Abstract: The invention relates to a process for the preparation of cyclic carboxylic acid orthoester fluorides in which a) at least one bis(alkylthio)carbenium salt is reacted with at least one organic compound containing at least two hydroxyl groups in the presence of at least one base, b) and subsequently, preferably in situ, the resultant thioorthoester is subjected to oxidative fluorodesulfurisation using a fluorinating agent and an oxidant to give the cyclic carboxylic acid orthoester fluoride.

Abstract: This invention relates to benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds, all of which may be described by of Formula I The invention is particularly related to such compounds that bind with high selectivity and high affinity to the benzodiazepine site of GABAA receptors. This invention also relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in treatment of certain central nervous system (CNS) diseases. Novel processes for preparing compounds of Formula I are disclosed. This invention also relates to the use of benzimidazoles, pyridylimidazoles and related bicyclic heteroaryl compounds of Formula I in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. Additionally this invention relates to the use such compounds as probes for the localization of GABAA receptors in tissue sections.

Abstract: The present invention provides amino ceramide-like compounds which inhibit glucosyl ceramide (GlyCer) formation by inhibiting the enzyme GlyCer synthase, thereby lowering the level of glycosphingolipids. The compounds of the present invention have improved GlcCer synthase inhibition activity and are therefore useful in therapeutic methods for treating various conditions and diseases associated with altered glycosphingolipid levels.

Abstract: The present invention relates to a series of substituted pyrimidines, to pharmaceutical compositions which contain them, to methods for their preparation and to their use in therapy, particularly in the treatment of neurodegenerative or other neurological disorders of the central and peripheral nervous systems.

Abstract: The present invention provides methods to treat or prevent neoplasia disorders in a mammal using a combination of a matrix metalloproteinase inhibitor and an antineoplastic agent.

Abstract: This invention discloses quinoxalinones which display inhibitory effects on serine proteases such as factor Xa, thrombin, and/or factor VIIa. The invention also discloses pharmaceutically acceptable salts and prodrugs of the compounds, pharmaceutically acceptable compositions comprising the compounds, their salts or prodrugs, and methods of using them as therapeutic agents for treating or preventing disease states in mammals characterized by abnormal thrombosis.

Abstract: This invention concerns compounds of formula the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein ?X1—X2—X3— is a trivalent radical,; >Y1—Y2— is a trivalent radical; r and s are each independently 0, 1, 2, 3, 4 or 5; t is 0, 1, 2 or 3; each R1 and R2 are independently hydroxy, halo, cyano, C1-6alkyl, trihalomethyl, trihalomethoxy, C2-6alkenyl, C1-6alkyloxy, hydroxyC1-6alkyloxy, C1-6alkylthio, C1-6alkyloxyC1-6alkyloxy, C1-6alkyloxycarbonyl, aminoC1-6alkyloxy, mono- or di(C1-6alkyl)amino, mono- or di(C1-6alkylaminoC1-6alkyloxy, aryl, arylC1-6alkyl, aryloxy or arylC1-6alkyloxy, hydroxycarbonyl, C1-6alkyloxycarbonyl; or two R1 or R2 on adjacent positions form together a bivalent radical; R3 is hydrogen, halo, C1-6alkyl, cyano, haloC1-6alkyl, hydroxyC1-6alkyl, cyanoC1-6alkyl, aminoC1-6alkyl, C1-6alkyloxyC1-6alkyl, C1-6alkylthio-C1-6alkyl, aminocarbonylC1-6alkyl, hydroxycarbonyl, hydroxycarbonylC1-6alkyl, C1-6alkyoxycarbonylC1-6alkyl, C1-6alkylcarbonylC

Abstract: The present invention relates to nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates, compositions comprising such compounds, methods of using such compounds and compositions, and to a method for the preparation of nitric oxide-releasing amidine- and enamine-derived diazeniumdiolates via the direct reaction of nitric oxide with amidines and enamines, and to a method of converting amines into such compounds.

Abstract: Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.

Abstract: Disclosed are MC-3/MC-4 receptor ligands, the ligands having the following formula: wherein A is a conformationally restricted ring system selected from the group consisting of: a) non-aromatic carbocyclic rings; b) aromatic carbocyclic rings; c) non-aromatic heterocyclic rings; d) aromatic heterocyclic rings; wherein said rings comprises from 5 to 8 atoms; and W is a unit which preferable comprises D-1-fluorophenyalanine, Y comprises a heteroatom, and Z comprises an aromatic carbocyclic ring. Also disclosed are pharmaceutical compositions comprising the ligands of the invention as well as methods of treating diseases mediated through MC-3/MC-4 receptors.

Abstract: The present invention relates to IL-5 inhibiting 6-azauracil derivatives useful for treating eosinophil-dependent inflammatory diseases, to processes and intermediates for their preparation as well as to pharmaceutical compositions comprising the said derivatives. It further relates to the use of such derivatives as a medicine, and to processes for marking a receptor or imaging an organ using the said derivatives.

Abstract: The invention is directed to 4h-benzo[1,4]oxazin-3-ones useful as peroxisome proliferator activated receptor gamma (PPAR?) agonists or antagonists. Pharmaceutical compositions comprising compounds of the present invention and methods of treating conditions such as NIDDM and obesity are also disclosed.

Abstract: Selected compounds of formula (I) are antibacterial agents: formula (I) wherein R2 represents a substituted or unsubstituted C1-C6 alkyl, cycloalkyl (C1-C6 alkyl)- or aryl (C1-C6 alkyl)-group, and A represents a group of formula (IA), or (IB) wherein R4 represents the side chain of a natural or non-natural alpha amino acid, and R5 and R6 are each independently hydrogen or C1-C6 alkyl, heterocyclic or aryl (C1-C6 alkyl)-, R5 and R6 when taken together with the nitrogen atom to which they are attached from an optionally substituted saturated heterocyclic ring of 3 to 8 atoms which ring is optionally fused to a carbocyclic or second heterocyclic ring

Abstract: Disclosed is a novel class of substituted imidazole compounds, pharmaceutical compositions containing them and uses of these compounds in the treatment and/or prevention of diseases and disorders related to the histamine H3 receptor. More particularly, these compounds are useful for the treatment and/or prevention of diseases and disorders in which an interaction with the histamine H3 receptor is beneficial. These imidazoles compounds have the formula I wherein R1, R2, R3, R4, R5, R6, A, X, Y and Z are as defined in the specification.

Abstract: The invention relates to substituted polycyclic aryl and heteroaryl pyrazinone compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.

Abstract: Novel substituted hexahydropyrrolo[1,2-a]pyrazines, octahydropyrido[1,2-a]-pyrazines and decahydropyrazino[1,2-a]azepines, use of these compounds as pharmaceutical compositions, pharmaceutical compositions comprising the compounds, and a method of treatment employing these compounds and compositions. The compounds show a high and selective binding affinity to the histamine H3 receptor indicating histamine H3 receptor antagonistic, inverse agonistic or agonistic activity. As a result, the compounds are useful for the treatment of diseases and disorders related to the histamine H3 receptor.

Abstract: Substituted porphyrin and azaporphyrin deviations with various substitutents in the 12- and 17-positions of the porphyrin skeleton as pharmaceutical agents for use in photodynamic therapy, MRI diagnosis, and radiodiagnostics.

Abstract: The present application describes nitrogen containing heteroaromatics and derivatives thereof of formula I: or pharmaceutically acceptable salt forms thereof, wherein rings D-E represent guanidine mimics, which are useful as inhibitors of factor Xa.

Abstract: The present application describes novel hydantoin derivatives of formula (I): or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, B, R1, R2, R3, R4, R5, R6, R7, R11, and n are defined in the present specification, which are useful as inhibitors of matrix metalloproteinases (MMP), TNF-? converting enzyme (TACE), aggrecanase, or a combination thereof.

Abstract: The present invention concerns alkyl aryl carbonyl compounds that possess anti-infective activity. The compounds of the invention can be used to target specific nuclear localization signal, thereby blocking importation of specific proteins or molecular complex into the nucleus of a cell. The invention encompasses methods of use of such compounds for treatment or prevention of infectious diseases, such as parasitic and viral diseases, including, for example, malaria and acquired immunodeficiency syndrome. The use of the compounds to detect certain specific protein structures which are present in nuclear localization sequences is also taught.