Abstract: The present invention is directed to novel 1,2,4-thiadiazole derivatives useful as agonists or antagonists of the melanocortin receptor. More particularly, the compounds of the present invention are useful for the treatment of metabolic, CNS and dermatological disorders such as obesity, impaired oral glucose tolerance, elevated blood glucose levels, type II diabetes, Syndrome X, diabetic retinopathy, spinal cord injury, nerve injury, acute neurodegenerative disorders, chronic neurodegenerative disorders, plexopathies, male erectile dysfunction, dry eyes, acne, dry skin, aged skin, seborrheic dermatitis, rosacea, excessive ear wax, meibomian gland disorder, pseudofolliculitis, yeast infections, dandruff, hidradenitis suppurativa, ocular rosacea and eccrine gland disorder.

Abstract: The invention is directed to novel indazole peptidomimetic compounds which are useful as thrombin receptor antagonists for the treatment of diseases associated with thrombosis, restenosis, hypertension, heart failure, arrhythmia, inflammation, angina, stroke, atherosclerosis, ischemic conditions, Angiogenesis related disorders, cancer, and neurodegenerative disorders. Pharmaceutical compositions comprising the substituted indazole peptidomimetics of the present invention and methods of treating conditions mediated by the thrombin receptor are also disclosed.

Abstract: The present invention relates to an apparatus designed to perform chemical reaction kinetics studies and more particularly to an apparatus which is capable of conducting accelerated automated kinetics studies with user-defined temperature profiles and sampling periods. The apparatus includes at least one hot reaction block for heating one or more reaction vessels and at least one cold reaction block for cooling the one or more reaction vessels after heating thereof. The apparatus includes a robotic device for transferring one reaction vessel from one hot reaction block to one cold reaction block and a controller having a user interface for inputting a predetermined temperature profile and a predetermined sampling interval.

Abstract: The invention relates to novel pharmaceutically acceptable salts of anticonvulsant derivatives, processes for preparation of and pharmaceutical compositions containing said salts, useful in the treatment of epilepsy.

Abstract: Aminoguanidine and alkoxyguanidine compounds are described, including compounds of the Formula VII: wherein X is O or NR9 and Het, R1, R7, R8, R12—R15, Ra, Rb, Rc, Z, and n are set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof, that inhibit proteolytic enzymes such as thrombin. Also described are methods for preparing such compounds. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. The invention includes a composition for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation in a mammal, comprising a compound of the invention in a pharmaceutically acceptable carrier.

Abstract: Cyclic oxyguanidine pyrazinone compounds are described, including compounds of the Formula I: wherein R3, R4, R5, W, and A are as set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. Compositions for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation are described.

Abstract: The present invention relates to a method for monitoring the effect of in vivo administration of Cathepsin S inhibitors by measuring accumulation of an intermediate degradation product of invariant chain (Ii), in particular the p10 Ii fragment, in blood of dosed subjects.

Abstract: The invention is directed to a method of treating a neurodegenerative disorder in a subject in need thereof which comprises administering to the subject an amount of a compound effective to inhibit the interaction of amyloid-beta with alpha-7 nicotinic acetylcholine receptors.

Abstract: Cyclic oxyguanidine pyrazinone compounds are described, including compounds of the Formula I: wherein R3, R4, R5, W, and A are as set forth in the specification, as well as hydrates, solvates or pharmaceutically acceptable salts thereof. The compounds of the invention are potent inhibitors of proteases, especially trypsin-like serine proteases, such as chymotrypsin, trypsin, thrombin, plasmin and factor Xa. Certain of the compounds exhibit antithrombotic activity via direct, selective inhibition of thrombin. Compositions for inhibiting loss of blood platelets, inhibiting formation of blood platelet aggregates, inhibiting formation of fibrin, inhibiting thrombus formation, and inhibiting embolus formation are described.

Abstract: The invention is directed to nonpeptide substituted benzodiazepines of Formula I, wherein A, X, n, R1, R2, R3, R4, R5, a and b are as described in the specification, which are useful as vasopressin receptor antagonists for treating conditions associated with vasopressin receptor activity such as those involving increased vascular resistance and cardiac insufficiency. Pharmaceutical compositions comprising a compound of Formula I and methods of treating conditions such as hypertension, congestive heart failure, cardiac insufficiency, coronary vasospasm, cardiac ischemia, liver cirrhosis, renal vasospasm, renal failure, cerebral edema and ischemia, stroke, thrombosis, or water retention are also disclosed.

Abstract: DNAs encoding human voltage gated sodium channel ?1A subunit have been cloned and characterized. The recombinant protein is capable of forming biologically active protein. The cDNA's have been expressed in recombinant host cells that produce active recombinant protein. The recombinant protein is also purified from the recombinant host cells. In addition, the recombinant host cells are utilized to establish a method for identifying modulators of the receptor activity, and receptor modulators are identified.

Abstract: The present invention relates to certain substituted heterocycles of Formula (I) which are useful in the treatment of diseases related to lipid and carbohydrate metabolism, such as type 2 diabetes, adipocyte differentiation, uncontrolled proliferation, such as lymphoma, Hodgkin's Disease, leukemia, breast cancer, prostate cancer or cancers in general; and inflammation, such as osteoarthritis, rheumatoid arthritis, Crohn's Disease or Inflammatory Bowel Disease.

Abstract: Co-therapy for the treatment of neurological dysfunctions comprising administration of one or more fructopyranose sulfamates and erythropoietin.

Abstract: The present invention relates to novel substituted diamine derivatives for the formula wherein R1, R2, R3, R4, X1, X2, X3, X4, A, Y and n are as described in the specification, pharmaceutical compositions containing them and intermediates used in their manufacture. More particularly, the compounds of the invention are motilin receptor antagonists useful for the treatment of associated conditions and disorders such as gastrointestinal reflux disorders, eating disorders leading to obesity and irritable bowel syndrome.

Abstract: This invention provides novel arylindenopyridines of the formula: , and pharmaceutical compositions comprising same, useful for treating disorders ameliorated by reducing PDE activity in appropriate cells. This invention also provides therapeutic and prophylactic methods using the instant pharmaceutical compositions.

Abstract: This invention is directed towards novel alkylamide derivatives as bradykinin receptor antagonists useful for the treatment of bradykinin modulated disorders such as pain, inflammation, asthma and allergy. Furthermore, the present invention is directed to novel alkylamide derivatives as bradykinin receptor agonists useful for the treatment of bradykinin modulated disorders such as hypertension and the like.

Abstract: The present invention is directed to an implantable immune modulation device that is useful for modulating an immune response in mammals, comprising a plurality of fibers, within a porous shell. The fiber filling is loaded with single or multiple antigens, and optionally one or more biologically active compounds such as cytokines (e.g. lymphokines, chemokines etc.), attachment factors, genes, peptides, proteins, nucleotides, carbohydrates or cells depending on the application.

Abstract: Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described.

Abstract: Pyridoarylphenyl oxazolidinone compounds of the formula: in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.

Abstract: The invention relates to methods of synthesizing libraries of diverse and complex 2-substituted azole compounds of the general formula (I) or (II) wherein X, R2 and the ring components are as described herein, novel intermediates useful for synthesizing such substituted azole compounds and methods for identifying and isolating the compounds.