Abstract: A method of treating a patient suffering from pancreatitis comprising treating said patient with a therapeutically effective amount of a cholinergic agonist selective for an ?7 nicotinic receptor in an amount sufficient to decrease the amount of the proinflammatory cytokine that is released from a macrophage wherein said condition is acute pancreatitis. The compounds of the present invention include a quaternary analog of cocaine; (1-aza-bicyclo[2.2.2]oct-3-yl)-carbamic acid 1-(2-fluorophenyl)-ethyl ester; a compound of formula (I), a compound of formula (II), a compound of formula (III), a compound of formula (IV), and an oligonucleotide or mimetic capable of attenuating the symptoms of acute pancreatitis wherein the oligonucleotide or mimetic consists essentially of a sequence greater than 5 nucleotides long that is complementary to an mRNA of an ?7 cholinergic receptor. The variables of formulae (I), (II), (III) and (IV) are described herein.

Abstract: The present invention provides an antitumor agent and the like, which comprises as an active ingredient, a pyrimidine derivative represented by Formula (I): [wherein —X—Y—Z— represents —O—CR3?N— (wherein R3 represents a hydrogen atom, a substituted or unsubstituted aromatic heterocyclic group and the like) and the like, R1 represents —NR10R11 (wherein R10 and R11 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl and the like) and the like, R2 represents —NR13R14 (wherein R13 and R14 may be the same or different, and each represents a hydrogen atom, substituted or unsubstituted lower alkyl and the like)] or a pharmaceutically acceptable salt thereof.

Abstract: The present invention is directed to novel substituted fused aminopiperidines of structural formula (I) which are inhibitors of the dipeptidyl peptidase-4 enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-4 enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-4 enzyme is involved.

Abstract: Disclosed are novel gamma secretase inhibitors of the formula (I): or a pharmaceutically acceptable salt, solvate, or ester thereof, wherein L1, n, X, Ar, Y, Z, Q, and Q1 are as defined herein. Also disclosed are methods for inhibiting gamma secretase, methods for treating Alzheimer's disease, methods of treating one or more neurodegenerative diseases, and methods of inhibiting the deposition of amyloid protein (e.g., amyloid beta protein) in, on or around neurological tissue (e.g., the brain) using the compounds of formula 1.0.

Abstract: Compounds, pharmaceutical compositions and methods are provided that are useful in the treatment of CDK4-me-dialed disorders, such as cancer. The subject compounds arc gem-disubstituted or spimcyclic pyridine, pyrimidine and triazine derivatives.

Abstract: The invention includes tetrahydroquinoline and related compounds of formula I, and pharmaceutical compositions thereof, that exhibit useful antibacterial activity against a wide range of human and veterinary pathogens.

Abstract: Selected compounds are effective for prophylaxis and treatment of inflammation and inflammatory disorders, such as NIK-mediated disorders. 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, inflammation and the like.

Abstract: A method and composition for treating osteoarthritis with ion-channel regulators is disclosed. The ion-channel regulators are used alone or in combination with other osteoarthritis treatment agents, including but not limited to injectable agents such as viscosupplements and steroids. A composition comprising one or more ion-channel regulator(s) and one or more osteoarthritis treatment agent(s) is also disclosed.

Abstract: An objective of the present invention is to provide water-soluble prodrugs that can be administered parenterally, and which show excellent water solubility and small interspecies or individual differences and are rapidly converted to the active form by chemical conversion. This invention provides water-soluble prodrugs represented by formula (1), or pharmaceutically acceptable salts, or hydrates or solvates thereof, (wherein, R1 represents a hydrogen atom, or C1-C6 alkyl group; W represents a divalent group comprising a tertiary amino group or sulfonyl group; and Y represents a residue of a compound represented by Y—OH comprising an alcoholic hydroxyl group).

Abstract: The present invention provides methods and compositions for modulating levels of amyloid-? peptide (A?) exhibited by cells or tissues. The invention also provides pharmaceutical compositions and methods of screening for compounds that modulate A? levels. The invention also provides modulation of A? levels via selective modulation (e.g., inhibition) of ATP-dependent ?-secretase activity. The invention also provides methods of preventing, treating or ameliorating the symptoms of a disorder, including but not limited to an A?-related disorder, by administering a modulator of ?-secretase, including, but not limited to, a selective inhibitor of ATP-dependent ?-secretase activity or an agent that decreases the formation of active (or optimally active) ?-secretase. The invention also provides the use of inhibitors of ATP-dependent ?-secretase activity to prevent, treat or ameliorate the symptoms of Alzheimer's disease.

Abstract: The invention relates to compositions and methods for inhibiting RNA binding proteins (e.g., MEX-3, MEX-5 and POS-1), as well as methods for treating and preventing disorders associated with parasitic infections and inflammatory disorders.

Abstract: Dietary supplement compositions are disclosed. Methods of making and using dietary supplement compositions are also disclosed.

Abstract: The invention relates to novel pyrimidothienoindazoles of formula (I), processes for their preparation and their use for preparing medicaments for the treatment or prophylaxis of disorders, especially of hyperproliferative disorders.

Abstract: The present invention relates to compounds useful as inhibitors of treating tuberculosis.

Abstract: The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

Abstract: The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

Abstract: This invention provides a combination of ATP-competitive BCR-ABL inhibitor and a non-ATP competitive BCR-ABL inhibitor. The combination of the present invention may be used for treating cancers known to be associated with BCR-ABL.

Abstract: The present invention relates to compounds of Formula (Ia) or (Ib), the N-oxide forms, pharmaceutically acceptable addition salts, quaternary amines, stereoisomers, tautomers, racemics, metabolites, prodrugs, hydrates, or solvates thereof, wherein Y1, m, n, R1; X1; X2; R2; X3; X4; R3; and R4 have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to compounds that are kinase inhibitors useful for the treatment of disease states mediated by kinase, especially PLK4, in particular such compounds that are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

Abstract: A class of macrocyclic compounds of formula (I), wherein R1, R3, R4, Ra, Rb, A, B, Z, M, W and n are defined herein, that are useful as inhibitors of viral proteases, particularly the hepatitis C virus (HCV) NS3 protease, are provided. Also provided are processes for the synthesis and use of such macrocyclic compounds for treating or preventing HCV infection.

Abstract: The present invention relates to chemical compounds, methods for their discovery, and their therapeutic and research use. In particular, the present invention provides compounds as therapeutic agents against bacterial infections.

Abstract: The present invention relates to a new use for compounds that inhibit phosphodiesterase 1 (PDE1), e.g., that inhibit PDE1-mediated suppression of the dopamine D1 receptor and/or progesterone signaling pathways, including, e.g., methods of treatment or prophylaxis for conditions which may be ameliorated by enhancing the progesterone signaling response, particularly female sexual dysfunction.

Abstract: The present invention relates to compounds useful as inhibitors of Tec family protein kinases. These compounds have the general formula I: or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, G, Cy1, and X are as defined herein. 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: The invention relates to compounds and methods for inhibiting production and function of 3-deoxyglucosone and other alpha-dicarbonyl sugars in skin, by way of fructosamine-3-kinase inhibition, thereby treating or prevention various diseases, disorders or conditions. Additionally, the invention relates to treatment of various diseases, disorders or conditions associated with or mediated by oxidative stress since 3DG induces ROS and AGEs, which are associated with the inflammatory response caused by oxidative stress.

Abstract: The present invention comprises pyridopyrimidinediamine compounds of the general formula I: The compounds of the present invention are potent inhibitors of PTP1B. Accordingly, the invention also encompasses pharmaceutical compositions and methods of treating or preventing PTP-1B mediated diseases, including diabetes, obesity, and diabetes-related diseases.

Abstract: 1- or 2-substituted (6aR,9aS)-3-(phenylamino)-5-6a,7,8,9,9a-hexahydro-5-methyl-cyclopent[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyrimidin-4(1H or, 2H)-one compounds of Formula (I), processes for their production, their use as pharmaceuticals and pharmaceutical compositions comprising them.

Abstract: The present invention is related substituted enaminones represented by a compound of Formula I that are novel allosteric modulators of ?7 nAChRs. The invention also discloses the treatment of disorders that are responsive to enhancement of acetylcholine action on ?7 nAChRs in a mammal by administering an effective amount of a compound of Formula I.

Abstract: The invention is directed to novel sEH inhibitors and their use in the treatment of diseases mediated by the sEH enzyme. Specifically, the invention is directed to compounds according to Formula I: wherein R1, R2a, R2b, Rya, R6a, A, B, K, L, M, Y, Z, l, and m are defined herein, and to pharmaceutically-acceptable salts thereof. The compounds of the invention are sEH inhibitors and can be used in the treatment of diseases mediated by the sEH enzyme, such as hypertension. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting sEH and treatment of conditions associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Abstract: The invention relates to novel pyrimido-benzimidazole derivatives. Said products exhibit a good affinity for certain melanocortin receptor sub-types, in particular MC4 receptors. Said products represent a particular interest for treating pathological disorders and diseases associated with one or several melanocortin receptors. Pharmaceutical compositions containing said products and the use thereof for a drug preparation are also disclosed.

Abstract: Thiopheneprymidinone compounds useful in therapy, especially for use in the treatment and/or prevention of a steroid hormone dependent disorder, preferably a steroid hormone dependent disease or disorder requiring the inhibition of a 17?-hydroxysteroid dehydrogenase (17?-HSD) such as 17?-HSD type 1, type 2 or type 3 enzyme.

Abstract: The present invention relates generally to azatriocyclic containing pharmaceutical agents, and in particular, to azatricyclic metalloprotease inhibiting compounds. More particularly, the present invention provides a new class of azatricyclic MMP-3, MMP-8 and/or MMP-13 inhibiting compounds, that exhibit an increased potency and selectivity in relation to currently known MMP-13, MMP-8 and MMP-3 inhibitors.

Abstract: This invention relates to a stable pharmaceutical composition of freeze-dried tetrodotoxin powder which contains trace amount of tetrodotoxin, substances which can stabilizes tetrodotoxin, including disaccharide(s) or polyglucose(s) or analogues thereof and solvent(s), and solvents which can help tetrodotoxin dissolve.

Abstract: The present invention refers to the use of sodium channel blockers such as tetrodotoxin or saxitoxin, its analogues/derivatives as well as their acceptable salts, for the production of a medicament for the treatment of neuropathic pain resulting from chemotherapy.

Abstract: Compounds of formula (I) a tautomer or stereoisomer thereof, or a salt thereof, wherein ring B and the pyrimidine to which it is fused, R4, R5, R6 and R7 have the meanings as given in the description and the claims, are effective inhibitors of the Pi3K/Akt pathway.

Abstract: The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to compounds that are polo-like kinase (PLKs) inhibitors useful for the treatment of disease states mediated by PLK, especially PLK4, in particular such compounds that are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumour growth, rheumatoid arthritis, restenosis and atherosclerosis.

Abstract: The present invention relates to macrocyclic compounds of Formula I: or pharmaceutically acceptable salts thereof or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are JAK/ALK inhibitors useful in the treatment of JAK/ALK-associated diseases including, for example, inflammatory and autoimmune disorders, as well as cancer.

Abstract: The present invention relates to compounds or pharmaceutically-acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy. The invention particularly relates to certain indolin-2-ones and aza-indolin-2-ones which possess anti-tumour activity and are accordingly useful in methods of treatment of the human or animal body, in particular such compounds are useful in the treatment of pathological processes which involve an aberrant cellular proliferation, such as tumor growth, rheumatoid arthritis, restenosis and atherosclerosis.

Abstract: The invention relates to novel pyrimido-benzimidazole derivatives. Said products exhibit a good affinity for certain melanocortin receptor sub-types, in particular MC4 receptors. Said products represent a particular interest for treating pathological disorders and diseases associated with one or several melanocortin receptors. Pharmaceutical compositions containing said products and the use thereof for a drug preparation are also disclosed.

Abstract: The invention presents methods of identifying small molecule compounds that are activators of tumor suppressor protein p53 pathway, and its associated family members p63 and p73, function. The invention is further drawn to methods of killing tumor cells and treating cancers or other conditions requiring activation of the p53 family member pathways and DNA damage response pathways with the small molecules.

Abstract: The present invention is concerned with the use of PDE5 inhibitors in medicine.

Abstract: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein a1-a2=a3-a4 represents a divalent radical selected from N—CH?CH—CH, N—CH?N—CH or CH—CH?N—CH; Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR13—C1-5alkyl-, —C1-6alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O— or —NR11—; X2 represents —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen; R4 represents hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or R4 represents C1-4alkyloxy substituted with one or where possible two or more substituents selected from C1-4alkyloxy- or Het2-; R11 represents hydrogen; R12 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R13 represents Het14-C1-4alkyl, in particular morpholinyl-C1-4alkyl; Het2 represents a heterocycle selected from mor

Abstract: The present invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z1 and Z2 represent NH; Y represents —C3-9alkyl-, —C3-9alkenyl-, —C1-5alkyl-NR6—C1-5alkyl-, —C1-5alkyl-NR7—CO—C1-5alkyl-, —C1-6alkyl-CO—NH—, —C1-6alkyl-NH—CO—, —C1-2alkyl-CO-Het10-CO—, —C1-3alkyl-NH—CO-Het3-, -Het4-C1-3alkyl-CO—NH—C1-3alkyl-, —C1-2alkyl-NH—CO-L1-NH—, —NH—CO-L2-NH—, —C1-2alkyl-CO—NH-L3-CO—, —C1-2alkyl-NH—CO-L1-NH—CO—C1-3alkyl-, —C1-2alkyl-CO—NH-L3-CO—NH—C1-3alkyl-, —C1-2alkyl-NR11—CH2—CO—NH—C1-3alkyl-, Het5-CO—C1-2alkyl-, (C1-5alkyl-CO—NH—C1-3alkyl-CO—NH, —C1-5alkyl-NR13—CO—C1-3alkyl-NH—, —C1-3alkyl-NH—CO-Het27-CO—, or —C1-3alkyl-CO-Het28-CO—NH—; X1 represents a direct bond, O, —O—C1-2alkyl-, —CO—C1-2alkyl-, —NR16—C1-2alkyl-, —CO—NR17—, Het23-C1-2alkyl- or C1-2alkyl; X2 represents a direct bond, O, —O—C1-2alkyl-, —CO—C1-2alkyl-, —NR18—C1-2alkyl-, —CO—NR19—, Het24—C1-2alkyl- or C1-2alkyl; R1 and R5 each independen

Abstract: The present invention concerns the compounds of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR13—C1-5alkyl-, —C1-5alkyl-NR14—CO—C1-5alkyl-, —C1-2alkyl-NR21—H2—CO—NH—C1-3alkyl- or —C1-2alkyl-NR23—CO—CR16R17—NH—; X1 represents O or —O—C1-2alkyl-; X2 represents a direct bond, C1-2alkyl, —CO—C1-2alkyl or NR12—C1-2alkyl; R1 represents hydrogen or halo; R2 represents halo, acetylene or Het1; R3 represents hydrogen or cyano; R4 represents Ar4—C1-4alkyloxy-, C1-4alkyloxy- or C1-4alkyloxy substituted with one or where possible two or more substituents selected from Het2, NR7R8, hydroxy and C1-4alkyloxy-C1-4alkyloxy-; R7 represents hydrogen or C1-4alkyl; R8 represents C1-4alkyl substituted with NR25R26 or C1-4alkylsulfonyl; R12 represents hydrogen or C1-4alkyl-; R13 represents Ar6-sulfonyl or C1-6alkyloxycarbonyl optionally substituted with phenyl; R16 and R17 represents hydr

Abstract: The invention relates to the compounds isolated from Evodia rutaecarpa (Juss.), in that has been demonstrated to inhibit topoisomerase I. Evodiamine, an alkaloidal compound is reported the topoisomerase I inhibitory activity. The effect of evodiamine acts by stabilizing the covalent complex between topoisomerase I and DNA, which results in a blockade of DNA replication and transcription.

Abstract: Compositions and uses associated with the MT477 family of compounds are disclosed. Particular structural features and properties of the compounds are described in detail. Uses include administering an MT477 family member to a patient for therapeutic purposes. Compositions include chemicals belonging to the MT477 family and pharmaceuticals that contain such chemicals.

Abstract: Provided are compounds of the formula: wherein RN1 is a substituent of formula G1-NX1X2, wherein G1 is an optionally further substituted alkylene, which optionally forms, together with RN2, a cyclic group, and each of X1 and X2 is independently H or an N-substituent, or X1 and X2 together form a heterocyclic ring, or X1 together with G1 forms a cyclic group and X2 is H or an N-substituent; and each of Z1, Z2, Z3 and Z4 is H or a substituent, or two of Z1, Z2, Z3 and Z4 together form an optionally substituted ring, and further wherein at least one of Z1, Z2, Z3 and Z4 is other than H, and salts thereof, pharmaceutical compositions and methods of using the compounds. The compounds have antiviral activity.

Abstract: Compounds of formula: are disclosed. In these compounds is a heterocyclic ring. The compounds are useful as analgesics, anti-pruritics, anti-diarrheal agents, anticonvulsants, antitussives, anorexics/antiobesity agents and as treatments for hyperalgesia, drug addiction, respiratory depression, dyskinesia, pain (including neuropathic pain), irritable bowel syndrome and gastrointestinal motility disorders.

Abstract: Methods and pharmaceutical compositions relating to selective antagonists of the 5-HT6 receptor and 5-HT2A receptor useful for the treatment of cognitive disorders are presented.

Abstract: The present invention concerns the compounds of formula wherein Z represents NH; Y represents —C3-9alkyl-, —C2-9alkenyl-, —C3-7alkyl-CO—NH optionally substituted with amino, mono- or di(C1-4alkyl)amino or C1-4alkyloxycarbonylamino-, —C3-7alkenyl-CO—NH— optionally substituted with amino, mono- or di(C1-4alkyl)amino- or C1-4alkyloxycarbonylamino-, C1-5alkyl-NR13—C1-5alkyl-, —C1-5alkyl-NR14—CO—C1-5alkyl-, —C1-6alkyl-CO—NH—, —C1-5alkyl-CO NR15—C1-5alkyl-, —C1-3alkyl-NH—CO-Het20-, —C1-2alkyl-CO-Het21-CO—, —C1-2alkyl-NH—CO—CR16R17—NH—, —C1-2alkyl-CO—NH—CR18R19—CO—, —C1-2alkyl-CO—NR20—C1-3alkyl-CO—, or —NR22—CO—C1-3alkyl-NH—; X1 represents a direct bond, O or —O—C1-2alkyl-; X2 represents a direct bond, —CO—C1-2alkyl-, NR12, —NR12—C1-2alkyl-, —O—N?CH— or —C1-2alkyl-; R1 and R2 are hydrogen or halo; R3 are hydrogen; R4 represents hydrogen or C1-4alkyloxy; R12 and R13 are hydrogen or C1-4alkyl; R14 and R15 are hydrogen; R16 and R17 each independently represent hydrogen or C1-4alkyl; R18 and R19 are hydrogen or C1-

Abstract: The present invention relates to a new use of phosphodiesterase 1 (PDE1) inhibitors for the treatment and/or prophylaxis of narcolepsy.

Abstract: The present invention relates generally to azatriocyclic containing pharmaceutical agents, and in particular, to azatricyclic metalloprotease inhibiting compounds. More particularly, the present invention provides a new class of azatricyclic MMP-3, MMP-8 and/or MMP-13 inhibiting compounds, that exhibit an increased potency and selectivity in relation to currently known MMP-13, MMP-8 and MMP-3 inhibitors.