Abstract: The present invention relates to compounds of formula I or formula Ia or pharmaceutically acceptable salts thereof, that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3–NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are useful as antiviral agents. The invention further relates to pharmaceutically acceptable compositions comprising said compounds either for ex vivo use or for administration to a patient suffering from HCV infection and processes for preparing the compounds. The invention also relates to methods of treating an HCV infection in a patient by administering a pharmaceutical composition comprising a compound of this invention.

Abstract: The present invention relates to acyclic and cyclic amine derivatives for treating or preventing neuronal damage associated with neurological diseases. The invention also provides compositions comprising the compounds of the present invention and methods of utilizing those compositions for treating or preventing neuronal damage.

Abstract: This invention describes novel pyrazole compounds of formula III: wherein Ring D is a 5–7 membered monocyclic ring or 8–10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5–8 membered carbocyclo ring; and R2 and R2? are as described in the specification. The compounds are useful as protein kinase inhibitors, especially as inhibitors of aurora-2 and GSK-3, for treating diseases such as cancer, diabetes and Alzheimer's disease.

Abstract: The present invention relates to compounds useful of inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

Abstract: This invention describes novel pyrazole compounds of formula IV: wherein Z1 or Z2 is nitrogen, Q is —S—, —O—, —N(R4)—, —C(R6?)2—, 1,2-cyclopropanediyl, 1,2-cyclobutanediyl, or 1,3-cyclobutanediyl, and R1 is T-Ring D, wherein Ring D is a 5–7 membered monocyclic ring or 8–10 membered bicyclic ring selected from aryl, heteroaryl, heterocyclyl or carbocyclyl; Rx and Ry are independently selected from T—R3 or L—Z—R3, or Rx and Ry are taken together with their intervening atoms to form a fused, unsaturated or partially unsaturated, 5–7 membered ring having 0–3 heteroatoms; and R2 and R2? are as described in the specification. The compounds are useful as protein kinase inhibitors, especially as inhibitors of Aurora-2 and GSK-3, for treating diseases such as cancer, diabetes and Alzheimer's disease.

Abstract: The present invention relates to compounds which inhibit IMPDH. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting IMPDH enzyme activity and consequently, may be advantageously used as therapeutic agents for IMPDH-mediated processes. This invention also relates to methods for inhibiting the activity of IMPDH using the compounds of this invention and related compounds.

Abstract: The present invention provides compounds of formula I: or a pharmaceutically acceptable derivative o thereof, wherein A, B, Ra, R1, R2, R3, and R4 are as described in the specification. These compounds are inhibitors of protein kinase, particularly inhibitors of JNK, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli; Lck and Src kinase. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Abstract: The present invention relates to compounds useful as inhibitors of CAK, compositions thereof. The present invention also relates to methods using the compositions for treating CAK-mediated diseases, such as fungal infections.

Abstract: This invention provides caspase inhibitors of formula I: wherein Z is oxygen or sulfur; R1is hydrogen, —CHN2, R, CH2OR, CH2SR, or —CH2Y; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R3 is a group capable of fitting into the S2 subsite of a caspase enzyme; R4 and R5 are taken together with the intervening nitrogen to form heterocyclic ring and R is as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1? secretion.

Abstract: Described herein are compounds that are useful as protein kinase inhibitors having the formula: where R1-4, Q, and T are described in the specification. The compounds are useful for treating disease states in mammals that are alleviated by a protein kinase inhibitor, particularly diseases such as cancer, inflammatory disorders, restenosis, and cardiovascular disease.

Abstract: This invention provides caspase inhibitors having the formula: wherein Ring A is an optionally substituted piperidine, tetrahydroquinoline or tetrahydroisoquinoline ring; R1 is hydrogen, CHN2, R, or —CH2Y; R is an optionally substituted group selected from an aliphatic group, an aryl group, an aralkyl group, a heterocyclic group, or an heterocyclylalkyl group; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; Ar is an optionally substituted aryl group; and R3 is hydrogen, an optionally substituted C1-6 alkyl, F2, CN, aryl or R3 is attached to Ar to form an unsaturated or partially saturated five or six membered fused ring having 0–2 heteroatoms. The compounds are useful for treating caspase-mediated diseases in mammals.

Abstract: The present invention provides compounds of formula I: or a pharmaceutically acceptable derivative thereof, wherein R1, R2, V1, V2, and V3 are as described in the specification. These compounds are inhibitors of protein kinase, particularly inhibitors of AKT, PKA, PDK1, p70S6K, or ROCK kinase, mammalian protein kinases involved in proliferative and neurodegenerative disorders. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of utilizing those compositions in the treatment of various disorders.

Abstract: This invention provides a method of treating a disease state in mammals that is alleviated by treatment with a protein kinase inhibitor, especially an ERK inhibitor, which method comprises administering a compound having the pharmacophoric features Grp 1, Grp 2 and Grp 3: Grp 1 is an optionally substituted aryl or aliphatic group; Grp 2 is a heteroaromatic ring having one to three nitrogens, said ring comprising a hydrogen bond acceptor HBA2 optionally bonded to a hydrogen bond donor HBD2, and Grp 3 is a heteroaromatic ring comprising a hydrogen bond donor HBD1, with distances between the pharmacophoric features defined in the specification. The method is useful for treating cancer, stroke, diabetes, hepatomegaly, cardiovascular disease, Alzheimer's disease, cystic fibrosis, viral disease, autoimmune diseases, atherosclerosis, restenosis, psoriasis, allergic reactions, inflammation, neurological disorders or a hormone-related disease.

Abstract: Described herein are compounds that are useful as protein kinase inhibitors having the formula: where R1, R2, T and Ht are described in the specification. The compounds are useful for treating disease states in mammals that are alleviated by a protein kinase inhibitor, particularly diseases such as cancer, inflammatory disorders, restenosis, and cardiovascular disease.

Abstract: A compound having the formula (I): wherein: each R1, R2, R3 and R4 are independently selected from (C1-C10)-straight or branched alkyl, Ar-substituted- (C1-C10)-straight or branched alkyl, (C2-C10)-straight or branched alkenyl or alkynyl, or Ar-substituted-(C2-C10)-straight or branched alkenyl or alkynyl; wherein one to two CH2 groups of said alkyl, alkenyl, or alkynyl chains in each of R1, R2, R3 and R4 are optionally and independently replaced with O, S, S(O), S(O), S(O)2, C(O) or N(R5) in a chemically stable arrangement, wherein the CH2 group of R1 and R2 bound directly to said nitrogen cannot be replaced with C(O); or R1 and R2 taken together form a 4 to 7 membered ring; or R3 and R4 taken together form a 3 to 7 membered ring; wherein a CH2 in either the R1 and R2 ring system or the R3 and R4 ring system is independently and optionally replaced with O, C(O), N(R5), S, S(O), S(O)2 in a chemically stable arrangement; or wherein either or both of the R1 and R2 ring system and the R3 and R4 ring sy

Abstract: The present invention provide a compound of formula I or II: or a pharmaceutically acceptable derivative thereof, wherein R1, R2, R3, and R4 are as described in the specification. These compounds are inhibitors of protein kinase, particularly inhibitors of JNK, a mammalian protein kinase involved cell proliferation, cell death and response to extracellular stimuli; and Src-family kinases, especially Src and Lck kinases. These compounds are also inhibitors of GSK3 and CDK2 kinases. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Abstract: The present invention relates to compounds of the formula I: where Ring A is a thiazole, oxazole, imidazole or pyrazole and the substituents are as described in the specification, and pharmaceutically acceptable salts thereof. The compounds inhibit bacterial gyrase activity and therefore are useful for treating bacterial infections in mammals.

Abstract: The present invention relates to peptidomimetic compounds which inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The compounds of this invention have a bridged bicyclic moiety at the P2 position. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention.

Abstract: The present invention provides compounds of formula I: wherein A is N or CR, and G, R1, R2 and R3 are as described in the specification. These compounds are inhibitors of protein kinase, particularly inhibitors of Src mammalian protein kinase involved in cell proliferation, cell death and response to extracellular stimuli. The invention also relates to methods for producing these inhibitors. The invention also provides pharmaceutical compositions comprising the inhibitors of the invention and methods of utilizing those compositions in the treatment and prevention of various disorders.

Abstract: This invention provides a method of treating a disease state in mammals that is alleviated by treatment with a protein kinase inhibitor, especially an ERK inhibitor, which method comprises administering a compound having the pharmacophoric features Grp1, Grp2 and Grp3: Grp 1 is an optionally substituted aryl or aliphatic group; Grp 2 is a heteroaromatic ring having one to three nitrogens, said ring comprising a hydrogen bond acceptor HBA2 optionally bonded to a hydrogen bond donor HBD2, and Grp3 is a heteroaromatic ring comprising a hydrogen bond donor HBD1, with distances between the pharmacophoric features defined in the specification. The method is useful for treating cancer, stroke, diabetes, hepatomegaly, cardiovascular disease, Alzheimer's disease, cystic fibrosis, viral disease, autoimmune diseases, atherosclerosis, restenosis, psoriasis, allergic reactions, inflammation, neurological disorders or a hormone-related disease.