Abstract: The present invention relates to 3-aminopyrrolidine derivatives of the formula I: (wherein R1, R2, R3, R4, R5, R6, R7, R8, X, Y and X are as defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of chemokine receptors and more specifically as a modulator of the CCR2 and/or CCR5 receptor. The compounds and compositions of the invention may bind to chemokine receptors, e.g., the CCR2 and/or CCR5 chemokine receptors, and are useful for treating diseases associated with chemokine, e.g., CCR2 and/or CCR5, activity, such as atherosclerosis, restenosis, lupus, organ transplant rejection and rheumatoid arthritis.

Abstract: A NK1 antagonist having the formula (I), wherein Ar1 and Ar2 are optionally substituted phenyl or heteroaryl, X1 is an ether, thio or imino linkage, R4 and R5 are not both H or alkyl, and the remaining variables are as defined in the specification, useful for treating a number of disorders, including emesis, depression, anxiety and cough. Pharmaceutical compositions. Methods of treatment and combinations with other agents are also disclosed.

Abstract: The invention relates to methods of treating neurological disorders in a subject, by activating a DISC1 pathway. Methods of promoting neurogenesis in adult neural progenitor cells, enhancing nerve generation and treating GSK3 disorders as well as related compositions are also provided.

Abstract: The present invention relates to new sulfonamide derivatives of formula (I), wherein R1-R8 and Z are as defined in the claims, and optical antipodes or racemates and/or salts and/or hydrates and/or solvates thereof, which are selective antagonists of bradykinin B1, to processes for producing these same compounds, pharmacological compositions containing them and to their use in therapy or prevention of painful and inflammatory conditions.

Abstract: The invention relates to a compound of Formula (I): (A?)x-(A)-(B)-(Z)-(L)-(D), wherein: (A) is heteroaryl or aryl; each (A?), if present, is independently chosen from aryl, arylalkoxy, arylalkyl, heterocyclyl, aryloxy, halo, alkoxy, haloalkyl, cycloalkyl, haloalkoxy, and cyano, wherein each (A?) is substituted with 0, 1, 2, or 3 substituents independently chosen from halo, haloalkyl, aryl, arylalkoxy, alkyl, alkoxy, cyano, sulfonyl, amido, and sulfinyl; X is 0, 1, 2, or 3; (B) is a cyclopropyl ring, wherein (A) and (Z) are covalently bonded to different carbon atoms of (B); (Z) is —NH—; (L) is chosen from —CH2CH2—, —CH2CH2CH2—, and —CH2CH2CH2CH2—; and (D) is chosen from —N(—R1)—R2, —O—R3, and —S—R3, wherein: R1 and R2 are mutually linked to form a heterocyclic ring together with the nitrogen atom that R1 and R2 are attached to, wherein said heterocyclic ring has 0, 1, 2, or 3 substituents independently chosen from —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)(C1-C6 alkyl), alkyl, halo, cyano, alkoxy, haloalkyl, and

Abstract: Compounds according to formula (I) are effective for the treatment of broncho-obstructive and inflammatory diseases.

Abstract: The invention provides N-substituted benzenesulfonamides for use in treating or preventing cognitive disorders, such as Alzheimer's Disease. Compounds of particular interest are defined by Formula (I), wherein R1, R2, R3, R4, and R3?, are as described in the specification. The invention also encompasses pharmaceutical compositions comprising compounds of Formula (I) as well as methods of treating cognitive disorders, including Alzheimer's disease using compounds of Formula (I).

Abstract: The invention provides compounds which directly inhibit IRE-1? activity in vitro, prodrugs, and pharmaceutically acceptable salts thereof. Such compounds and prodrugs are useful for treating diseases associated with the unfolded protein response and can be used as single agents or in combination therapies.

Abstract: (R)-2-Arylpropionamide compounds of formula (I) are described. The process for their preparation and pharmaceutical preparations thereof are also described. The 2-Arylpropionamides of the invention are useful in the prevention and treatment of tissue damage due to the exacerbate recruitment of polymorphonuclear leukocytes (leukocytes PMN) and of monocytes at the inflammatory sites. In particular, the invention relates to the R enantiomers of omega-aminoalkylamides of 2-aryl propionic acids, of formula (I), for use in the inhibition of the chemotaxis of neutrophils and monocytes induced by the C5a fraction of the complement and by other chemotactic proteins whose biological activity is associated with activation of a 7-TD receptor. Selected compounds of formula (I) are dual inhibitors of both the C5a-induced chemotaxis of neutrophils and monocytes and the IL-8-induced chemotaxis of PMN leukocytes.

Abstract: Novel 5-membered iminocyclitol derivatives were found to be a potent and selective inhibitors of the glycoprotein processing ?- and ?-glucosidase which were further found to be active antiviral agents against Japanese encephalitis virus, dengue virus serotype 2 (DEN-2), human SARS coronavirus and human ?-hexosaminidase, a new target for development of osteoarthritis therapeutics.

Abstract: Compounds are described herein useful for treating diseases and conditions by modulation of one or more alpha adrenergic receptor, in particular the alpha 2C receptor. The compounds can include N-(2,3-substituted phenyl)-3,4-dihydro-2H-pyrrol-5-amine derivatives.

Abstract: The invention provides a method for obtaining local anesthetics encapsulated in liposomes, such as multi vesicular liposomes, with high encapsulation efficiency and slow release in vivo. When the encapsulated anesthetic is administered as a single intracutaneous dose, the duration of anesthesia and half-life of the drug at the local injection site is increased as compared to injection of unencapsulated anesthetic. The maximum tolerated dose of the encapsulated anesthetic is also markedly increased in the liposomal formulation over injection of unencapsulated anesthetic. These results show that the liposomal formulation of local anesthetic is useful for sustained local infiltration and nerve block anesthesia.

Abstract: The invention relates to azetidinyl, pyrrolidinyl, piperidinyl, and hexahydroazepinyl compounds of Formula I and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein R1-R3 and Z are defined as set forth in the specification. The invention is also directed to the use compounds of Formula I to treat, prevent or ameliorate a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain.

Abstract: Compounds are described herein useful for treating diseases and conditions by modulation of one or more alpha adrenergic receptor. The compounds can include a naphthalene, a quinoline, a benzoimidazole or an isoquinoline as a core structure. Methods of making, using and formulating these compounds are described.

Abstract: This invention provides new phenylpyrrolidine compounds, their use for the treatment or prevention of melatoninergic disorders and its compositions.

Abstract: The present invention relates to pyrrolin-2-ylamino compounds for combating animal pests. The invention also relates to a method for controlling animal pests by using these compounds, to plant propagation material and to an agricultural composition comprising said compounds. The invention also relates to a method for treating or protecting an animal from infestation or infection by parasites by using said compounds: wherein: A is a radical of the formulae A.1 or A.2: n, m, R1, R2, R3, R4, R5a, R5b, R5c, R5d, R5e, and R5f are defined herein.

Abstract: The invention provides organonitro compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat non-Hodgkin's lymphoma and certain leukemias in a patient. The compounds, compositions, kits, and methods are contemplated to provide a therapeutic benefit in treating non-Hodgkin's lymphoma, chronic lymphocytic leukemia, acute myelogenous leukemia, chronic myelogenous leukemia, and acute lymphoblastic leukemia. Exemplary organonitro compounds described herein include alkyl-substituted and acyl-substituted di-nitroheterocycles.

Abstract: Compounds of Formula (I) are disclosed; wherein XA, k, A, B, R3A, R3B, R4 and R5 are defined herein. The compounds of Formula (I) are HIV protease inhibitors. The compounds and their pharmaceutically acceptable salts are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

Abstract: Ischemia-reperfusion injury remains a primary cause of morbidity and mortality in individuals who experience disruption of normal blood flow to one or more major organs. For example, there are no clinically proven strategies that prevent acute renal failure following cardiac surgery. The present invention provides a variety of methods for the treatment or prevention of ischemia-reperfusion injury. In one aspect of the invention, a method for treating or preventing ischemia-reperfusion injury includes administering to a subject an effective amount of a sphingosine kinase inhibitor. Sphingosine kinase inhibitors are very effective in the protection against IR-induced acute renal failure and liver failure. Moreover, the effects occur very early after administration, requiring only a very short time of treatment. Toxicology studies with sphingosine kinase inhibitors demonstrate that they have low toxicity, even in long-term treatment.

Abstract: The invention relates to 5-HT6 receptor antagonists. Novel arylamine compounds and use of these compounds and their pharmaceutical compositions, e.g., in the treatment, modulation and/or prevention of physiological conditions associated with serotonin action, such as in treating obesity, and obesity-related disorders, e.g., cardiovascular disease, digestive disease, respiratory disease, cancer and type II diabetes; and psychological disorders such as schizophrenia, are disclosed.

Abstract: The invention provides a compound of formula (I), a solvate, a salt or prodrug thereof, useful in the treatment of diseases and conditions mediated by modulation of use-dependent voltage-gated sodium channels. Methods of treating epilepsy in a mammal are also provided.

Abstract: Disclosed are compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically related to GPR35, and/or GPR35-hERG signaling complex. For example, disclosed are compounds for preventing and/or treating diseases which are pathophysiologically related to GPR35 in a subject.

Abstract: This invention provides compounds of formula (I): wherein R1a, R1b, R1c, R2a, R2b, R2c, and R2d have values as described in the specification, useful as inhibitors of HDAC6. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of proliferative, inflammatory, infectious, neurological or cardiovascular diseases or disorders.

Abstract: The use of substituted amides for modulating the activity of 11?-hydroxysteroid dehydrogenase type 1 (11?HSD1) and the use of these compounds as pharmaceutical compositions, are described. Also a novel class of substituted amides, of the general formula I. Their use in therapy, pharmaceutical compositions comprising the compounds, as well as their use in the manufacture of medicaments are described. The present compounds are modulators and more specifically inhibitors of the activity of 11?HSDI and may be useful in the treatment of a range of medical disorders where a decreased intracellular concentration of active glucocorticoid is desirable.

Abstract: A compound represented by the following formula (1) or a salt thereof: The compound has an inhibitory activity on the production of interleukin-6, and is therefore useful as a therapeutic agent for a disease associated with interleukin-6, ocular inflammatory diseases and the like. In the formula, R1 represents a halogen atom, a hydrogen atom, a lower alkyl group which may have a substituent, a formyl group, or a lower alkylcarbonyl group which may have a substituent, R2 represents a bicyclic hydrocarbon group which may have a substituent or a bicyclic heterocyclic group which may have a substituent, R3 represents a hydrogen atom, a lower alkyl group which may have a substituent, an aryl group which may have a substituent, or an acyl group.

Abstract: Novel compounds which are useful for treating acute pain, visceral pain, neuropathic pain, inflammatory/pain receptor-mediated pain, tumour pain and headache diseases.

Abstract: Compounds having high angiogenesis inhibiting activity useful as agents for effective treatment and prevention of diseases involving pathologic angiogenesis, e.g.

Abstract: The present invention discloses novel naphthalenyloxypropenyl derivatives useful for inhibiting the enzyme activity of histone deacetylase, leading effective suppression of cancer cell proliferation.

Abstract: The use of substituted amides for modulating the activity of 11?-hydroxysteroid dehydrogenase type 1 (11?HSD1) and the use of these compounds as pharmaceutical compositions, are described. Also a novel class of substituted amides, of the general formula I. Their use in therapy, pharmaceutical compositions comprising the compounds, as well as their use in the manufacture of medicaments are described. The present compounds are modulators and more specifically inhibitors of the activity of 11?HSDI and may be useful in the treatment of a range of medical disorders where a decreased intracellular concentration of active glucocorticoid is desirable.

Abstract: The invention relates to phenylcyclopropylamine acetamide derivatives and their use in treating diseases.

Abstract: The present invention relates to 3-aminopyrrolidine derivatives of the formula I: (wherein R1, R2, R3, R4, R5, R6, R7, R8, X, Y and X are as defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of chemokine receptors and more specifically as a modulator of the CCR2 and/or CCR5 receptor. The compounds and compositions of the invention may bind to chemokine receptors, e.g., the CCR2 and/or CCR5 chemokine receptors, and are useful for treating diseases associated with chemokine, e.g., CCR2 and/or CCR5, activity, such as atherosclerosis, restenosis, lupus, organ transplant rejection and rheumatoid arthritis.

Abstract: The present invention provides sphingosine-1-phosphate analogs that are potent, and selective agonists at one or more S1P receptors, specifically the S1P1 receptor type. The compounds invention include compounds having a phosphate moiety as well as compounds with hydrolysis-resistant phosphate surrogates such as phosphonates, alpha-substituted phosphonates, and phosphothionates.

Abstract: Certain chemical entities are provided herein. Pharmaceutical compositions comprising at least one chemical entity and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one chemical entity effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Methods of treatment include administering at least one chemical entity as a single active agent or administering at least one chemical entity in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

Abstract: The present invention relates to a compound of formula I wherein Ar, R1, R2, R3, n, and o are as defined herein or to a pharmaceutically active salt, a racemic mixture, an enantiomer, an optical isomer or a tautomeric form thereof. The present compounds are high potential NK-3 receptor antagonists for the treatment of depression, pain, psychosis, Parkinson's disease, schizophrenia, anxiety and attention deficit hyperactivity disorder (ADHD).

Abstract: The present invention relates to an arylalkylamine compound represented by the following formula [I] or a pharmaceutically acceptable salt thereof, a process for preparing the same, and use of the above-mentioned compound as an activating compound (CaSR agonist) of a Ca sensing receptor, a pharmaceutical composition containing the above-mentioned compound as an effective ingredient, etc.

Abstract: The invention relates to the inhibition of histone deacetylase. The invention provides compounds and methods for inhibiting histone deacetylase enzymatic activity. The invention also provides compositions and methods for treating cell proliferative diseases and conditions. One aspect of the invention provides compounds of formula (1): in which T, A and X are as described herein.

Abstract: Methods for therapeutic renal denervation are disclosed herein. One aspect of the present application, for example, is directed to methods that block, reduce and/or inhibit renal sympathetic nerve activity to achieve a reduction in central sympathetic tone. Renal sympathetic nerve activity may be altered or modulated along the afferent and/or efferent pathway. The achieved reduction in central sympathetic tone may carry several therapeutic benefits across many disease states.

Abstract: The present invention relates to a pharmaceutical composition comprising specific compounds which may be obtained from Leontopodium alpinum Cass. (Edelweiss). A preferred compound is leoligin (=(2S,3R,4R)-4-(3,4-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)tetrahydrofuran-3-yl]methyl(2Z)-2-methylbut-2-enoat]). Corresponding means and methods in respect of medical uses of the compounds are described. The present invention also provides a medical device comprising, containing or having been contacted with the compound. The compounds provided herein may particularly be used in the treatment of hyperplastic diseases, in particular intimal hyperplasia, e.g. stenosis, restenosis, atherosclerosis and the like. Also envisaged herein is the use of these compounds in the treatment of proliferative diseases, such as leukemia, prostate cancer and lung cancer.

Abstract: Disclosed herein are novel compositions and methods for treating or preventing a variety of disorders and conditions associated with lipid metabolism. The methods generally include administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising one or more fibric acid or statin derivative compositions alone or in combination with one or more lipid altering agents and/or PDE inhibitors.

Abstract: The present invention relates to pyrrolin-2-ylamino compounds for combating animal pests. The invention also relates to a method for controlling animal pests by using these compounds, to plant propagation material and to an agricultural composition comprising said compounds. The invention also relates to a method for treating or protecting an animal from infestation or infection by parasites by using said compounds. wherein n is 0, 1, 2, 3, 4 or 5; m is 0, 1, 2, 3, 4 or 5; R1, R2 are each independently selected from the group consisting of: halogen, CN, N3, NO2, C1-C6-alkyl, C2-C6-alkenyl and C2-C6-alkynyl, where the last 3 radicals mentioned may be partly or completely halogenated and/or may carry any combination of 1, 2 or 3 radicals R#, etc.

Abstract: Novel compounds of the general formula (I), in which the variables are as defined in claim 1, the use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds and methods of treatment employing these compounds and compositions. The present compounds are useful in the treatment and/or prevention of conditions mediated by Peroxisome Proliferator-Activated Receptors (PPAR), in particular the PPAR? subtype, namely, type 1 diabetes, type 2 diabetes, dyslipidaemia, syndrome X (including the metabolic syndrome, i.e. impaired glucose tolerance, insulin resistance, hyper-triglyceridaemia and/or obesity), cardiovascular diseases (including atherosclerosis) and hypercholesterolaemia.

Abstract: Sphingosine-1-phosphate analogs that are potent, and selective agonists at one or more S1P receptors, specifically the S1P1 receptor type are provided. The disclosed compounds include an optional phosphate moiety as well as compounds with hydrolysis-resistant phosphate surrogates such as phosphonates, alpha-substituted phosphonates, and phosphothionates.

Abstract: This invention relates to novel compounds of the Formula I, II, III, IHa, NIb, IV, IVa, IVb, IVc, IVd, IVe, V, Va, Vb1 V1, V1a, VIb, VII, Vi1a, VIIb, VIII, V111a, VIIIb, IX, IXa, X, and Xa, pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful for the therapeutic treatment of diseases associated with the modulation or inhibition of 11 ?-HSD1 in mammals. The invention further relates to pharmaceutical compositions of the novel compounds and methods for their use in the reduction or control of the production of Cortisol in a cell or the inhibition of the conversion of cortisone to Cortisol in a cell.

Abstract: The present application relates to pyrrolidine, piperidine, and other nitrogen-containing heterocyclic derivatives and the use of these compounds for treating and preventing pam or inflammation. The analgesic compounds demonstrate efficacy in the treatment of neuropathic pain resulting from a variety of conditions such as diabetic neuropathy, HIV infections, and post-herpetic neuralgia.

Abstract: Novel 5-membered iminocyclitol derivatives were found to be a potent and selective inhibitors of the glycoprotein processing ?- and ?-glucosidase which were further found to be active antiviral agents against Japanese encephalitis virus, dengue virus serotype 2 (DEN-2), human SARS coronavirus and human ?-hexosaminidase, a new target for development of osteoarthritis therapeutics.

Abstract: An optically active 3-aminopyrrolidine (3AP) salt has a high optical purity which is useful as an intermediate in an industrial production method of an optically active 3AP, an efficient method for producing it, and an efficient industrial method for optical resolution of 3AP. Optical resolution of 3AP is efficiently carried out by reacting racemic 3AP with optically active 2-methoxyphenylacetic acid in the presence of a mineral acid such as hydrochloric acid in an aqueous solvent, followed by separation of the resulting diastereomer salt constituted by 1 mole of optically active 3AP and 2 moles of optically active 2-methoxyphenylacetic acid.

Abstract: A CPT1 inhibitor compound is represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof: or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. A method of treating a subject having cancer comprises administering to the subject a therapeutically effective amount of a compound represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to compounds of the Formula (I) which are useful for treating conditions associated with mGluR3 receptors, such as depression, schizophrenia and migraine, pharmaceutical compositions thereof, and methods of using the same.

Abstract: The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino compounds can also inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases.

Abstract: The present invention relates to compounds comprising a cyclobutoxy group, processes for preparing them, phar-maceutical compositions comprising said compounds and their use as pharmaceuticals.