Abstract: Antibiotic compositions comprising an equilibrium mixture of azalide isomers, water, and one or more acids, and methods for preparing such compositions, are disclosed. The antibiotic compositions can be advantageously stabilized by adding one or more water-miscible co-solvents. In a preferred embodiment, the one or more co-solvents is propylene glycol.

Abstract: The invention features transgenic non-human mammals and transgenic cells expressing a radical fringe transgene comprising a radical fringe coding sequence, wherein expression of said coding sequence in said mammal is driven by an operably linked regulatory sequence that directs inducible and keratinocyte-specific expression, and wherein said mammal exhibits accelerated wound healing and/or increased keratinocyte proliferation following the induction of transgene expression. The invention also features polynucleotide and amino acid sequences for human radical fringe, methods of treating psoriasis and promoting wound healing by administering a modulator of radical fringe polypeptide activity, and methods of identifying modulators of radical fringe activity.

Abstract: This invention relates to methods and pharmaceutical compositions useful in the treatment of conditions that are responsive to the elevation of testosterone levels in the body and the use of estrogen agonists/antagonists for the manufacture of medicaments for the treatment of conditions that are responsive to the elevation of testosterone levels in the body. The compositions are comprised of an estrogen agonist/antagonist and a pharmaceutically acceptable vehicle, carrier or diluent. These compositions are effective in treating male subject sexual dysfunction and timidity in female subjects including post-menopausal women and are effective in increasing libido in female subjects including post-menopausal women. In the case of male subject sexual dysfunction, the compositions may also include a compound which is an elevator of cyclic guanosine 3′,5′-monophosphate (cGMP).

Abstract: The present invention relates to polynucleotide molecules comprising nucleotide sequences encoding an aveC gene product, which polynucleotide molecules can be used to alter the ratio or amount of class 2:1 avermectins produced in fermentation cultures of S. avermitilis. The present invention further relates to vectors, host cells, and mutant strains of S. avermitilis in which the aveC gene has been inactivated, or mutated so as to change the ratio or amount of class 2:1 avermectins produced.

Abstract: This invention is directed to methods, pharmaceutical compositions and kits comprising an aldose reductase inhibitor (ARI), a prodrug thereof or a pharmaceutically acceptable salt of said ARI or said prodrug and a selective COX-2 inhibitor, a prodrug thereof or a pharmaceutically acceptable salt of said selective COX-2 inhibitor or said prodrug. This invention further relates to methods of using those pharmaceutical compositions for the treatment of diabetic complications such as diabetic neuropathy, diabetic nephropathy, diabetic retinopathy and diabetic cardiomyopathy.

Abstract: Compounds of the formula wherein X is NR4R5, Y is selected from C1-C6 alkyl; alkoxyalkyl, C2-C6 alkenyl; C2-C6 alkynyl, alkoxy, aryl, or heteroaryl, or NR4R5, and R3 is selected from optionally substituted aryl or heteroaryl, optionally substituted, are neuropeptide antagonists and are effective in treating feeding disorders, cardiovascular diseases and other physiological disorders related to an excess of neuropeptide Y.

Abstract: The invention provides a method for treating certain neurologic and psychiatric disorders in mammals, including humans, comprising administration of a selective PDE10 inhbitor. In particular, the invention relates to treatment of mood, movement, and anxiety disorders; psychosis; drug, for example alcohol, addiction; disorders having as a symptom deficient cognition; and neurodegenerative disorders and conditions. The invention furthermore provides the use of papaverine as a selective inhibitor of PDE10. The invention also provides assays for identifying chemical compounds that have activity as selective PDE10 inhibitors.

Abstract: Compounds of formula (I), their salts and solvates, wherein the substituents are as described herein, are FKBP inhibitors.

Abstract: The present invention relates to polynucleotide molecules comprising nucleotide sequences encoding the aveC gene product, which polynucleotide molecules can be used to alter the ratio or amount of class 2:1 avermectins produced in fermentation cultures of Streptomyces avermitilis. The present invention further relates to vectors, host cells, and mutant strains of Streptomyces avermitilis in which the aveC gene has been inactivated, or mutated so as to change the ratio or amount of class 2:1 avermectins produced.

Abstract: A compound of the formula wherein R1-R9 and Ar are as defined above, useful in the treatment of a condition selected from the group consisting of arthritis, cancer, tissue ulceration, restenosis, periodontal disease, epidemrolysis bullosa, scleritis and other disease characterized by matrix metalloproteinase activity, as well as AIDS, sepsis, septic shock and other diseases involving the production of TNF.

Abstract: Compounds of formula (I), their salts and prodrugs thereof, where the substituents are as defined herein are disclosed as opiate binding agents useful in the treatment of opiate-mediated conditions. Also described are processes for making such substances.

Abstract: This invention relates to a series of substituted aromatic ethers of the formula I 1

Abstract: This invention relates to a series of substituted benzophenone and sulfone compounds of the formula I wherein ring A, Z, Y, R and X are defined as in the specification, that exhibit activity as glycine transport inhibitors, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, and their use for the enhancement of cognition and the treatment of the positive and negative symptoms of schizophrenia and other psychoses in mammals, including humans.

Abstract: The present invention relates to compounds of the formula wherein R1, R2, R3, R4, R5, R6, X and Y are defined as in the specification, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the invention are useful in the treatment or alleviation of inflammation and other inflammation associated disorders, such as arthritis, colon cancer, and Alzheimer's disease in mammals, preferably humans, dogs, cats and livestock.

Abstract: The invention provides a compound of formula (I): and its pharmaceutically acceptable salts, wherein R is halo C2-C8 alkenyl or halo C2-C8 alkynyl; R1 is hydrogen, halo or C1-C6 alkoxy; or R and R1, together with the two carbon atoms to which they are attached, form a C4-C6 cycloalkyl or a C4-C6 oxacycloalkyl ring wherein said ring may be optionally substituted by one or more substituents selected from the group consisting of halo, C1-C6 alkyl and halo C1-C6 alkyl; X is C1-C6 alkoxy, halo C1-C6 alkoxy, phenoxy or halo; and Ar is phenyl optionally substituted by halo. These compounds are useful in the treatment of a gastrointestinal disorder; a central nervous system (CNS) disorder; an inflammatory disease; emesis; urinary incontinence; pain; migraine; sunburn; diseases, disorders and adverse conditions caused by Heliobacter pylori; or angiogenesis especially CNS disorders in a mammalian subject, especially humans.

Abstract: Treating or preventing the early stages of degeneration of articular cartilage or subchondral bone in the affected joint of a mammal is accomplished by administering a chondroprotective compound of Formula (I): where A is hydroxy, (C1-C4)alkoxy, amino, hydroxy-amino, mono-(C1-C2)alkylamino, di-(C1-C2)alkylamino; X and Y are independently H or (C1-C2)alkyl; and n is 1 or 2; R6 is halogen, (C1-C3)alkyl, trifluoromethyl, or nitro; R9 is H; (C1-C2)alkyl; phenyl or phenyl-(C1-C2)alkyl, where phenyl is optionally mono-substituted by fluoro or chloro; —C(═O)—R, where R is (C1-C2)alkyl or phenyl, optionally mono-substituted by fluoro or chloro; or —C(═O)—O—R′, where R1 is (C1-C2)alkyl. This treatment ameliorates, diminishes, actively treats, reverses or prevents any injury, damage or loss of articular cartilage or subchondral bone subsequent to said early stage of said degeneration.

Abstract: The present invention also provides a general method to whereby mono-, bi-, or tricyclic heterocycles may be modified to obtain potent antagonists at the NPY1 receptor. The present invention provides novel, potent, non-peptidic antagonists of NPY receptors, particularly, the NPY1 receptors, designed from a selection of mono-, bi-, or tri-cyclic heterocyclic cores. This invention relates to novel compounds, compositions, and methods for the treatment of physiological disorders associated with an excess of neuropeptide Y. The novel compounds encompassed by the present invention are those of the formula I-XV.

Abstract: The invention provides a method for treating certain neurologic and psychiatric disorders in mammals, including humans, comprising administration of a selective PDE10 inhbitor. In particular, the invention relates to treatment of mood, movement, and anxiety disorders; psychosis; drug, for example alcohol, addiction; and disorders having as a symptom deficient cognition. The invention furthermore provides the use of papaverine as a selective inhibitor of PDE10.

Abstract: A pharmaceutical composition and method of modulating cholinergic function in a mammal comprising administration of a NRPA compound or a pharmaceutically acceptable salt thereof; and an anti-emetic/anti-nausea agent or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.

Abstract: The present invention relates to compounds of the formula I 1