Abstract: The invention relates to hydroxamic and carboxylic acid derivatives. Compounds of the formula: are disclosed. These compounds are useful for the treatment of diseases mediated by inhibitors of matrix metalloproteinase, ADAM, ADAM-TS enzymes, and/or TNF&agr;-mediated diseases including degenerative diseases and certain cancers.

Abstract: 4-(4-(-Chlorophenyl)piperazin-1-yl)sulfonylmethyl)-tetrahydor yran-4-carboxylic acid and the corresponding N-hydroxy amide, and derivatives thereof, are useful as therapeutic agents.

Abstract: N-oxides of formula (i) wherein R1 is CH3, CH2F, CHF2 or CF3; R2 is CH3 or CF3; R3 is F, Cl, Br, CN or CH3; and R4 is H, F, Cl, Br, CN or CH3; and pharmaceutically-acceptable salts thereof, are useful as therapeutic agents, e.g., for the treatment of inflammatory diseases.

Abstract: A unit dosage and pharmaceutical delivery system for anaesthetizing a human patient prior to major surgery, which comprise between 200 mg and 300 mg of levobupivacaine.

Abstract: Compounds of the formula B—X—(CH2)m—CR1R2—(CH2)n—CO—Y  (I) have therapeutic utility as inhibitors of metalloproteinases etc.

Abstract: A novel class or family of TGF-&bgr; binding proteins is disclosed. Also disclosed are assays for selecting molecules for increasing bone mineralization and methods for utilizing such molecules.

Abstract: The invention relates to hydroxamic and carboxylic acid derivatives. Compounds of the formula: are disclosed. These compounds are useful for the treatment of diseases mediated by inhibitors of matrix metalloproteinase, ADAM, ADAM-TS enzymes, and or INF&agr;-mediated diseases including degenerative diseases and certain cancers.

Abstract: Compounds having therapeutic utility are of the formula wherein NB2 is heterocycloalkyl and R1 and R2 are each various substituents or a cyclic group.

Abstract: The present invention pertains to compositions and methods for treating disease states which are capable of being modulated by inhibition of phosphodiesterase IV or Tumour Necrosis Factor, or that is a pathological condition associated with a function of phosphodiesterase IV, eosinophil accumulation or a function of the eosinophil, said method comprising administering to a person or animal in need of such treatment an effective amount of the compound of a formula wherein R1 is C1-3 alkyl optionally substituted with one or more fluorines; R2 is CH2OCH3 or 2 or 3-tetrahydrofuranyl; R3 is a pyrazole, imidazole or isoxazole group of partial formula (A), (B) or (C) R4 is C 1-3 alkyl; and R5 and R6, which may be the same or different, each represents C1-3 alkyl, halogen, CF3 or CN; or a pharmaceutically-acceptable salt thereof

Abstract: A process for the preparation of a compound of formula (1) comprises reacting compounds of formulae (2) and (3) in the presence of an enzyme, wherein A is a thiol-protecting group, B, C and D are each the same or different organic groups of up to 30 C atoms, optionally functionalized at any position, provided that neither a primary amine nor a primary amide is present, and X is a group that can be displaced by NH2.

Abstract: Levobupivacaine ((S)-1-butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide) is useful as an anesthetic, particularly in a patient who is disposed to adverse systemic side-effects, e.g., one who is CNS-compromised or predisposed to CNS side-effects. A unit dose of levobupivacaine comprising at least 75 mg to less than 200 mg of levobupivacaine is described herein.

Abstract: N-oxides of formula (i) wherein R1 is CH3, CH2F, CHF2 or CF3; R2 is CH3 or CF3; R3 is F, Cl, Br, CN or CH3; and R4 is H, F, Cl, Br, CN or CH3; and pharmaceutically-acceptable salts thereof, are useful as therapeutic agents, e.g., for the treatment of inflammatory diseases.

Abstract: A compound of the formula wherein R1 is C1-3 alkyl optionally substituted with one or more fluorines; R2 is C1-6 alkyl, cycloalkyl or NR4R5; R3 is a pyrazole, imidazole or isoxazole group of partial formula (A), (B) or (C) NR4R5 is a nitrogen-containing heterocyclic ring; R6 is C1-3 alkyl; and R7 and R8, which are the same or different, each represents C1-3 alkyl, halogen, CF3 or CN; or a pharmaceutically-acceptable salt thereof.

Abstract: A novel human protein has been isolated which is encoded by a nucleic acid molecule comprising the polynucleotide sequence provided in SEQ ID NO:1 or a polynucleotide sequence that is completely complementary thereto. This novel protein binds to at least two members of the family of TGF-beta proteins, which are the human bone morphogenic protein-5 and human bone morphogenic protein-6.

Abstract: Compounds of the formula (i) have therapeutic utility via inhibition of TNF or phosphodiesterase.

Abstract: A compound of the formula wherein R1 is C1-3 alkyl optionally substituted with one or more fluorines; R2 is CH2OCH3 or 2 or 3-tetrahydrofuranyl; R3 is a pyrazole, imidazole or isoxazole group of partial formula (A), (B) or (C)  R4 is C1-3 alkyl; and R5 and R6, which may be the same or different, each represents C1-3 alkyl, halogen, CF3 or CN; or a pharmaceutically-acceptable salt thereof.

Abstract: A process for preparing a substantially single enantiomer of tramadol, or a pharmaceutically-acceptable salt thereof, proceeds by means of a classical salt resolution using a substantially single enantiomer of O,O-di-p-toluoyltartaric acid as a resolving agent.

Abstract: Compounds that are inhibitors of phosphodiesterase and have therapeutic utility, are of formula (i) wherein R1 is C3-6 cycoalkyl, or C1-3 alkyl optionally substituted with one or more fluorine atoms; R2 is C1-6 alkyl, C3-6 cycloalkyl, CF3, CH2CF3, C2F5 or NR4R5; R3 is a pyrazole, imidazole or isoxazole group of partial formula (A), (B) or (C) NR4R5 is a nitrogen-containing heterocyclic ring; R6 is C1-3 alkyl; and R7 and R8, which are the same or different, are each H, C1-3 alkyl, halogen, CF3 or CN, provided that both are not H; or a pharmaceutically-acceptable salt thereof

Abstract: Compounds of formula (I) are useful therapeutic agents, by virtue of having MMP and TNF inhibitory activity.

Abstract: Substantially single-enantiomer(−)-tramadol, and its metabolites and structural and/or functional analogues, are useful for the prevention and/or treatment of one or more symptoms selected from nausea, vomiting, dizziness, blurred vision, drowsiness, somnolence, hallucinations, respiratory depression, constipation and euphoria. In particular, substantially single enantiomer (−)-tramadol, and its o-desmethyl metabolite, have been found to be potent anti-emetics.