Abstract: The present invention relates to the synthesis of a new lass of indeno[1,2-c]pyrazol-4-ones of formula (I): that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk1-9 and their regulatory subunits know as cyclins A-H. This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

Abstract: The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor. In the process, for example, cyclopropane carboxaldehyde is alkylated to form 1,1,1-trichloro-2-cyclopropyl-ethanol; which in turn is hydroxy protected to form 1,1,1-trichloro-2-cyclopropylethyltosylate; which in turn undergoes elimination to form cyclopropyl acetylene. This improvement provides for high conversion of inexpensive, readily available starting materials into cyclopropylacetylene, high overall yields and can be conducted on an industrial scale.

Abstract: This invention relates to macrocyclic molecules which inhibit metalloproteinases, including aggrecanase, and the production of tumor necrosis factor (TNF). In particular, the compounds are inhibitors of metalloproteinases involved in tissue degradation and inhibitors of the release of tumor necrosis factor. The present invention also relates to pharmaceutical compositions comprising such compounds and to methods of using these compounds for the treatment of inflammatory diseases.

Abstract: The present application describes nitrogen containing heteroaromatics with ortho-substituted P1's and derivatives thereof of formula I: or pharmaceutically acceptable salt or prodrug forms thereof, wherein J is N or NH and D is substituted ortho to G on E and may be CH2NH2, which are useful as inhibitors of factor Xa.

Abstract: Corticotropin releasing factor (CRF) antagonists of formula I: and their use in treating anxiety, depression, and other psychiatric, neurological disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress.

Abstract: The present application describes novel substituted aryl hydroxamic acids of formula I: or pharmaceutically acceptable salt forms thereof, wherein ring A is a 5-8 membered ring containing from 0-2 heteroatoms selected from N, 0, and S, which are useful as metalloprotease inhibitors.

Abstract: The present invention relates generally to cyclic carbamates and isoxazolidines or Formula (I) or their pharmaceutically acceptable salts thereof, which are useful as antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds for the inhibition of platelet aggregation, as thrombolytics, and/or for the treatment of thromboembolic disorders.

Abstract: This invention relates generally to quinolin-2(1H)-ones and derivatives thereof of Formula (I): or stereoisomeric forms, stereoisomeric mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, pharmaceutical compositions and diagnostic kits comprising the same, methods of using the same for treating viral infection or as assay standards or reagents, and intermediates and processes for making the same.

Abstract: The invention relates to a method of treating neurological disorders associated with neurotransmitter deficit in a mammal comprising administering to the mammal a therapeutically effective amount of a combination of: (i) at least one neurotransmitter release enhancer, and (ii) at least one acetylcholinesterase inhibitor. The invention also relates to compositions and kits containing the same.

Abstract: The present invention relates to an apparatus for holding a probe and a method for using the same. The apparatus comprises a body portion having a longitudinal bore and a membrane holder positioned over a first end of the body portion. The membrane holder defines an opening which is covered by a membrane. A receptacle for receiving the probe is rotatably positioned within the longitudinal bore of the body portion at a second end of the body portion. The membrane, membrane holder, body portion, receptacle, and probe define a sealed chamber for containing a contacting medium.

Abstract: Novel compounds and pharmaceutical compositions thereof, and methods of using same in treating anxiety, depression, and other psychiatric and neurological disorders. The novel compounds provided by this invention are those of the following formulae: wherein R1, R13, X, Y, Z, G and Q are as defined herein.

Abstract: Targeted ultrasound contrast agents are described. The contrast agents are porous particles of an inorganic material containing an entrapped gas or liquid and having an average particle diameter of about 0.05 to 500 microns. The outer surfaces of the particles incorporate a targeting ligand to target delivery of the contrast agent.

Abstract: This invention relates to novel radiopharmaceuticals comprised of highly functionalized pyridine ligated technetium-99m labeled HYNIC-biomolecules that selectively localize at sites of disease and thus allow an image to be obtained of the loci using gamma scintigraphy. The invention also provides methods of use of the radiopharmaceuticals as imaging agents for the diagnosis of cardiovascular disorders such as thromboembolic disease or atherosclerosis, infectious disease and cancer.

Abstract: The present invention relates to processes for the conversion of nitrites to amidines in the preparation of compounds which are antagonists of the platelet glycoprotein IIb/IIIa fibrinogen receptor complex. The compounds described herein are potent thrombolytics and useful for the inhibition of platelet aggregation in the treatment of thromboembolic disorders.

Abstract: Corticotropin releasing factor (CRF) antagonists of Formula (I): and their use in treating psychiatric disorders and neurological diseases, anxiety-related disorders, post-traumatic stress disorder, supranuclear palsy and feeding disorders as well as treatment of immunological, cardiovascular or heart-related diseases and colonic hypersensitivity associated with psychopathological disturbance and stress in mammals.

Abstract: Novel radiopharmaceutical compositions comprising, in combination with a pharmaceutically acceptable carrier, a radioactive salt of pyrophosphoric acid. Also provided are novel radiopharmaceutical compositions comprising, in combination with one or more polymeric resins, a radioactive salt of pyrophosphoric acid. The compositions and matrices are suitable, inter alia, for use in treatment methods involving brachytherapy.

Abstract: The present invention provides improved oral dosage form formulations of efavirenz that are useful in the inhibition of human immunodeficiency virus (HIV), the prevention or treatment of infection by HIV, and in the treatment of the resulting acquired immune deficiency syndrome (AIDS). In particular, the present invention relates to compressed tablets or capsules comprising efavirenz that contain one or more disintegrants that enhance the dissolution rate of the efavirenz in the gastrointestinal tract thereby improving the rate and extent of absorption of efavirenz in the body. The present invention also relates to the process of making such tablets or capsules.

Abstract: The present invention relates to compounds having pharmacological activity toward the 5-HT7 receptor. Pharmaceutical compositions and methods for their use in the treatment of CNS disorders are described.

Abstract: The present invention relates generally to novel methods for the synthesis of cyclopropylacetylene which is an essential reagent in the asymmetric synthesis of (S)-6-chloro-4-cyclopropylethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxazin-2-one; a useful human immunodeficiency virus (HIV) reverse transcriptase inhibitor.

Abstract: A palatable oral liquid pharmaceutical composition of benzoxazinone compounds useful as HIV reverse transcriptase inhibitors comprising the benzoxazinone active ingredient in a liquid vehicle comprising medium chain fatty acid triglycerides. Other formulating agents such as sweetening agents, lecithin suspending agents, etc. may be optionally added.