-benzyl-2-hydroxypropylcarbamate and processes for producing them are disclosed.

Abstract: Methods for the preparation of hexahydrofuro[2,3-b]furan-3-ol and especially its enantiomer (3R,3aS,6aR) hexahydrofuro[2,3-b]furan-3-ol, as well as certain novel intermediates for use in such methods.

Abstract: Inhibitors of HCV replication of formula (I) and the N-oxides, salts, or stereoisomers thereof, wherein each dashed line (represented by - - - - -) represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is —OR6, —NH—SO2R7; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, or C3-7cycloalkyl; n is 3, 4, 5, or 6; R4 and R5 independently from one another are hydrogen, halo, hydroxy, nitro, cyano, carboxyl, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, C1-6alkylcarbonyl, C1-6alkoxy-carbonyl, amino, azido, mercapto, C1-6alkylthio, polyhaloC1-6alkyl, aryl or Het; W is aryl or Het; R6 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R7 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; aryl is phenyl or naphthyl, each optio

Abstract: 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 C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, 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 C1-6alkyl; L is —C(?O)—, —O—C(?O)—, —NR8—C(?O)—, —O—C1-6alkanediyl-C(?O)—, —NR8—C1-6alkanediyl-C(?O)—, —S(?O)2—, —O—S(?O)2—, —NR8—S(?O)2; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(?O), carboxyl, aminoC(?O), mono- or di(C1-4alkyl)aminoC(?O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; A is C1-6alkanediyl, —C(?O)—, —C(?S)—, —S(?O)2—, C1-6alkanediyl-C(?O)—, C1-6alkanediyl-C(?S)— or C1-6alkanediyl-S(?O)2—; R5 is H, OH, C1-6alkyl, Het1C1-6alkyl, Het2C1-6alkyl, optionally substituted aminoC1-6alkyl; R6 is C1-6alkylO, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6

Abstract: Compounds of the formula I: and N-oxides, salts, and stereoisomers thereof wherein A is OR1, NHS(?O)pR2; wherein; R1 is hydrogen, C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkylene-heterocyclyl; R2 is C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl; p is independently 1 or 2; n is 3, 4, 5 or 6; denotes an optional double bond; L is N or CRz; Rz is H or forms a double bond with the asterisked carbon; Rq is H or when L is CRz, Rq can also be C1-C6alkyl; Rr is quinazolinyl, optionally substituted with one two or three substituents each independently selected from C1-C6 alkyl, C1-C6alkoxy, hydroxyl, halo, haloC1-C6alkyl, amino, mono- or dialkylamino, mono- or dialkylaminocarbonyl, C1-C6alkyl-carbonylamino, C0-C3alkylenecarbocyclyl and C0-C3 alkyleneheterocyclyl; R5 is hydrogen, C1-C6alkyl, C1-C6alkoxyC1-C6alkyl or C3-C7cycloalkyl; R6 is hydrogen, C1-C6alkyl, C1-C6alkoxy, C0-C3alkylenecarbocyclyl, C0-C3alkylene-heterocyclyl, hydroxy, bromo, chloro or fluoro have utility in the treatme

Abstract: 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 C1-6alkyl, C2-6alkenyl, 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 C1-6alkyl; L is —C(?O)—, —O—C(?O)—, —NR8—C(?O)—, —C1-6alkanediyl-C(?O)—, —NR8—C1-6alkanediyl-C(?O)—, —S(?O)2—, —O—S(?O)2—, —NR9-S(?O)2; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(?O), carboxyl, aminoC(?O), mono- or di(C1-4alkyl)aminoC(?O), C3-7 cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; R5 and R6 are H or C1-6alkyl. 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.

Abstract: This invention concerns the compounds the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein X is NR2, O, S, SO, SO2; R1 is hydrogen, cyano, halo, substituted carbonyl, methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; n is 1, 2 or 3; R2 is hydrogen, aryl substituted with a radical —COOR4; or R2 is substituted C1-10alkyl, C2-20alkenyl or C3-7cycloalkyl; or R2 is a radical of formula: —CpH2p—CH(OR14)—CqH2q—R15 (b-3); —CH2—CH2—(O—CH2—CH2)m—OR14 (b-4); —CH2—CH2—(O—CH2—CH2)m—NR5aR5b (b-5); -a1=a2-a3=a4- is —CH?CH—CH?CH—; —N?CH—CH?CH—; —CH?N—CH?CH—; —CH?CH—N?CH—; —CH?CH—CH?N— (c-5); wherein one of the hydrogen atoms in (c-1)-(c-5) is replaced by particular radicals; R3 is nitro, cyano, amino, halo, hydroxy, C1-4alkyloxy, hydroxycarbonyl, substituted carbonyl, methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het1.

Abstract: 1-heterocyclyl-1,5-dihydro-pyrido[3,2-b]indol-2-ones of formula (I): the N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites thereof, wherein n is 1, 2 or 3; R1 is hydrogen, cyano, halo, substituted carbonyl, methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; X is NR2, O, S, SO, SO2; R2 is hydrogen, C1-10alkyl, C2-10alkenyl, C3-7cycloalkyl, which are optionally substituted; R2 is aryl substituted with —COOR4; or R2 is: —CpH2p—CH(OR14)—CqH2q—R15 ??(b-3); —CH2—CH2—(O—CH2—CH2)m—OR14 ??(b-4); —CH2—CH2—(O—CH2—CH2)m—NR5aR5b (b-5); -a1=a2-a3=a4- is —CH?CH—CH?CH—; —N?CH—CH?CH—; —CH?N—CH?CH—; —CH?CH—N?CH—; —CH?CH—CH?N—; wherein hydrogen atoms in (c-1)-(c-5) may be replaced by certain radicals; R3 is a monocyclic or bicyclic aromatic heterocyclic ring system that can be substituted.

Abstract: The present invention concerns the compounds of formula (I) their N-oxides, salts, stereoisomeric forms, racemic mixtures, prodrugs, esters and metabolites, wherein n is 1, 2 or 3; R1is H, CN, halo, aminoC(?O), C(?O)OH, C1-4alkyloxyC(?O), C1-4alkylC(?O), mono- or di(C1-4alkyl)aminoC(?O), arylaminoC(?O), N-(aryl)-N—(C1-4alkyl)aminoC(?O), methanimidamidyl, N-hydroxy-methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, Het1 or Het2; R2 is H, C1-10alkyl, C2-10alkenyl, C3-7cycloalkyl, wherein said C1-10alkyl, C2-10alkenyl and C3-7cycloalkyl may be optionally substituted; R3 is nitro, cyano, amino, halo, hydroxy, C1-4alkyloxy, hydroxyC(?O), aminoC(?O), C1-4alkyloxyC(?O), mono- or di(C1-4alkyl)aminoC(?O), C1-4alkylC(?O), methanimidamidyl, mono- or di(C1-4alkyl)methanimidamidyl, N-hydroxy-methanimidamidyl or Het1; for use as a medicine. The invention further relates to a novel subgroup of the compounds of formula (I), and to compositions comprising compounds of formula (I).

Abstract: The present invention relates to methods for the preparation of diastereomerically pure (3R,3aS,6aR) hexahydro-furo[2,3-b]furan-3-ol as well as a novel intermediate, (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan-2-one for use in said methods. More in particular the invention relates to a stereoselective method for the preparation of diastereomerically pure (3R,3aS,6aR) hexahydro-furo[2,3-b]furan-3-ol, as well as methods for the crystallization of (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan-2-one and for the epimerization of (3aR,4R,6aS) 4-methoxy-tetrahydro-furo[3,4-b]-furan-2-one to (3aR,4S,6aS) 4-methoxy-tetrahydro-furo[3,4-b]furan-2-one.

Abstract: 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 C1-6alkyl, C2-6alkenyl, C3-7cycloalkyl, 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 C1-6alkyl; L is —C(?O)—, —O—C(?O)—, —NR8—C(?O)—, —O—C1-6alkanediyl-C(?O)—, —NR8—C1-6alkanediyl-C(?O)—, —S(?O)2—, —O—S(?O)2—, —NR8—S(?O)2; R3 is C1-6alkyl, aryl, C3-7cycloalkyl, C3-7cycloalkylC1-4alkyl, or arylC1-4alkyl; R4 is H, C1-4alkylOC(?O), carboxyl, aminoC(?O), mono- or di(C1-4alkyl)aminoC(?O), C3-7cycloalkyl, C2-6alkenyl, C2-6alkynyl or optionally substituted C1-6alkyl; A is C1-6alkanediyl, —C(?O)—, —C(?S)—, —S(?O)2—, C1-6alkanediyl-C(?O)—, C1-6alkanediyl-C(?S)— or C1-6alkanediyl-S(?O)2—; R5 is H, OH, C1-6alkyl, Het1C1-6alkyl, Het2C1-6alkyl, optionally substituted aminoC1-6alkyl; R6 is C1-6alkylO, Het1, Het1O, Het2, Het2O, aryl, arylO, C1-6

Abstract: This invention relates to a process for producing a spray-dried powder comprising microcrystalline cellulose in a solid dispersion of the anti-HIV compound etravirine (TMC125) in a water-soluble polymer.

Abstract: The present invention relates to the use of pteridines as inhibitors of HCV replication as well as their use in pharmaceutical compositions aimed to treat or combat HCV infections. In addition, the present invention relates to compounds per se and their use as medicines. The present invention also concerns processes for the preparation of such compounds, pharmaceutical compositions comprising them, and combinations of said compounds with other anti-HCV agents.

Abstract: The present invention relates to the use of pyrido[2,3-d]pyrimidines as inhibitors of HCV replication as well as their use in pharmaceutical compositions aimed to treat or combat HCV infections. In addition, the present invention relates to pyrido-[2,3-d]pyrimidines compounds per se and their use as medicines. The present invention also concerns processes for the preparation of such compounds, pharmaceutical compositions comprising them, and combinations of said compounds with other anti-HCV agents.

Abstract: HIV replication inhibitors of formula (I) N-oxides, a pharmaceutically acceptable addition salts, a quaternary amines or a stereoisomeric forms thereof, wherein -a1=a2-a3=a4- is —CH?CH—CH?CH—, —N?CH—CH?CH—, —N?CH—N?CH—, —N?CH—CH?N—, —N?N—CH?CH—; -b1=b2-b3=b4- is —CH?CH—CH?CH—, —N?CH—CH?CH—, —N?CH—N?CH—, —N?CH—CH?N—, —N?N—CH?CH—; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; optionally substituted C1-6alkyl; C1-6alkyloxycarbonyl; R2 is OH; halo; optionally substituted C1-6alkyl, C2-6alkenyl or C2-6alkynyl; substituted carbonyl; carboxyl; CN; nitro; amino; substituted amino; polyhalomethyl; polyhalomethylthio; —S(?O)rR6; C(?NH)R6; R2a is CN; amino; substituted amino; optionally substituted C1-6alkyl; halo; optionally substituted C2-6alkyloxy; substituted carbonyl; —CH?N—NH—C(?O)—R16; optionally substituted C1-6alkyloxy C1-6alkyl; substituted C2-6alkenyl or C2-6alkynyl; —C(?N—O—R8)—C1-4alkyl; R7 or —X3—R7; X1 is —NR1—, —O—, —C(?O)—, CH2, —CHOH—, —S—, —S(?O)r—; R3 is CN; amino; C1-6alkyl; halo; optionally subs