Abstract: The use of compounds of formula wherein R2, R3, R4, R5, R6 and R7 have several meanings, for the treatment of disorders mediated by protozoan organisms, novel compounds of the above formula and intermediates for the preparation of such compounds, pharmaceutical compositions comprising such novel compounds, a method of treating disorders mediated by protozoan organisms comprising administering such compounds, optionally together with a second drug substance, to a subject in need thereof and the use of such compounds, whenever comprising a photoaffinity label, for the identification of the molecular target(s) of arylamino alcohol antimalarials.

Abstract: The present invention is directed to compounds, their synthesis, and their use as antagonists, inverse agonists, modulators and or inhibitors of the Retinoic acid-related orphan nuclear receptor ?t (ROR?t)/ROR?. The compounds of the present invention are useful for modulating ROR?t)/ROR? activity and for treating diseases or conditions mediated by ROR?t)/ROR? such as for example, disease states associated with immunopathology of human autoimmune diseases such as Multiple Sclerosis (MS), Rheumatoid Arthritis (RA), Inflammatory Colitis, Psoriasis, COPD, Pain, Obesity, Diabetes, Dyslipidemia, Osteoporosis, Asthma, Neurodegenerative diseases and Cancer.

Abstract: 8-Substituted-2,6-methano-3-benzazocines of general structure are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.

Abstract: Compositions and methods for treatment of sexual dysfunctions by administering to a subject a pharmaceutical composition comprising a delta opioid receptor agonist in an amount effective to delay the onset of ejaculation in the subject during sexual stimulation.

Abstract: Disclosed is a melanin production inhibitor which has an excellent inhibitory activity on the production of melanin and is highly safe. The melanin production inhibitor is represented by general formula (1) (excluding clotrimazole) and/or a pharmacologically acceptable salt thereof. In the formula, A1, A2 and A3 are independently selected from a hydrogen atom, an aryl group which may have a substituent, and an aromatic heterocyclic group which may have a substituent.

Abstract: Compositions and methods for treatment of Parkinson's disease to reduce the negative side effects of the disease by administering a therapeutically effective diarylmethylpiperazine compound which exhibits delta opioid receptor agonist activity, and optionally, mu receptor antagonist activity.

Abstract: Compositions and methods for treatment of sexual dysfunctions by administering to a subject a pharmaceutical composition comprising a delta opioid receptor agonist in an amount effective to delay the onset of ejaculation in the subject during sexual stimulation.

Abstract: A composition of an antitussive, a decongestant, or an antihistamine to treat respiratory and oral pharyngeal congestion and related symptoms in a patient.

Abstract: The invention provides antihistamine drugs that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the antihistamine drug not attached to the water-soluble oligomer.

Abstract: In one aspect, the present invention features a method of producing a tablet including cetirizine including the steps of: (i) mixing cetirizine, a polyol, and a solvent for the cetirizine to form a cetirizine:polyol complex, wherein the solvent comprises water and an alkalizing agent and has a pH from about 2 to about 7; (ii) isolating particles of the cetirizine:polyol complex from the mixture; and (iii) forming the particles into a tablet.

Abstract: The present invention provides a compound of formula (IV) wherein R is Cl, Br, NO2, OH or OR?, and R? is alkyl, and its use in the synthesis of levocetirizine, including its use in the synthesis of (?)-1-[(4-chlorophenyl)-phenylmethyl]piperazine, an intermediate useful in the synthesis of levocetirizine. The present invention also provides compounds (II) and (III) which are useful in the synthesis of compound (IV).

Abstract: Compositions and methods for treatment of sexual dysfunctions by administering to a subject a pharmaceutical composition comprising a delta opioid receptor agonist in an amount effective to delay the onset of ejaculation in the subject during sexual stimulation.

Abstract: Compounds, compositions and methods are provided for the prophylaxis and treatment of infections caused by viruses of the Pneumovirinae subfamily of Paramyxoviridae and diseases associated with such infection.

Abstract: The present invention is based on the discovery of a cell-based system to identify novel modulators of splicing or splicing dependent processes. The cell-based system of the present invention utilizes a fast and highly sensitive reporter, that responds to defects in the splicing machinery itself and is sensitive to changes in the signals that regulate splicing dependent processes such as those that modulate the EJC, splicing-dependent export, localization or translation efficiency. The present invention further uses the cell-based screen to identify several small molecules that modulate both constitutive and alternative splicing. Accordingly, the present invention includes general or alternative splicing inhibitors identified using the assay described herein. The present invention also provides methods of treating a subject having a condition associated with aberrant target RNA expression.

Abstract: Compounds of general formula: as well as salts, enantiomers thereof and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain, depression and anxiety.

Abstract: The present invention provides compounds that are glycine transporter 1 (hereinafter referred to as GlyT-1) inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of GlyT1 such as cognitive disorders associated with Schizophrenia, ADHD (attention deficit hyperactivity disorder), MCI (mild cognitive impairment), and the like. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Abstract: Compounds of general formula: as well as salts, enantiomers thereof and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain, depression and anxiety.

Abstract: The invention relates to (among other things) oligomer-diarylpiperazine conjugates and related compounds. A conjugate of the invention, when administered by any of a number of administration routes, exhibits advantages over previously administered un-conjugated diarylpiperazine compounds.

Abstract: 8-Substituted-2,6-methano-3-benzazocines of general structure are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.

Abstract: The invention provides the compounds of formula (I) or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutical compositions comprising one or more compounds of formula I or intermediates thereof and one more of pharmaceutically acceptable carriers, vehicles or diluents. The invention further provides methods of preparation and methods of use of prodrugs including NO-releasing prodrugs, double prodrugs and mutual prodrugs comprising the compounds of formula I.

Abstract: The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.

Abstract: The compound of formula (8), in racemic or single enantiomeric form, is useful in making N-(diphenylmethyl)-piperazines such as cetirizine and levocetrizine. wherein Z is preferably phenyl.

Abstract: The present invention relates to the delivery of drug amines through an inhalation route. Specifically, it relates to aerosols containing drug amines that are used in inhalation therapy. In one aspect of the present invention, a method of delivering an amine drug in an aerosol form is provided. The method comprises: a) heating a coating, which includes an amine drug salt on a substrate contained in a device to a temperature sufficient to volatilize the amine drug from the coating, h) by said heating, forming an amine drug vapor, and c) during said heating, drawing air through said device, condensing said vapor to form aerosol particles containing less than 10% degradation products of the compound.

Abstract: Novel compounds of the general formula (I), 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 activators of PPAR? and should be useful for treating conditions mediated by the same.

Abstract: Disclosed is a melanin production inhibitor which has an excellent inhibitory activity on the production of melanin and is highly safe. The melanin production inhibitor comprises a compound represented by general formula (1) (excluding clotrimazole), and/or a pharmacologically acceptable salt thereof.

Abstract: A process for preparing pure levocetirizine and salts thereof, e.g., the levocetirizine dihydrochloride, and a pharmaceutical composition comprising levocetirizine dihydrochloride produced by the process are disclosed.

Abstract: The invention relates to at least one compound of general formula I wherein R1 is phenyl, pyridinyl, thienyl, furanyl, imidazolyl, pyrrolyl, triazolyl, thiazolyl, or pyridine N-oxide, where each R1 phenyl and R1 heteroaromatic ring may optionally and independently be substituted by 1, 2 or 3 substituents selected from CF3, methyl, iodo, bromo, fluoro, and chloro; R2 is independently selected from ethyl and isopropyl; R3 is hydrogen or fluoro; R4 is —NH2 or —NHSO2R5; and R5 is hydrogen, —CF3, or C1-C6 alkyl, or pharmaceutically acceptable salts thereof; at least one process for making at least one compound in accordance with Formula I; at least one method for treating at least one ? receptor associated condition with at least one compound in accordance with Formula I; and at least one pharmaceutical composition comprising at least one compound in accordance with Formula I.

Abstract: The present invention provides a compound of formula (IV) wherein R is Cl, Br, NO2, OH or OR?, and R? is alkyl, and its use in the synthesis of levocetirizine, including its use in the synthesis of (?)-1-[(4-chlorophenyl)-phenylmethyl]piperazine, an intermediate useful in the synthesis of levocetirizine. The present invention also provides compounds (II) and (III) which are useful in the synthesis of compound (IV).

Abstract: The present invention relates to a novel water based process for the preparation of substituted diphenylmethyl piperazines of Formula I and pharmaceutically acceptable salts wherein X1 and X2 represent independently a hydrogen, a halogen, a straight or branched chain lower alkyl, alkoxy or a hydroxyl radical and R is selected from groups such as acyl, alkyl, alkenyl, aralalkyl, aralalkenyl aralkyl, and aralalkenyl or aralkenyl hydroxyalkyl, aryloxyalkyl, alkoxyalkyl, aminoalkyl or its derivative comprising, reacting a compound of Formula II, with a compound of formula R—X where R is as defined above and X is suitable leaving group which includes halides, but not limiting use of other leaving groups such as tosylate, mesylate and activated acid groups such as acyl halide, anhydrides, mixed anhydrides etc. using water as a solvent, in presence of a catalyst and a base, at 25-100° C.

Abstract: The invention provides various methods comprising the administration of a CYP2D6 bioactive drug covalently bound to a water-soluble oligomer. Metabolism of CYP2D6 bioactive drug conjugates is diverted from CYP2D6 to alternative pathways, and the conjugates may therefore be utilized to alleviate the problems associated with interpopulation variation resulting from the genetic polymorphism in the CYP2D6 gene.

Abstract: Compounds of general formula: wherein R1, R2 and R3 are as defined in the specification, as well as salts, enantiomers thereof and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.

Abstract: The invention relates to at least one compound of general formula I wherein R1 is phenyl, pyridinyl, thienyl, furanyl, imidazolyl, pyrrolyl, triazolyl, thiazolyl, or pyridine N-oxide, where each R1 phenyl and R1 heteroaromatic ring may optionally and independently be substituted by 1, 2 or 3 substituents selected from CF3, methyl, iodo, bromo, fluoro, and chloro; R2 is independently selected from ethyl and isopropyl; R3 is hydrogen or fluoro; R4 is —NH2 or —NHSO2R5; and R5 is hydrogen, —CF3, or C1-C6 alkyl, or pharmaceutically acceptable salts thereof, at least one process for making at least one compound in accordance with Formula I; at least one method for treating at least one ? receptor associated condition with at least one compound in accordance with Formula I; and at least one pharmaceutical composition comprising at least one compound in accordance with Formula I.

Abstract: Thiourea compounds of the following formula: wherein n, R1, R2, R3, A1, A2, X, Y, and Z are defined herein. Also disclosed is a method of treating hepatitis C virus infection with these compounds.

Abstract: The present invention is related to 1-[(4-chlorophenyl)-phenylmethyl]-4-(2,2,2-trichloroethoxycarbonyl)-piperazine of the Formula (IV) and optically isomers thereof, process for preparation thereof and the use of the compound of the Formula (IV) in the preparation of 1-(4-chlorophenyl)-phenylmethyl-piperazine and optical isomers and salts thereof. 1-(4-chlorophenyl)-phenylmethyl-piperazine and optical isomers thereof are important intermediates in the preparation of non-sedating antihistamine-type active pharmaceutical ingredients.

Abstract: The invention relates to a method of deriving a peptidomimetic of a biologically active metallopeptide, wherein the peptidomimetic includes at least one non-peptide ring structure defining a template space superimposable on a corresponding defined template space of the metallopeptide, and where the peptidomimetic further includes at least two elements independently including an amino acid residue, amino acid side chain moiety or derivative thereof, the elements defining and occupying a similar descriptor space as corresponding elements of the metallopeptide. The invention further relates to peptidomimetics with a template space heterocyclic ring structure, including 5-, 6- and 8-membered and 5-5- and 6-5-bicyclic fused ring structure melanocortin receptor-specific peptidomimetics.

Abstract: Compounds of general formula: as well as salts, enantiomers thereof and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain, depression and anxiety.

Abstract: The invention provides antihistamine drugs that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the antihistamine drug not attached to the water-soluble oligomer.

Abstract: A compound of formula (8) or a salt thereof: wherein Z represents a group containing 1-20 carbon atoms and at least one chiral carbon atom and having a single conformation, is useful in the synthesis of pharmaceutical compounds, especially chiral compounds such as levocetirizine.

Abstract: The present invention relates to new N-methyl piperazine modulators of H1 receptor activity, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The present invention relates to (S)-2-[4-(4-chlorobenzhydryl)piperazin-1-yl]-ethoxyacetamide-(S)-pyrrolidone-5-carboxylic acid salt; (R)-2-[4-(4-chlorobenzhydryl)piperazin-1-yl]-ethoxyacetamide-(S)-pyrrolidone-5-carboxylic acid salt; (S)-2-[4-(4-chlorobenzhydryl)piperazin-1-yl]-ethoxyacetamide-(R)-pyrrolidone-5-carboxylicacid salt; or (R)-2-[4-(4-chlorobenzhydryl)piperazin-1-yl]-ethoxycetamide-(R)-pyrrolidone-5-carboxylic salt. The present invention relates also to a process for preparing (S)-2-[4-(4-chlorobenzhydryl)piperazin-1-yl]-ethoxyacetamide (I) and (R)-2-[4-(4-chlorobenzhydryl) piperazin-1-yl]-ethoxyacetamide (II) by chemical resolution of a mixture. These compounds are respectively intermediates for the synthesis of dextrocetirizine and levocetirizine.

Abstract: The present invention relates to a novel and commercially viable process for substantially optically pure levorotatory and dextrorotatory enantiomers of cetirizine intermediate, 1-[(4-chlorophenyl)phenylmethyl]piperazine, thereby producing substantially optically pure levorotatory and dextrorotatory enantiomers of cetirizine and their pharmaceutical acceptable acid addition salts thereof in high purity and in high yield using novel intermediates.

Abstract: The present invention is directed to substituted N-heterocycle derivatives, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.

Abstract: The present invention is related to 1-[(4-chlorophenyl)-phenylmethyl]-4-(2,2,2-trichloroethoxycarbonyl)-piperazine of the Formula (IV) and optically isomers thereof, process for preparation thereof and the use of the compound of the Formula (IV) in the preparation of 1-(4-chlorophenyl)-phenylmethyl-piperazine and optical isomers and salts thereof. 1-(4-chlorophenyl)-phenylmethyl-piperazine and optical isomers thereof are important intermediates in the preparation of non-sedating antihistamine-type active pharmaceutical ingredients.

Abstract: The present invention relates to new dibenzhydrylpiperazine modulators of histamine receptors, pharmaceutical compositions thereof, and methods of use thereof.

Abstract: The compound of formula (8), in racemic or single enantiomeric form, is useful in making N-(diphenylmethyl)-piperazines such as cetirizine and levocetrizine. wherein Z is preferably phenyl.

Abstract: The present invention provides compounds that are glycine transporter 1 (hereinafter referred to as GlyT-1) inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of GlyT1 such as cognitive disorders associated with Schizophrenia, ADHD (attention deficit hyperactivity disorder), MCI (mild cognitive impairment), and the like. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

Abstract: The present application describes deuterium-enriched levocetirizine, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

Abstract: The present application describes deuterium-enriched cetirizine, pharmaceutically acceptable salt forms thereof, and methods of treating using the same.

Abstract: Process for the synthesis of cetirizine dihydrochloride, wherein (a) a solution of {2-[4-(?-phenyl-p-chlorobenzyl)piperazin-1-yl]}ethanol in 1-7 volumes, referred to the weight of {2-[4-(?-phenyl-p-chlorobenzyl)piperazin-1-yl]}ethanol, of an organic solvent having a boiling point higher than 90° C. and being chosen from the group consisting of aliphatic, cycloalifatic or aromatic solvents is provided, whereafter (b) per equivalent of {2-[4-(?-phenyl-p-chlorobenzyl)piperazin-1-yl]}ethanol employed, 1-2 equivalents of a metal haloacetate or of haloacetic acid, as well as 3-7 equivalents of an alkaly metal hydroxyde are added to the solution as per (a), providing a reaction mixture, where 0.05-0.3 volumes, referred to the weight of {2-[4-(?-phenyl-p-chlorobenzyl)piperazin-1-yl]}ethanol employed, of water and 0.1-1.

Abstract: The present invention relates to a process for the preparation of {2-[4-(?-phenyl-p-chlorobenzyl)-piperazin-1-yl]-ethoxy}-acetic acid-N,N-dimethylamide of the Formula (I) and enantiomers thereof. The compound of the Formula (I) or enantiomers thereof are important pharmaceutical intermediates suitable for direct transformation into non-sedating antihistamine type pharmaceutical active ingredients cetirizine and levocetirizine.