Abstract: The invention includes mouse serotonin 5-HT2c receptor isoforms having amino acid replacements at one or more positions of the natural mouse serotonin 5-HT2c receptor polypeptide sequence, specifically at one or more of positions 157, 159 and 161. The polypeptides are useful for identifying ligands which bind with the serotonin 5-HT2c receptor and modulators of the serotonin 5-HT2c, and for identifying drugs with affinity for 5-HT2 receptors which are used to treat schizophrenia, Parkinsonism, and anxiety disorders.

Abstract: A class of substituted 1,2,4-triazolo[4,3-b]pyridazine derivatives, possessing a fluoro-substituted phenyl ring at the 3-position and a heteroaryl-methoxy moiety at the 6-position, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.

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 present invention is concerned with a novel process for the preparation of 1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-one (CAS 30071-93-3). This compound is useful as an intermediate in the synthesis of therapeutic agents.

Abstract: Alicyclic imidazole compounds; pharmaceutically active compositions containing such compounds; and the use of such compounds in formulations for the control or prevention of disease states in which histamine H3 receptors are involved, such as allergy, inflammation, hypotension, glaucoma, sleeping disorders, states of hyper- and hypo-motility of the gastro-intestinal tract, cardiovascular disease, hypo- and hyper-activity of the central nervous system, Alzheimer's, schizophrenia, obesity and migraines are disclosed.

Abstract: The invention encompasses the novel class of compounds represented by formula I, which are inhibitors of the PTP-1B enzyme. The invention also encompasses pharmaceutical compositions and methods of treating or preventing PTP-1B mediated diseases, including diabetes, obesity, and diabetes-related diseases.

Abstract: The present invention is concerned with novel processes for the preparation of (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol. This compound is useful as an intermediate in the synthesis of compounds which possess pharmacological activity.

Abstract: The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

Abstract: A class of phenylsulphonyl derivatives wherein the sulphonyl moiety is also attached to an N-arylalkyl-substituted azetidine, pyrrolidine or piperidine ring are selective antagonists of the human 5-HT2A receptor and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of adverse conditions of the central nervous system, including schizophrenia and depression.

Abstract: The present invention relates to a novel enantioselective bioreduction using a yeast microorganism for the preparation of the chiral allylic alcohols of structural formula I (R is hydrogen or methyl) which are useful in the asymmetric synthesis of integrin &agr;v&bgr;3 receptor antagonists.

Abstract: Gamma-secretase inhibitors, useful in the treatment or prevention of Alzheimer's disease, are disclosed. The preferred compounds have, as the central portion of the molecule, the structure (a) and are di-astereoisomers of known protease inhibitors.

Abstract: The present invention is directed to compounds and pharmaceutical compositions comprising the compounds which are inhibitors of the enzyme gamma secretase and which are useful in the treatment or prevention of diseases in which the beta-amyloid peptide is involved, such as Alzheimer's disease.

Abstract: A class of pyrazino[2,3-d]pyridazine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 5-position, a substituted alkoxy moiety at the 3-position, and a range of substituents at the 2-position, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 and/or &agr;5 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse conditions of the central nervous system, including anxiety, convulsions and cognitive disorders.

Abstract: A class of substituted or 6,7-ring fused [1, 2, 3]triazolo[1,5-&agr;]-pyrimidine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent at the 3-position and an amino moiety at the 5-position, are selective ligands for GABAA receptors, in particular having high affinity for the &agr;2 and/or &agr;3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of disorders of the central nervous system, including anxiety and convulsions.

Abstract: Compounds having Formula I, including pharmaceutically acceptable salts, hydrates and solvates thereof: are selective inhibitors of the 11&bgr;-HSD1 enzyme. The compounds are useful for the treatment of diabetes, such as noninsulin-dependent diabetes (NIDDM), hyperglycemia, obesity, insulin resistance, dylsipidemia, hyperlipidemia, hypertension, Syndrome X, and other symptoms associated with NIDDM.

Abstract: This invention is concerned with mammalian metabolites of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)-phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which is a tachykinin receptor antagonist that is useful in the prevention and treatment of certain disorders, including emesis and psychiatric disorders such as depression and anxiety.

Abstract: The present invention relates compounds of the formula (I): wherein X represents hydrogen, C1-4alkyl optionally substituted by a hydroxy, methoxy or benzyloxy group, or CO2(C1-2alkyl); Z is —CR9R10CH2— or —CH2CR9R10—; and R1, R2, R3, R4, R5 and R6 are as defined herein. The compounds are of particular use in the treatment or prevention of depression, anxiety, pain, inflammation, migaine, emesis or postherpetic neuralgia.

Abstract: The present invention is directed to 3-phenylimidazol[4,5-b]pyridine derivatives, that are selective ligands for GABAA receptors. These compounds are useful in the treatment and prevention of disorders of the central nervous system, including anxiety and convulsions.

Abstract: A class of benzopyrancarboxylic acid derivatives comprises compounds that are potent agonists of PPAR alpha and/or gamma, and are therefore useful in the treatment, control or prevention of non-insulin dependent diabetes mellitus (NIDDM), hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, obesity, vascular restenosis, inflammation, and other PPAR alpha and/or gamma mediated diseases, disorders and conditions.

Abstract: The present invention is directed to compounds which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV 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-IV enzyme is involved.