Abstract: The present invention is directed to compounds of formula (I), or a pharmaceutically suitable salt or prodrug thereof, which are useful for the selective inhibition of protein tyrosine phosphatase-1B (PTP1B), and are useful for the treatment of disorders caused by overexpressed or altered protein tyrosine phosphatase 1B.

Abstract: The present invention provides a method for the prophylactic and therapeutic treatment of cancer. The method comprises administering to an animal, preferably a mammal, more preferably a human, at risk for developing a cancer or having a cancer a nitroxide or a prodrug thereof, wherein the nitroxide or prodrug thereof preferably is alicyclic or heterocyclic and more preferably is a compound of Formula (I) or Formula (II): in an amount sufficient to prevent or treat said cancer, wherein said cancer is susceptible to prevention or treatment by said nitroxide or prodrug thereof.

Abstract: This invention relates to a series of substitituted amino acids of Formula I pharmaceutical compositions containing them and intermediates used in their manufacture. The compounds of the invention are small molecules which bind to the erythropoietin receptor and compete with the natural ligand for binding to this receptor.

Abstract: Substituted heterocyclinc compounds are disclosed. The compounds are useful for treating multidrug resistance. The compounds can be formulated in compositions with a carrier and, optionally, a therapeutic agent.

Abstract: The present invention relates to compounds which comprise a nitrogen-containing ring scaffold substituted by an R1 alkyl units selected from the group consisting of C1–C12 linear or branched alkyl, C3–C8 cyclic alkyl, C2–C12 linear or branched alkenyl, or haloalkyl, for example, the 2-keto-3-alkylpiperazines having the formula: wherein R is selected from the group consisting of phenyl, 3-fluorophenyl, 4-fluorophenyl, 3,5-difluorophenyl, and 4-chlorophenyl; R1 is selected from the group consisting of methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, sec-butyl, tert-butyl, cyclopropyl, cyclopropylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cyclohexylmethyl, benzyl, allyl, 1-methylallyl, 2-methylallyl, but-2-enyl, and propargyll; R7a is selected from the group consisting of hydrogen, —CO2H, —CONH2, —CONHCH3, and —CON(CH3)2; R8 is benzyl, substituted benzyl, or naphthalen-2-ylmethyl.

Abstract: The present invention relates to () non-peptide aspartyl protease inhibitors; (ii) methods for modulating the processing of an amyloid precursor protein (APP); (iii) methods for modulating the processing of a tau protein (?-protein); and (iv) methods for treating neurodegenerative diseases.

Abstract: The present invention provides compounds, compositions and methods for the selective inhibition of cathepsin S. In a preferred aspect, cathepsin S is selectively inhibited in the presence of at least one other cathepsin isozyme (e.g., cathespin K). The present invention also provides methods for treating a disease state in a subject by selectively inhibiting cathepsin S.

Abstract: The present invention relates to compounds, methods and pharmaceutical compositions for stimulating the growth of neurites in nerve cells. The compounds and the compositions and methods that utilize them can be used, either alone or in conjunction with a neurotrophic factor, such as nerve growth factor, to promote repair of neuronal damage caused by disease or physical trauma.

Abstract: A compound having the general formula (I): wherein: X is N or C; R0 is H, a lower alkyl group, a lower O-alkyl group, lower alkyl group, a benzyl group, a phenyl group, a heterocyclic amine group, a cycloalkyl group, a cycloalkyl group substituted with O-alkyl or, a furyl group; R1 and R2 are, independently, H, an amine group, a lower alkyl group, a lower O-alkyl group, a lower S-alkyl group or a lower N-alkyl group, or R1 and R2 taken together with the carbon atoms to which they are attached form a five-membered carbocyclic or heterocyclic ring, where the heteroatoms of the heterocyclic ring are one or two oxygen atoms, and/or where any substituent on said carbocyclic or heterocyclic ring is chosen from O, S and N; n is 0,1,2,3 or 4; m is 0 or 1; and pharmaceutically acceptable salts thereof; with the proviso that said compound is not 1-[(4-methoxyphenyl)sulfonyl]piperazine or 1-(1,3-benzodioxol-5-ylsulfonyl)piperazine.

Abstract: There is provided compounds of formula I, wherein R1, R2, R3, Y, n and B have meanings given in the description which are useful as competitive inhibitors of trypsin-like proteases, such as thrombin, and in particular in the treatment of conditions where inhibition of thrombin is required (e.g. thrombosis) or as anticoagulants.

Abstract: Compounds of the formula and their salts, wherein Cy represents cyclohexyl; Y is CH?CH?, CH?2, ? or Cy, X is trivalent straight-chain alkylene (3–10C) or trivalent straight-chain 1-alkenylene (3–10C) optionally substituted by oxo at the C adjacent N when n is 0 and Y is ?2CH; and is otherwise trivalent straight-chain alkylene (5–10C) or trivalent straight-chain 1-alkenylene (5–10C) optionally substituted by oxo at the C adjacent N; Z is N, NCO, CHNCOR1 or CHNR1, wherein R1 is alkyl (1–6C); and n is 0–5; wherein each ? and Cy independently may optionally be substituted by alkyl (1–6C) or by halo, CF3, OCF3, NO2, NR2, OR, SR, COR, COOR, CONR2, NROCR or OOCR where R is H or alkyl (1–4C), or two substituents may form a 5–7 membered ring with the proviso that the compounds of formula (1) contain at least one aromatic moiety, are useful as calcium channel blockers.

Abstract: A NF-?B inhibitor represented by the following formula (I) is provided: ?

Abstract: This invention relates to methods of using neurotrophic compounds having an affinity for FKBP-type immunophilins to stimulate or promote neuronal growth or regeneration and to prevent neuronal degeneration.

Abstract: A cell adhesion inhibitor of the general formula: R3-L-L?-R1 is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. Also disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compositions containing the same.

Abstract: Compounds having the formula are apoptosis promoters. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

Abstract: Epothilone derivatives are co-administered with an antidiarrheal agent, e.g., a DPP-IV inhibitor, in the treatment of a proliferative disease.

Abstract: (R)-Enantiomers of quaternary ammonium salts of general formula (I) are described: where R, R1, R2, R3, X and Z are as defined in the description. The process for their preparation and pharmaceutical preparations thereof are also described. The quaternary salts of the invention are useful in the inhibition of chemotaxis of neutrophils and monocytes induced by the fraction C5a of the complement and are used in the treatment of psoriasis, pemphigus and pemphigoid, rheumatoid arthritis, intestinal chronic inflammatory pathologies including ulcerative colitis, acute respiratory distress syndrome, idiopathic fibrosis, cystic fibrosis, chronic obstructive pulmonary disease and glomerulonephritis. The compounds of the invention are advantageously used in the prevention and the treatment of injury caused by ischemia and reperfusion.

Abstract: The present invention relates to a novel combination of a soft steroid, in particular loteprednol, and at least one antihistamine, such as, for example, azelastine and/or levocabastine, for simultaneous, sequential or separate administration in the local treatment of allergies and airway disorders, for example of allergic rhinitis (rhinoconjunctivitis).

Abstract: Novel PDF inhibitors and novel methods for their use are provided.

Abstract: Certain novel 4-substituted N-acylated piperidine derivatives are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the activation of MC-4R, such as obesity, diabetes, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.

Abstract: Certain novel 4-substituted N-acylated piperidine derivatives are agonists of the human melanocortin receptor(s) and, in particular, are selective agonists of the human melanocortin-4 receptor (MC-4R). They are therefore useful for the treatment, control, or prevention of diseases and disorders responsive to the activation of MC-4R, such as obesity, diabetes, sexual dysfunction, including erectile dysfunction and female sexual dysfunction.

Abstract: The subject invention encompasses compounds of the formula: wherein R1, R2, and R3 are as defined herein. The subject invention also concerns methods for synthesizing the compounds of the invention. The invention also concerns compositions comprising the above compounds as well as methods for treating pain in a patient, where the method comprises administering a compound of the invention to a patient in need of such treatment.

Abstract: A method for the treatment of bacterial infections in humans and non-human mammals, which comprises inhibiting bacterial growth by administering to a subject an antibacterially effective dose of a compound of formula (I) or a pharmaceutically or veterinarily acceptable salt thereof:

Abstract: Selected substituted piperidine compounds are effective for prophylaxis and treatment of diseases, such as obesity and the like. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving activation of the melanocortin receptor. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract: Provided herein are novel and useful compounds having a tryptase inhibition activity, pharmaceutical compositions comprising such compounds, and methods treating subjects suffering from a condition, disease, or disorder that can be ameliorated by the administration of an inhibitor of tryptase, e.g., asthma and inflammatory diseases, to name only a few.

Abstract: The invention provides piperidine and piperazine derivatives of general formula (I), processes for their preparation, pharmaceutical compositions containing them, a process for preparing the pharmaceutical compositions, and their use in therapy

Abstract: The present invention relates to compounds of formula (I) wherein R1, R2, R3, R4, X, W, m and n are as defined hereinabove. The compounds are useful for the treatment and/or prophylaxis of diseases which are associated with 2,3-oxidosqualene-lanosterol cyclase such as hypercholesterolemia, hyperlipemia, arteriosclerosis, vascular diseases, mycoses, parasite infections, gallstones, tumors and/or hyperproliferative disorders, and treatment and/or prophylaxis of impaired glucose tolerance and diabetes.

Abstract: The invention relates to sulfonyl amine derivatives of formula IA wherein R5A, X1, X2, R9 and R10 are as defined herein, which derivatives are useful as bradykinin B1 receptor antagonists.

Abstract: Compounds, compositions and methods for altering insulin secretion, particularly in the context of treatment of subjects having, or suspected of being at risk for having, diabetes mellitus. The compounds have the following structure (I): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein W1, W2, X, R1, R2, R3, R4, m and n are defined herein.

Abstract: Spontaneously dispersible pharmaceutical compositions comprising a piperidine, e.g. 1-acylpiperidine Substance P Antagonist and its use in the treatment of CNS disorders, e.g. depression and social phobia, and respiratory diseases, e.g. asthma and chronic bronchitis.

Abstract: Disclosed are compounds which are inhibitors of metalloproteases and which are effective in treating conditions characterized by excess activity of these enzymes. In particular, the compounds have a structure according to the following Formula (I): where R1, R2, R3, n, A, E, X, G, G?, M and Z have the meanings described in the specification and the claims, as well as optical isomers, diastereomers and enantiomers of Formula I, and pharmaceutically-acceptable salts, biohydrolyzable amides, esters, and imides thereof. Also described are pharmaceutical compositions comprising these compounds, and methods of treating metalloprotease-related maladies using the compounds or the pharmaceutical compositions.

Abstract: The invention provides compounds of general formula wherein R1, m, Q, T, n, R2, R3, V, W, X and R4 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.

Abstract: Cis-2,6-disubstituted piperdine analogs, or lobeline analogs, having the general formula: are used to treat diseases of the central nervous system, drug abuse and withdrawal therefrom as well as to treating eating disorders.

Abstract: The present invention provides basic ionic contrast agents that have anticoagulant activity. The contrast media incorporate a lysine or arginine group or derivative, and have a free amino or guanidino group. Methods of using the contrast media are also disclosed.

Abstract: mGluR5 antagonists are used for the treatment and prevention of disorders, including Fragile X, autism, mental retardation, schizophrenia and Down's Syndrome. The methods of the invention can be used to treat epilepsy and anxiety in a human having Fragile X syndrome, autism, mental retardation, schizophrenia and Down's Syndrome.

Abstract: The present invention provides methods to treat or prevent neoplasia disorders in a mammal using a combination of a matrix metalloproteinase inhibitor and an antineoplastic agent.

Abstract: (R)-6F-phenylephrine, essentially free of (S)-6F-phenylephrine, and an anesthetic formulation comprising (R)-6F-epinephrin or (R)-6F-phenylephrine and having improved stability compared to formulations containing their non-fluorinated analog, are disclosed. Further disclosed is a method of providing vasoconstriction in a mammal by administering the anesthetic formulation. The anesthetic composition can include an anesthetic, an (R)-chiral compound having the structure: wherein R1, R2, and R4 are independently selected from —H or —F, at least one of R1, R2, and R4 is —F, and R3 is selected from —OH, —H or —F, or a pharmaceutically acceptable salt or ester thereof, said vasoconstrictor being essentially free of the (S)-chiral form. Also, a method of chiral addition of cyanide to a ring-fluorinated phenaldehyde, employing an almond hydroxynitrile lyase enzyme, provided in the form of a reversibly soluble polymer conjugate ((R)-Finezyme™-H series biocatalysts) is disclosed.

Abstract: The present invention provides 1,4 substituted piperazines, 1,4 substituted piperidines, and 1-substituted, 4-alkylidenyl piperidines compounds. The compounds of the invention are dual acting molecules having both leukotriene inhibition properties as well as antihistaminergic properties. The compounds of the invention are useful for treating conditions in which there is likely to be a histamine and/or leukotriene component. These conditions include preferably asthma, seasonal and perennial allergic rhinitis, sinusitus, conjunctivitis, food allergy, scombroid poisoning, psoriasis, urticaria, pruritus, eczema, rheumatoid arthritis, inflammatory bowel disease, chronic obsructive pulmonary disease, thrombotic disease and otitis media. Also provided are methods of treating asthma and rhinitis by administering an effective asthma and rhinitis-relieving amount of the compounds to a subject in need thereof.

Abstract: Compositions and uses of mGluR5 antagonists for the treatment and prevention of neurological disorders, such as Fragile X, autism, mental retardation, schizophrenia and Down's Syndrome, are disclosed.

Abstract: FK506 and geldanamycin promote nerve regeneration by a common mechanism that involves the binding of these compounds to polypeptide components of steroid receptor-complexes other than the steroid hormone binding portion of the complex (FKBP52 and hsp90, respectively). These and other agents cause hsp90 dissociation from steroid receptor complexes or block association of hsp90 with steroid receptor complexes.

Abstract: The present invention relates to a method for reducing inflammation in the skin and/or treating inflammatory skin disorders, pain, or pruritis by topically applying a composition comprising totarol or a pharmaceutically-acceptable ester thereof.

Abstract: A compound of formula (I): wherein: Ring A is a nitrogen linked mono or bicyclic heterocyclic ring as defined within; R1 and R2 are independently C1-3alkyl optionally substituted by fluoro or chloro; or R1 and R2 together with the carbon atom to which they are attached, form a C3-5cycloalkyl ring optionally substituted by fluoro; R3 is defined within; and n is 0-5; wherein the values of R3 may be the same or different; or a pharmaceutically acceptable salt or an in vivo hydrolysable ester thereof is described. The use of compounds of formula (I) in the production of an elevation of PDH activity in a warm-blooded animal such as a human being are also described. Pharmaceutical compositions, methods and processes for preparation of compounds of formula (I) are detailed.

Abstract: Compounds according to the following formula (I): wherein the variables Q and R1 to R6 are as described herein, which reversibly inhibit the cysteine proteases, such as cathepsins K, S, F, L and B; pharmaceutical compositions containing such compounds, and method of treating diseases and pathological conditions exacerbated by these cysteine proteases such as, but not limited to rheumatoid arthritis, multiple sclerosis and other autoimmune diseases, osteoporosis, asthma, Alzheimer's disease, atherosclerosis and endometriosis.

Abstract: The invention relates to novel compounds having formula (I) wherein Cy, X, Y, L and R1-6 are as defined herein. The compounds bind CD11/CD18 adhesion receptors such as Lymphocyte Function-associated Antigen-1 (LFA-1) and are therefore useful for treating disorders mediated by LFA-1 such as inflammation and autoimmune diseases.

Abstract: A cyclic amine compound represented by the following general formula (1): wherein, R1, R2 and R3 each independently represent a hydrogen atom or an alkoxy group; W1 and W2 each independently represent N or CH; X represents O, NR4, CONR4 or NR4CO; R4 represents a hydrogen atom, or an alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl group; and l, m and n each represents a number of 0 or 1, a salt thereof and a hydrate thereof are provided. These compounds have inhibitory effects on both cell adhesion and cell infiltration and are useful as anti-asthmatic agents, anti-allergic agents, anti-rheumatic agents, anti-arteriosclerotic agents, anti-inflammatory agents, anti-Sjogren's syndrome agents or the like.

Abstract: The present invention provides methods of treating diabetic cardiomyopathy, the methods comprising administering to a patient having or at risk of having diabetic cardiomyopathy a therapeutically effective amount of a glycogen phosphorylase inhibitor.

Abstract: The present invention relates to a compound having formula I: and pharmaceutically acceptable salts thereof. The compounds of formula I and pharmaceutical compositions containing them are of the class of thrombin inhibitors which are useful as anticoagulants.

Abstract: The present application describes modulators of CCR3 of formula (I): or pharmaceutically acceptable salt forms thereof, useful for the prevention of inflammatory diseases such as asthma and other allergic diseases.

Abstract: A method of using an MMP inhibitor and optionally radiation therapy, and one or more antineoplastic agents of the topoisomerase class selected from the group consisting of irinotecan and topotecan, as a combination therapy for the treatment of neoplasia is disclosed.

Abstract: The invention provides compounds which are useful as inhibitors of metalloproteases, and which are effective in treating conditions characterized by excess activity of these enzymes. In particular, the present invention relates to a compound having a structure according to Formula (I). Also disclosed are compounds, pharmaceutical compositions and methods of treating diseases characterized by metalloprotease activity using these compounds or the pharmaceutical compositions containing them.