Abstract: Compounds of the formula Z: where; A is CH or N; R1 is a substituent to a carbon atom in the ring containing A selected from —S(?O)pRa, where Ra is —C1-C4 alkyl, —ORx, —NRxRx, —NHNRxRx, —NHNHC(?O)ORx, —NRxOH; —C(?O)—Rb, where Rb is —CT-C4-alkyl, ORx, —NRxRx, —NHNRxRx, —NHC1-C3-alkyl-C(?O)Orx —NRxRc, where Rc is H, C1-C4 alkyl, —NRxRx; —C(=0)Rd, —CN, S(?O)pRx, where Rd is Rd is C1-C4-alkyl, —ORx, —NRxRx C1-C3-alkyl-O—C1-C3-alkylC(?O)ORx, —C1-C3-alkyl-COORx; —C1-C3alkyl-OH or C1-C4 alkyl ethers or esters thereof (O—C1-C3alkyl)q-O—Rx a 5 or 6 membered aromatic ring having 1-3 hetero atoms p is 1 or 2; Rx is independently selected from H, C1-C4 alkyl or acetyl; or a pair of Rx can together with the adjacent N atom form a ring; L is -0-, —S(?O)—, or —CH2—, where r is 0, 1 or 2; R3-R7 are substituents as defined in the specification; X is —(CR8R8?)n-D-(CR8R8?)m-; D is a bond, —NR9—, -0-, —S—, —S(=0)- or —S(=0)2-; and pharmaceutically acceptable salts and prodrugs thereof, have utility as HIV antivirals.

Abstract: Compounds of the formula II: wherein R2 is the side chain of leucine, isoleucine, cyclohexylglycine, O-methyl threonine, 4-fluoroleucine or 3-methoxyvaline; R3 is H, methyl or F; Rq is trifluoromethyl and Rq? is H or Rq and Rq? define keto; Q is a p-(C1-C6alkylsulphonyl)phenyl- or an optionally substituted 4-(C1-C6alkyl)piperazin-1-yl-thiazol-4-yl- moiety have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

Abstract: Compounds of the formula II: wherein R1 and R2 are independently H, F or CH3; or R1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo; R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and/or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro; R4 is methyl or fluoro; m is 0, 1 or 2; E is a bond, or thiazolyl, optionally substituted with methyl or fluoro; A1 is CH or N, A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N; R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4alkoxy or F; R7 is H, C1-C4 alkyl or F or a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteo

Abstract: Compounds of the formula (I) wherein: R1 is independently H1—OR3, —NHR4; C1-C4 alkyl; or, when n is 2, adjacent R1 together define an olefinic bond; R2 is H; or when the gem R1 is C1-C4 alkyl, that R2 may also be C1-C4 alkyl; or when the gem R1 is —OR3, that R2 may also be —C(?O)OH or a pharmaceutically acceptable ester thereof; R3 is independently H, or a pharmaceutically acceptable ester thereof; R4 is independently H or a pharmaceutically acceptable amide thereof; R5 and R6 are H or an amine prodrug moiety n is 1, 2 or 3; and pharmaceutically acceptable salts thereof; have utility in the treatment or prophylaxis of HIV, especially reverse transcriptase mutants which allow an obligate chain terminating nucleoside- or nucleotide phosphate to be excised from the nascent DNA strand by ATP- or pyrophosphate-mediated excision.

Abstract: Deoxyuridine derivatives of the formula where R1 is H or various substituents; D is —NHCO—, —CONH—, —O—, —C(?O)—, —CH?CH, —C?C—, —NR5—; R4 is hydrogen or various substituents; R5 is H, C1-C4 alkyl, C1-C4 alkanoyl; E is Si or C; R6, R7 and R8 are independently selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl or a stable monocyclic, bicyclic or tricyclic ring system; G is —O—, —S—, —CHR10—, —C(?O)—; J is —CH2—, or when G is CHR10 may also be —O— or —NH—; R10 is H, F, —CH3, —CH2NH2, —CH2OH, —OH; R11 is H, F, —CH3, —CH2NH2, —CH2OH, CH(OH)CH3, CH(NH2)CH3; or R10 and R11 together define an olefinic bond, or together form a —CH2-group, thereby defining a cis or trans cyclopropyl group; have utility in the prophylaxis or treatment of protozoal diseases such as malaria.

Abstract: 4-Amino-1-((2R,3S,4S,5R)-5-azido-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (22) and prodrugs thereof are hepatitis C (HCV) polymerase inhibitors. Also disclosed are compositions and methods for inhibiting HCV and treating HCV-mediated diseases, processes for making the compounds and synthetic intermediates employed in the process.

Abstract: There is provided inter alia use of 2?,3?-dideoxy-3?-hydroxymethylcytidine or a prodrug or salt thereof in the manufacture of a medicament for the treatment of HIV infection wherein the reverse transcriptase of the HIV bears at least one mutation that allows an obligate chain terminating nucleoside- or nucleotide phosphate to be excised from the nascent DNA strand by ATP- or pyrophosphate-mediated excision.

Abstract: 4-Amino-1-((2R,3S,4S,5R)-5-azido-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (22) and prodrugs thereof are hepatitis C(HCV) polymerase inhibitors. Also disclosed are compositions and methods for inhibiting HCV and treating HCV-mediated diseases, processes for making the compounds and synthetic intermediates employed in the process.

Abstract: A method for treatment of HBV and HIV infections comprising administering the compound or salt of formula Ig

Abstract: Compounds of the formula I: wherein R1, R2, X and N are as defined in the specification; E is N, CH; A? and A? are terminal groups as defined in the specification. The compounds have utility as HIV-1 protease inhibitors.

Abstract: Deoxyuridine derivatives of the formula (I) where R1 is H or various substituents; D is —NHCO—, —CONH—, -0-, —C(?O)—, —CH?CH, —C?C—, —NR5—; R4 is hydrogen or various substituents; R5 is H, C1-C4 alkyl, C1-C4 alkanoyl; E is Si or C; R6, R7 and R8 are independently selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl or a stable monocyclic, bicyclic or tricyclic ring system; G is —O—, —S—, —CHR10—, —C(?O)—; J is —CH2—, or when G is CHR10 may also be —O— or —NH—; R10 is H, F, —CH3, —CH2NH2, —CH2OH; —OHR11 is H, F, —CH3, —CH2NH2, —CH2OH, —CH(OH)CH3, CH(NH3)CH3; or R10 and R11 together define an olefinic bond, or together form a —CH2-group, thereby defining a cis or trans cyclopropyl group; have utility in the prophylaxis or treatment of protozoal diseases such as malaria.

Abstract: Methods drawn to peptidomimetic compounds which inhibit the NS3 protease of the hepatitis C virus (HCV), are described. The compounds have the formula (VI) where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

Abstract: 4-Amino-1-((2R,3S,4S,5R)-5-azido-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (22) and prodrugs thereof are hepatitis C(HCV) polymerase inhibitors. Also disclosed are compositions and methods for inhibiting HCV and treating HCV-mediated diseases, processes for making the compounds and synthetic intermediates employed in the process.

Abstract: Compounds of the formula (I): and N-oxides, salts and stereoisomers thereof wherein A is OR1, NHS(?O)pR2, NHR3, NRaRb, C(?O)NHR3 or C(?O)NRaRb wherein; R1 is hydrogen, C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl; R2 is C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl or NRaRb; R3 is C1-C6alkyl, C0-C3alkylenecarbocyclyl, C0-C3alkyleneheterocyclyl, —OC1-C6alkyl, —OC0-C3alkylenecarbocyclyl, —OC0-C3alkyleneheterocyclyl; wherein any alkyl, carbocyclyl or heterocycylyl in R1, R2 or R3 are optionally substituted p is independently 1 or 2; n is 3, 4, 5 or 6; denotes an optional double bond; Rq is H or when L is CRz, Rq can also be C1-C6alkyl; Ry and Ry? are independently C1-C6alkyl; L is N or CRz; Rz is H or forms a double bond with the asterisked carbon; W is —CH2—, —O—, —OC(?O)NH—, —OC(?O)—, —S—, —NH—, —NRa, —NHS(?O)2—, —NHC(=0)NH— or —NHC(?O)—, —NHC(?S)NH— or a bond; R8 is an optionally substituted ring system containing 1 or 2 saturated, partially saturated or unsaturated carbo

Abstract: Deoxyuridine derivatives of the formula where A is O, S or CH2; B is O, S or CHR3; R1 is H, or various substituents; R2 is H, F; R3 is H, F, OH, NH2; or R2 and R3 together form a chemical bond; D is —NHCO—, —CONH—, —O—, —C(?O)—, —CH?CH, —C?C—, —NR5—; R4 is hydrogen or various substituents; R5 is H, C1-C4 alkyl, C1-C4 alkanoyl; E is Si or C; R6, R7 and R8 are independently selected from C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, or a stable monocyclic, bicyclic or tricyclic ring system have utility in the prophylaxis o treatment of parasitic diseases such as malaria

Abstract: Peptidomimetic compounds are described which inhibit the NS3 protease of the hepatitis C virus (HCV). The compounds have the formula where the variable definitions are as provided in the specification. The compounds comprise a carbocyclic P2 unit in conjunction with a novel linkage to those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

Abstract: 4-Amino-1-((2R,3S,4S,5R)-5-azido-4-hydroxy-5-hydroxymethyl-3-methyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (22) and prodrugs thereof are hepatitis C (HCV) polymerase inhibitors. Also disclosed are compositions and methods for inhibiting HCV and treating HCV-mediated diseases, processes for making the compounds and synthetic intermediates employed in the process.

Abstract: Compounds of the formula where the variables are as defined in the specification inhibit the NS3 protease of flavivirus sych as hepatitis C virus (HCV). The compounds comprise a novel linkage between a heterocyclic P2 unit and those portions of the inhibitor more distal to the nominal cleavage site of the native substrate, which linkage reverses the orientation of peptidic bonds on the distal side relative to those proximal to the cleavage site.

Abstract: Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is —OR7, —NH—SO2R8; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl; R4 is aryl or Het; n is 3, 4, 5, or 6; R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het; R6 is C1-6alkoxy, or dimethylamino; R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R8 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 optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitro

Abstract: A topical antiviral composition comprising acyclovir, penciclovir and/or omaciclovir in a glucocorticoid-free pharmaceutical carrier comprising 15 to 25 weight % propylene glycol and 10 to 25 weight % isopropyl C12-C22 alkanoic ester. The compositions have utility in the treatment or prophylaxis of herpesvirus infections. Clinical results demonstrate that treatment commencing at the prodromal stage can prevent the development of a classic cold sore lesion in a large proportion of patients.