Abstract: This invention relates to methods of treating traumatic brain injury (TBI) or hypoxic or ischemic stroke, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with either: (a) a sodium channel antagonist; (b) a nitric oxide synthase (NOS) inhibitor; (c) a glycine site antagonist; (d) a potassium channel opener; (e) an AMPA/kainate receptor antagonist; (f) a calcium channel antagonist; (g) a GABA-A receptor modulator (e.g., a GABA-A receptor agonist); or (h) an antiinflammatory agent. This invention also relates to methods of treating hypoxic or ischemic stroke comprising administering to a patient in need of such treatment an NMDA receptor antagonist in combination with a thrombolytic agent.

Abstract: Chemokine receptor antagonists, in particular, bicyclic diamine compounds of Formula (I) that act as antagonists of chemokine CCR2 and CCR3 receptors including pharmaceutical compositions and uses thereof to treat or prevent diseases associated with monocyte accumulation, lymphocyte accumulation or leucocyte accumulation are described herein.

Abstract: The present invention provides a compound of formula I These compounds are useful as antiviral agents, in particular, as agents against viruses of the herpes family.

Abstract: The present invention provides methods of treating cancer of the liver, ovarian cancer, a desmoid tumor, glioma, pancreatic cancer, or renal cell carcinoma using an estrogen agonist/antagonist. The present invention also provides kits that contain an estrogen agonist/antagonist for treating cancer of the liver, ovarian cancer, a desmoid tumor, glioma, pancreatic cancer, or renal cell carcinoma.

Abstract: The present invention relates to a method of making novel dipeptidyl peptidase-IV (“DPP-IV’) inhibitor compounds useful for treating, inter alia, diseases that are associated with proteins that are subject to processing by DPP-IV, such as Type 2 diabetes mellitus, metabolic syndrome (Syndrome X or insulin resistance syndrome), hyperglycemia, impaired glucose tolerance, glucosuria, metabolic acidosis, cataracts, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, Type 1 diabetes, obesity, hypertension, hyperlipidemia, atherosclerosis, osteoporosis, osteopenia, frailty, bone loss, bone fracture, acute coronary syndrome, infertility due to polycystic ovary syndrome, short bowel syndrome and to prevent disease progression in Type 2 diabetes. The invention also relates to a method of making 3,3,4,4-tetrafluoropyrrolidine, a starting material utilized in the afore-mentioned method for preparing DPP-IV compounds.

Abstract: A process is provide for the preparation of compounds of formula (I) herein comprising reacting a compound of formula (III), (IV) or (V) wherein the variables are as defined in the specification. The reaction is conducted in the presence of −OR3 and a hydroxide trapping agent or in the case of compounds of formula (IV) reacting in the presence of an auxiliary base and a hydroxide trapping agent.

Abstract: This invention relates to compounds of the formula and to pharmaceutically acceptable salts, prodrugs, and solvates thereof wherein X, Y, R1, R2, R3, R4, and R6 are as defined herein. The compounds of formula I are antibacterial and antiprotozoal agents that may be used to treat various bacterial and protozoal infections and disorders related to such infections. The invention also relates to pharmaceutical compositions containing the compounds of formula I, methods of making the compounds, and to methods of treating bacterial and protozoal infections by administering the compounds.

Abstract: The invention relates to substituted aryl and heteroaryl (R)-Chiral Halogenated 1-Substitutedamino-(n+1)-Alkanol compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery diseases. Novel high yield, stereoselective processes for the preparation of the chiral substituted alkanol compounds from chiral and achiral intermediates are described. Preferred (R)-Chiral 1-Substitutedamino-(n+1)-Alkanol compounds are substituted (R)-Chiral N,N-bis-phenyl aminoalcohols. A preferred specific (R)-Chiral N,N-bis phenyl aminoclcohol is the compound.

Abstract: The invention relates to compounds of formula I

Abstract: A long-acting antiparasitic formulation suitable for topical application including: (a) 0.1-50% w/v an avermectin or milbemycin having activity against endo- and/or ectoparasites; (b) 1-50% v/v a di(C2-4 glycol) mono(C1-4 alkyl) ether; (c) an optional antioxidant; and (d) an optional skin acceptable volatile solvent q.s. v/v.

Abstract: An efficient synthesis of sulfonyl pyrazoles of formula I: wherein the ring of the formula (R5)-A-(SOmR4), m, R1 through R9 are as defined in the specification, comprising reacting a compound of formula II: wherein the ring of the formula (R5)-A-(SOmR4), m R1 through R9 are as defined above and wherein R10 is halo, (C1-C6)alkyl-SO3—, (C6-C10)aryl-SO3—, (C1-C6)alkyl-SO2—, or (C6-C10)aryl-SO2—; wherein each of said (C1-C6)alkyl component of said (C1-C6)alkyl-SO3— and (C1-C6)alkyl-SO2— radicals may optionally be substituted on any carbon atom by one to six fluoro substituents per (C1-C6)alkyl component; with a compound of formula R3—H, wherein R3 is as defined above, in the presence of a fluoride containing salt and in the presence of a solvent.

Abstract: Compounds of general formula (I): wherein R1, R2, R3, R4, X, Y and A have the meanings given herein which are useful in the curative and prophylactic treatment of a medical condition for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.

Abstract: The invention provides compounds of formula I, R1—OP(O)(OH)2  I wherein R1 represents the non-hydroxy portion of a triazole antifungal compound of the type comprising a tertiary hydroxy group; or a pharmaceutically acceptable salt thereof. The compounds of the invention are useful in the treatment of fungal infections, and have good aqueous solubility.

Abstract: The invention features novel osteoregulin polypeptides, nucleic acid sequences which encode the polypeptides, vectors, antibodies, hosts which express heterologous osteoregulins, and animal cells and mammals with a targeted disruption of an osteoregulin gene. These osteoregulins play a role in regulating bone homeostasis, adiposity, and the calcification of atherosclerotic plaques. Accordingly, the invention also features screening assays to identify modulators of osteoregulin activity as well as methods of treating mammals for diseases or disorders associated with osteoregulin activity.

Abstract: A cell-based assay system in which the detection of the reporter gene activity, or secreted alkaline phosphatase (SEAP), is dependent upon the protease activity of the Hepatitis C virus NS3 gene product. This system can be used to assess the activity of candidate protease inhibitors in a mammalian cell-based assay system. The assay system is simpler than previously described assays due to the use of SEAP which allows the reporter gene activity to be quantified by measuring the amount of secreted gene product in the cell media by monitoring the conversion of luminescent or calorimetric alkaline phosphatase substrate.

Abstract: The present invention relates to substituted N-(cyclopropylmethyl)azacycloalkanes of the following formula (I): in which, independently, R1 is hydrogen or halogen, R2 is hydrogen or halogen and X is methylene or ethylene, their salts, the pharmaceutical compositions containing them, their use as antidiarrhoeal medicaments and methods for their preparation.

Abstract: The invention relates to substituted N-Alkyl/Alkenyl/Cycloalkyl/Heterocycyl N-Aryl/Heteroaryl tertiary-Heteroalkylamine compounds useful as inhibitors of cholesteryl ester transfer protein (CETP; plasma lipid transfer protein-I) and compounds, compositions and methods for treating atherosclerosis and other coronary artery disease. Preferred tertiary-heteroalkylamine compounds are substituted N-cycloalkyl N-benzyl aminoalcohols.

Abstract: The invention relates to triazolo[4,3-a]pyrido[2,3-d]pyrimidine-5-one derivatives, their regioisomers, their salts and their solvates if they exist, their preparation, compositions containing them and their use. These derivatives possess properties inhibiting PDE4 and/or the release of TNF&agr;, and may therefore be used for the treatment or prevention of numerous conditions by virtue of the inhibition of the PDE4 enzyme and the resulting increase in the cAMP level.

Abstract: A VEGF responsive cell-based assay for determining VEGF bioactivity is disclosed. The assay utilizes established signal transduction pathways in a method for determining VEGF bioactivity in a sample.

Abstract: Compounds of general formula I: or pharmaceutically or veterinarily acceptable salts, solvates, polymorphs or pro-drugs thereof wherein: wherein R1, R2, R3, R4, X and A have the meanings given herein which are useful in the curative and prophylactic treatment of a medical condition for which inhibition of a cyclic guanosine 3′,5′-monophosphate phosphodiesterase (e.g. cGMP PDE5) is desired.