122 results about "Caspase inhibitors" patented technology

The present invention relates to trans-capsularly administering into a diseased joint a high specificity antagonist selected from the group consisting of: i) an inhibitor of a pro-inflammatory interleukin; ii) an inhibitor of TNF-α synthesis; iii) an inhibitor of membrane-bound TNF-α; iv) an inhibitor of a natural receptor of TNF-α; v) an inhibitor of NO synthase, vi) an inhibitor of PLA2 enzyme; vii) an anti-proliferative agent; viii) an anti-oxidant; ix) an apoptosis inhibitor selected from the group consisting of EPO mimetic peptides, EPO mimetibodies, IGF-I, IGF-II, and caspase inhibitors, and x) an inhibitor of MMPs; and xi) an inhibitor of p38 kinase.

A collection container and a method for collecting a biological sample, particularly whole blood, includes at least one stabilizing agent in an amount effective to inhibit apoptosis. The stabilizing agent comprises or consists of one or more caspase inhibitors.

Described herein are compounds that are useful as caspase inhibitors having the formula: wherein Ring A is an optionally substituted piperidine, tetrahydroquinoline or tetrahydroisoquinoline ring; R1 is hydrogen, CN, CHN2, R, or CH2Y; R is an optionally substituted group selected from an aliphatic group, an aryl group, or an aralkyl group; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; and R3 is hydrogen, an optionally substituted aryl group, an optionally substituted aralkyl group, or an optionally substituted C1-6 aliphatic group, R4 is an optionally substituted group selected from an aryl group or a heterocyclyl group, or R3 and R4 taken together with the nitrogen to which they are attached optionally form a substituted or unsubstituted monocyclic, bicyclic or tricyclic ring.

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.

Disclosed are compositions and methods for treating cancer that contain caspase inhibitors and / or antioxidant compositions. Formulations containing noncaspase inhibitor anti-cancer agents are also disclosed.

The invention relates to the discovery that the proliferation and survival of pancreatic progenitor cells can be enhanced by contacting the cells with, (1) a caspase inhibitor sufficient to reduce apoptosis in the pancreatic endocrine cells; and, (2) a growth factor in an amount sufficient to increase the level of activated Akt in the pancreatic endocrine cells.

The present invention provides methods, compositions and devices for stabilizing the extracellular nucleic acid population in a cell-containing biological sample using an apoptosis inhibitor, preferably a caspase inhibitor, a hypertonic agent and / or a compound according to formula (1) as defined in the claims.

The invention relates to processes and compounds useful for producing modified aspartic acid derivatives, such as aspartic acid aldehyde moieties. Aspartic acid derivatives are useful for preparing caspase inhibitors and / or prodrugs thereof.

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-1β secretion.

Disclosed herein is a method for making compounds that are useful as caspase inhibitor prodrugs of formula I: wherein R1 is an optionally substituted group selected from an aliphatic group, aralkyl group, heterocyclylalkyl group or aryl group, and R2 is preferably a P2—P4 moiety of a caspase inhibitor. Key intermediates include the azidolactones III and VIII:

The invention discloses an organic rare earth bacteria inhibitor, mainly, a binary or ternary compound of lanthanon and 8-Hydroxyquinoline with other organic ligand. The invention also discloses the application of the organic rare earth bacteria inhibitor in preventing the plant bacteria and pests. The plant bacteria and pests include the rice bacteria and pests, the cotton bacteria and pests, the corn bacteria and pests, the vegetable bacteria and pests, and the like. The invention widens the application range of the rare earth to the pesticide filed; secondly, the invention comprehensively takes the advantage of the bacteriostatic function of the organic ligands and the rare earth, can perform double bacteriostatic effect with high bacteriostatic effect; in addition, the dosage of the organic rare earth bacteria inhibitor is less, the toxicity is low, the effective duration is long, the medicine resistance cannot be produced, and the production cost is low.

The invention relates to the use of at least one caspase inhibitor, in particular a caspase-3 inhibitor, for preparing a pharmaceutical composition for the prophylaxis and / or therapy of a viral infection, in particular an infection with an RNA negative-strand virus, preferably an influenza infection, and to a test system for identifying suitable active substances.

The present invention provides a compound of formula I: wherein R1, R2, R3, R4, and R5 are as defined herein. The present invention also provides pharmaceutical compositions and methods using such compositions for treating a caspase-mediated diseases and processes for preparting the compounds of the invention.

The present invention relates to a pharmaceutical composition comprising a caspase inhibitor and / or a compound of the general formula R-Lys-X, methods for coating medical products using said caspase inhibitors and / or said compounds of general formula R-Lys-X and medical products coated with said caspase inhibitors and / or said compounds of general formula R-Lys-X.

This invention provides compounds of formula I:wherein Z is oxygen or sulfur; R1 is hydrogen, —CHN2, R, CH2OR, CH2SR, or —CH2Y; next to R3 represents a single or double bond; 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 is a hydrogen or C1-6 alkyl or R3 and R4 taken together form a ring; Ring A and Ring B are each heterocyclic rings, and R and R5 are as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1β secretion.

Disclosed herein is a method for making compounds that are useful as caspase inhibitor prodrugs of formula I: wherein R1 is an optionally substituted group selected from an aliphatic group, aralkyl group, heterocyclylalkyl group or aryl group, and R2 is preferably a P2-P4 moiety of a caspase inhibitor. Key intermediates include the azidolactones III and VIII:

The present invention provides a compound of formula I:wherein:X is —OR1 or —N(R5)2,Y is halo, trifluorophenoxy, or tetrafluorophenoxy;R1 is:C1-6 straight chained or branched alkyl, alkenyl, or alkynyl, wherein the alkyl, alkenyl, or alkynyl is optionally substituted with optionally substituted aryl, CF3, Cl, F, OMe, OEt, OCF3, CN, or NMe2;C1-6 cycloalkyl, wherein 1-2 carbon atoms in the cycloalkyl is optionally replaced with —O— or —NR5—;R2 is C1-6 straight chained or branched alkyl;R3 is hydrogen, halo, OCF3, CN, or CF3;R4 is hydrogen, halo, OCF3, CN, or CF3; andeach R5 is independently H, C1-6 straight chained or branched alkyl, aryl, —O—C1-6 straight chained or branched alkyl, or —O-aryl.The present invention also provides pharmaceutical compositions and methods using such compositions for treating a caspase-mediated disease, particularly in the central nervous system.

Described here are novel, highly selective inhibitors and activity based probes (ABPs) for caspases 3, 7, 8, and 9 and legumain. The compounds selectively inhibit only certain caspases. A positional scanning combinatorial library (PSCL) approach was used to screen pools of peptide acyloxymethyl ketones (AOMKs) containing both natural and non-natural amino acids for activity against a number of purified recombinant caspases. These screens were used to identify structural elements at multiple positions on the peptide scaffold that could be modulated to control inhibitor specificity towards target caspases. Further disclosed are individual optimized covalent inhibitors that could also be equipped with various tags for use as activity based probes, as well as labeled substrates.

This invention provides caspase inhibitors having the formula:wherein R1 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R2 and R3 are each independently selected from hydrogen or an optionally substituted C1–C6 aliphatic group; and R4 and R5 are each independently selected from hydrogen, an optionally substituted C1–C6 aliphatic group, or R4 and R5 taken together with the ring to which they are attached form an optionally substituted bicyclic ring. The caspase inhibitors are useful for treating a number of diseases such as cancer, acute inflammatory and autoimmune disorders, ischemic diseases and certain neurodegenerative disorders.

Provided are to a freezing medium composition for cryopreserving amniotic fluid-derived stem cells, which has A lower concentration of Me2SO and eliminates fetal bovine serum and at the same time does not induce cryoinjury to fluid-derived stem cells and makes it possible to cryopreserve fluid-derived stem cells for a prolonged time using trehalose, sucrose and catalase, and a method for cryopreserving the same. According to the present invention, AFSCs can be cryopreserved with 1 / 4 the standard Me2SO concentration with the addition of disaccharides, antioxidants and caspase inhibitors. As a result, the use of Me2SO at low concentrations in cell freezing solutions may support the development of clinical trials of AFSCs.

The invention relates to novel diazoketone derivatives. The invention also relates to processes for homologation of these diazoketone derivatives. The processes are useful for preparing compounds that are caspase inhibitors.

The present invention provides a compound of formula I:wherein:X is —OR1 or —N(R5)2,Y is halo, trifluorophenoxy, or tetrafluorophenoxy;R1 is:C1-6 straight chained or branched alkyl, alkenyl, or alkynyl, wherein the alkyl, alkenyl, or alkynyl is optionally substituted with optionally substituted aryl, CF3, CI, F, OMe, OEt, OCF3, CN, or NMe2;C1-6 cycloalkyl, wherein 1-2 carbon atoms in the cycloalkyl is optionally replaced with —O— or —NR5—;R2 is C1-6 straight chained or branched alkyl;Art Unit 1625R3 is hydrogen, halo, OCF3, CN, or CF3;R4 is hydrogen, halo, OCF3, CN, or CF3; andeach R5 is independently H, C1-6 straight chained or branched alkyl, aryl, —O—C1-6 straight chained or branched alkyl, or —O-aryl. The present invention also provides pharmaceutical compositions and methods using such compositions for treating a caspase-mediated disease, particularly in the central nervous system.

The present invention relates to novel classes of compounds of formula I which are caspase and TNF-alpha inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase and TNF-alpha activity and consequently, can be advantageously used as agents against caspase-, interleukin-1-(“IL-1”), apoptosis-, interferon-γ inducing factor-(IGIF), interferon-γ-(“IFN-γ”), or TNF-alpha mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to processes for preparing the compounds of this invention. This invention also relates to methods for inhibiting caspase and TNF-alpha activity and decreasing IGIF production and IFN-γ production and methods for treating caspase-, interleukin-1, apoptosis-, and interferon-γ-, and TNF-alpha mediated diseases using the compounds and compositions of this invention.

The present invention provides a compound of formula I:wherein R1, R2, R3, R4, and R5 are as defined herein. The present invention also provides pharmaceutical compositions and methods using such compositions for treating a caspase-mediated diseases and processes for preparing the compounds of the invention.

The present invention relates to trans-capsularly administering into a diseased joint a high specificity antagonist selected from the group consisting of:i) an inhibitor of a pro-inflammatory interleukin;ii) an inhibitor of TNF-α synthesis;iii) an inhibitor of membrane-bound TNF-α;iv) an inhibitor of a natural receptor of TNF-α;v) an inhibitor of NO synthase,vi) an inhibitor of PLA2 enzyme;vii) an anti-proliferative agent;viii) an anti-oxidant;ix) an apoptosis inhibitor selected from the group consisting of EPO mimetic peptides, EPO mimetibodies, IGF-I, IGF-II, and caspase inhibitors, andx) an inhibitor of MMPs; andxi) an inhibitor of p38 kinase.

The invention relates to a new combination of an anti-MAdCAM antibody with an anti-fibrotic agent, such as a protease inhibitor, preferably a caspase inhibitor. The invention also relates to pharmaceutical compositions comprising the combination of the invention, and the use of the combination for the treatment of liver fibrosis.

This invention provides novel caspase inhibitors useful for prophylaxis or treatment of a number of pathologies, including, for example, Huntington's disease. In certain embodiments the inhibitors include inhibitors of casepase-3 and / or casepase-6.