Abstract: The present invention provides hydroxamate compounds which are deacetylase inhibitors. The compounds are suitable for pharmaceutical compositions having anti-proliferative properties.

Abstract: The present invention relates to a method for the treatment of cancer in a patient in need thereof. The method comprises administering to a patient in need thereof a first amount of a histone deacetylase inhibitor in a first treatment procedure, and a second amount or dose of radiation in a second treatment procedure. The first and second treatments together comprise a therapeutically effective amount. The combination of the HDAC inhibitor and radiation therapy is therapeutically synergistic.

Abstract: A drug for external application to the skin, for inhibiting sebum secretion, comprising a matrix metalloproteinase inhibitor.

Abstract: This invention is directed to aromatic sulfone hydroxamates (also known as “aromatic sulfone hydroxamic acids”) and salts thereof that, inter alia, inhibit matrix metalloproteinase (also known as “matrix metalloprotease” or “MMP”) activity and/or aggrecanase activity. This invention also is directed to a prevention or treatment method that comprises administering such a compound or salt in an MMP-inhibiting and/or aggrecanase-inhibiting effective amount to an animal, particularly a mammal having (or disposed to having) a pathological condition associated with MMP and/or aggrecanase activity.

Abstract: The present invention provides epitopes present on cancer cells and important in physiological phenomena such as cell rolling, metastasis, and inflammation. Therapeutic and diagnostic methods and compositions using antibodies capable of binding to the epitopes are provided. Methods and compositions according to the present invention can be used in diagnosis of and therapy for such diseases as cancer, including tumor growth and metastasis, leukemia, auto-immune disease, and inflammatory disease.

Abstract: The present invention provides the compound having the formula: 1

Abstract: The present invention relates to the use of creatine compounds including cyclocreatine and creatine phosphate for treating or preventing a metabolic disorder consisting of hyperglycemia, insulin dependent diabetes mellitus, impaired glucose tolerance, hyperinsulinemia, insulin insensitivity, diabetes related diseases in a patient experiencing said disorder. The creatine compounds which can be used in the present method include (1) analogues of creatine which can act as substrates or substrate analogues for the enzyme creatine kinase; (2) compounds which can act as activators or inhibitors of creatine kinase; (3) compounds which can modulate the creatine transporter (4) N-phosphocreatine analogues bearing transferable or non-transferable moieties which mimic the N-phosphoryl group. (5) compounds which modify the association of creatine kinase with other cellular components.

Abstract: Compounds having a metalloproteinase inhibitory activity, represented by the formula (I), its optically active isomers, their pharmaceutically acceptable salts, or hydrates thereof.

Abstract: An isolated nucleic acid containing a human ribonucleotide reductase M2 subunit promoter sequence or genomic sequence. Also disclosed are methods of determining whether a subject is suffering from or at risk for developing a cell proliferation-associated disorder, identifying a compound for treating a cell proliferation-associated disorder, treating a cell proliferation-associated disorder, and developing a procedure for treating a cell proliferation-associated disorder.

Abstract: Disclosed are compounds which are inhibitors of metalloproteases and which are effective in treating conditions characterized by excess activity of these enzymes.

Abstract: This invention relates to a method of treating inflammatory diseases in a mammal comprising administering to the mammal a therapeutically effective amount of a combination of: (i) at least one TACE inhibitor of Formula (I), (II), (III), or (IV) of the present invention or a stereoisomer or pharmaceutically acceptable salt form thereof, (ii) one or more anti-inflammatory agents selected from the group consisting of: selective COX-2 inhibitors, interleukin-1 antagonists, dihydroorotate synthase inhibitors, p38 MAP kinase inhibitors, TNF-&agr; inhibitors, TNF-&agr; sequestration agents, and methotrexate. The invention also relates to compositions and kits containing the same.

Abstract: Spray dried solid dispersions comprising a sparingly soluble drug and hydroxypropylmethylcellulose acetate succinate (HPMCAS) provide increased aqueous solubility and/or biavailability in a use environment.

Abstract: Described is a protective solution for avoiding ischemic, storage or ischemia/reperfusion to organs, or to isolated cell systems, or to tissue components after perfusion, surgery, transplantation, or cryopreservation and subsequent reperfusion, which contains alkali ions, and if need be also alkaline earth ions as the electrolyte, a buffer e.g. on a histidine derivation basis, as well as a polyol and/or a saccharide, has an osmolarity of about 290 mosm/l to about 350 mosm/l, as well as a pH value of about 6.8 to about 7.4, and to which hydroxamic acid, and/or one or more hydroxamic acid derivatives are added.

Abstract: This invention relates to certain sulfonamide derivatives that are inhibitors of procollagen C-proteinase, pharmaceutical compositions containing them, methods for their use and methods for preparing these compounds.

Abstract: Compounds of formula (I): in which: Ar represents an aromatic or a heteroaromatic radical optionally substituted, in particular, with an alkyl or a carboxyl group, R2 and R3 represent, in particular, H or alkyl, or R2 and R3, taken together, form a 5- or 6-membered ring, R4 and R5 represent, in particular, H or halogen, R6 represents, in particular, H or lower alkyl, and the salts of the compounds of formula (I). These compounds can be used in particular in the treatment of dermatological complaints associated with a keratinization disorder, and for combating ageing of the skin.

Abstract: The present application describes novel &bgr;-sulfone derivatives of formula I: 1

Abstract: The present invention relates to thiourea compounds and the pharmaceutical compositions containing the same, and particularly, to novel thiourea compounds as an antagonist against vanilloid receptor (VR) and the pharmaceutical compositions thereof. As diseases associated with the activity of vanilloid receptor, pain, acute pain, chronic pain, neuropathic pain, post-operative pain, migraine, arthralgia, neuropathies, nerve injury, diabetic neuropathy, neurodegeneration, neurotic skin disorder, stroke, urinary bladder hypersensitiveness, irritable bowel syndrome, a respiratory disorder such as asthma or chronic obstructive pulmonary disease, irritation of skin, eye or mucous membrane, fervescence, stomach-duodenal ulcer, inflammatory bowel disease and inflammatory diseases can be enumerated. The present invention provides a pharmaceutical composition for prevention or treatment of these diseases.

Abstract: Compounds of the formula: 1

Abstract: Compounds of formula (I): wherein X1 is alkyl, sulphonyl or carboxy: X2 is hydrogen or alkyl; R1 is arylmethyl or heterocyclylmethyl; R2 is alkyl, alkenyl, aryl, cycloalkyl or cycloalkenyl; and R3 is hydrogen, alkyl, alkenyl, alkynyl or aryl; are useful in the treatment of disorders mediated by s-CD23.

Abstract: Compounds of formula (I) wherein R is hydrogen, alkyl alkenyl, alkynyl, aryl, heteroaryl or heterocyclyl; and R1 is bicyclyl or heterobicyclyl; are useful in the treatment and prophylaxis of conditions mediated by s-CD23 or TNF.

Abstract: Methods, compounds, and formulations are provided to reduce pigmentation in mammalian skin, comprising hydroxamic acid and its derivatives, and especially benzohydroxamic acid and its derivatives. The compounds preferably inhibit pigment synthesis in melanocytes through inhibition of melanocyte tyrosinase. The methods can be used for lightening skin, and for treating uneven skin complexions, which result from hyperpigmentation-related medical conditions such as melasma, age spots, freckles, ochronosis, and lentigo. The compounds can be used medically or cosmetically, and preferably as topical formulations.

Abstract: Formula (I) compounds are described, where the groups are defined in the description, as well as processes for their preparation and their use as medicaments, particularly as selective phosphodiesterase IV inhibitors.

Abstract: Compositions comprising collagen and at least one metalloprotease inhibitor, and methods of making and using same are provided.

Abstract: The present invention provides compounds that are inducers or inhibitors of apoptosis or apoptosis preceded by cell-cycle arrest. In addition, the present invention provides pharmaceutical compositions and methods for treating mammals with leukemia or other forms of cancer or for treating disease conditions caused by apoptosis of cells.

Abstract: The present invention relates to a novel sulfonic acid derivative of hydroxamic acid or a pharmacologically acceptable salt thereof. More particularly, the present invention relates to a sulfonic acid derivative of hydroxamic acid or a pharmacologically acceptable salt thereof, which is useful as an inhibitor of lipopolysaccharides (LPS). In addition, the present invention relates to a novel intermediate compound useful for the synthesis of this sulfonic acid derivative of hydroxamic acid.

Abstract: The present invention provides a compound of formula (1), or pharmaceutical acceptable salts thereof wherein R1 is C4-12 alkyl, C4-12 alkenyl, C4-12 alkynyl, —(CH2)h-C3-8 cycloalkyl, substituted and unsubstituted —(CH2)h-aryl, substituted and unsubstituted-(CH2)h-het, R2 is substituted and unsubstituted C1-12 alkyl, substituted and unsubstituted C2-12 alkenyl, substituted and unsubstituted C2-12 alkynyl, substituted and unsubstituted-(CH2)h-C3-8 cycloakyl, substituted and unsubstituted —(CH2)h-C3-8 unsubstituted-(CH2)h-C3-8 cycloakyl, substituted and unsubstituted —(CH2)h-C3-8 cycloalkenyl, substituted and unsubstituted-(CH2)h-aryl, substituted and unsubstituted-(CH2)h-heterocyclic ring, substituted and unsubstituted —(CH2)i-X—R4 (X is —O—, —S(═O)j-, —NR7-, —S(═O)2NR8-, or —C(═O)—), and —(CH2)iCHR5R6.

Abstract: Novel active compound combinations of compounds of the formula (I) 1

Abstract: The present invention relates to a hydroxamic acid derivative of the formula (I) wherein each symbol is as defined in the specification, a pharmacologically acceptable salt thereof, a pharmaceutical composition containing the derivative or a salt thereof, and to pharmaceutical use thereof. The hydroxamic acid derivative and a pharmacologically acceptable salt thereof of the present invention have an inhibitory activity of TNF &agr; production, and are useful for, for example, the prophylaxis and treatment of the diseases such as autoimmune diseases and inflammatory diseases (e.g., sepsis, MOF, rheumatoid arthritis, Crohn's disease, cachexia, myasthenia gravis, systemic lupus erythematosus, asthma, I type diabetes, psoriasis and the like), and the like.

Abstract: Phenylalanine derivatives of the following formula and analogues thereof have an antagonistic activity to &agr;4&bgr;7 integrin and a selectivity toward &agr;4&bgr;1 integrin. They are used as therapeutic agents for various diseases to which &agr;4&bgr;7 integrin relates.

Abstract: The invention provides a use of a metalloproteinase inhibitor for the preparation of a pharmaceutical composition for treating human pulmonary emphysema which comprises admixing the metalloproteinase inhibitor in an amount effective to treat human pulmonary emphysema and a pharmaceutically acceptable carrier. This invention also provides a pharmaceutical composition which comprises a metalloproteinase inhibitor in an amount effective to treat human pulmonary emphysema and a pharmaceutically acceptable carrier.

Abstract: Novel cyclo azaphospha hydrocarbons according to formula I are provided. The compounds are useful as metalloprotease inhibitors.

Abstract: The present invention relates to certain tri-substituted phenyl derivatives and analogues of formula (I), to a process for preparing such compounds, having the utility in clinical conditions associated with insulin resistance, to methods for their therapeutic use and to pharmaceutical compositions containing them.

Abstract: The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.

Abstract: This invention pertains to the discovery that inhibitors of matrix metalloproteinases (e.g. MMP-9) can reduce neurological damage (e.g. secondary damage) following trauma to nervous tissue in a mammal, and/or reduce abnormal vascular permeability associated with spinal cord injury, and/or improving recovery of neurological function following injury to neurological tissue. Methods of use of matrix metalloproteinase inhibitors for such applications are provided.

Abstract: Compounds having a metalloproteinase inhibitory activity, represented by the formula (I), its optically active isomers, their pharmaceutically acceptable salts, or hydrates thereof.

Abstract: The present application describes novel cyclic hydroxamic acids of formula I: 1

Abstract: Compounds of formula (I) wherein R is hydrogen, alkyl, alkenyl, alkynyl, aryl, heteroaryl or heterocyclyl; R1 is bicyclyl or heterobicyclyl; R2 is aryl, heteroaryl, heterocyclyl, alkoxy, alkyl, hydroxy or optionally substituted amino and n is from 0 to 3; with the provisos than when n is 0 R2 is alkyl or when n is from 1 to 3 R2 is not alkyl, are useful in the treatment and prophylaxis of conditions mediated by CD23 or TNF.

Abstract: An antibody of the invention interacts with human DR5 or with human DR4 to produce agonistic or antagonistic effects downstream of the receptor including inhibition of cell proliferation and apoptosis. Methods and uses for the antibodies, optionally in combination with various therapeutic agents, are detailed, including treatment of apoptosis-related disease and treatment of dysregulated cell growth.

Abstract: Compounds of the formula 1

Abstract: This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating disorders mediated by cyclooxygenase-2 or 5-lipoxygenase, such as inflammation.

Abstract: A method of treating an autoimmune disease comprising administering to the subject a treatment effective amount of a histone hyperacetylating agent, or a pharmaceutically acceptable salt thereof.

Abstract: A treatment and/or prevention agent for osteoarthritis comprising N-hydroxy-5-ethoxymethyloxy-2(S)-methyl-4(S)-(4-phenoxybenzoyl)amino pentanamide having an inhibitory activity of matrix metalloproteinases, or a non-toxic salt thereof as active ingredient.

Abstract: The present invention concerns the generation of hydroxamic acid thrombospondin-peptide analogs that inhibit aggrecanase activity. These analogs are useful in the treatment of diseases characterized by cartilage degradation, such as osteoarthritis, rheumatoid arthritis spondylarthropathies, and septic arthritis. The invention describes a novel small molecule, enzyme inhibitor that binds both the enzyme and its naturally occurring substrate.

Abstract: This invention pertains to a method for treating a human with human immunodeficiency virus infection which comprises administering to the human a therapeutically effective amount of a thymidine analog, which analog acts as an inhibitor of viral reverse transcriptase necessary for viral replication of human immunodeficiency virus, and a thymidylate synthase inhibitor, or pharmaceutically acceptable salts thereof.

Abstract: Tetrahydrofurans, tetrahydrothiophenes, pyrrolidines and cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. It has been determined that 5-lipoxygenase activity, oral availability, and stability in vivo (for example, glucuronidation rate) can vary significantly among the optical isomers of the disclosed compounds.

Abstract: The invention relates to the modulation of gene expression. In particular, the invention relates to compositions comprising antisense oligonucleotides which inhibit expression of a gene in operable association with protein effectors of a product of that gene, and methods of using the same.

Abstract: Hydroxamic and carboxylic acid derivatives having MMP and TNF inhibitory activity.

Abstract: In one aspect, pharmaceutical compositions comprising dispersions of an acid-sensitive drug and a neutral dispersion polymer are disclosed. The acid-sensitive drug has improved chemical stability relative to dispersions of the drug and acidic polymers. In another aspect, pharmaceutical compositions of low-solubility drugs and amphiphilic, hydroxy-functional vinyl copolymers are disclosed.

Abstract: Dapsone and related sulfones are known to have therapeutic activity against leprosy, dermatitis herpetiformis, actinomycotic mycetoma, asthma, malaria, rheumatoid arthritis, Kaposiís sarcoma, pneumocystis carinií (pneumonia), subcorneal pustular dermatosis and cystic acne, in patients in need of such therapy. These sulfones are also known to have therapeutic activity against memory loss in patients in need of such therapy, including patients suffering from Alzheimer's disease and related neurodegenerative disorders. It has now been found that new, modified-release formulations of dapsone and related sulfones may also be used that decrease side effects and increase effectiveness of the drugs. New methods are disclosed utilizing certain formulations of dapsone and related sulfones that improve the therapeutic index of said drugs.

Abstract: A compound of the formula (I): R1—CO—N(OH)—CR2R3—CR4R5—CONH—CR6R7—CONR8R9  (I) wherein: R1 is C1-6alkyl, aryl or arylC1-6alkyl; R2 is hydrogen, C1-6alkyl, C3-8cycloalkyl, aryl or arylC1-6alkyl; R3 is hydrogen, C1-6alkyl or arylC1-6alkyl; or R2 and R3, together with the carbon atom to which they are joined, form a C3-8cycloalkyl ring; R4 is benzyl, phenethyl, phenylpropyl, phenylbutyl or flurophenylbutyl; R5 is hydrogen, C1-6alkyl or arylC1-6alkyl; R6 is hydrogen, C1-6alkyl, C2-6alkenyl, C3-8cycloalkylC1-6alkyl, arylC1-6alkyl, heteroarylC1-6alkyl or the side-chain of a naturally occurring amino acid; R7 is hydrogen or C1-6alkyl; R8 is hydrogen, C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkenyl, arylC1-6alkyl, heteroarylC1-6alkyl or heterocyclylC1-6alkyl; R9 is hydrogen or C1-6alkyl; or R8 and R9, together with the nitrogen atom to which they are joined, form a heterocyclic ring; wherein any group or ring in R1-R9 is optionally substituted; or a pharma