Abstract: Disclosed are compounds which are inhibitors of metalloproteases and which are effective in treating conditions characterized by excess activity of these enzymes. In particular, the compounds have a structure according to the following Formula (I): where R1, R2, R3, n, A, E, X, G, G?, M and Z have the meanings described in the specification and the claims, as well as optical isomers, diastereomers and enantiomers of Formula I, and pharmaceutically-acceptable salts, biohydrolyzable amides, esters, and imides thereof. Also described are pharmaceutical compositions comprising these compounds, and methods of treating metalloprotease-related maladies using the compounds or the pharmaceutical compositions.

Abstract: Screening methods for identifying compounds that regulate skeletal muscle atrophy or hypertrophy, regulate the activity or expression of the vasoactive intestinal peptide receptors (VPAC) or regulate expression of vasoactive intestinal peptide (VIP) or VIP analogs are provided. Methods for the prophylactic or therapeutic treatment of skeletal muscle atrophy utilizing VPAC as the target for intervention are described.

Abstract: Screening methods for identifying compounds that bind to or activate corticotropin releasing factor2 receptors (CRF2R) and regulate or potentially regulate skeletal muscle mass or function in vivo. Also disclosed are screening methods for identifying compounds that prolong or augment the activation of CRF2Rs or of CRF2R signal transduction pathways, increase CRF2R or increase CRF expression are provided. Pharmaceutical compositions comprising CRF2R agonists, antibodies to CRF2R and methods for increasing skeletal muscle mass or function or for the treatment of skeletal muscle atrophy using CRF2R as the target for intervention and methods for treatment of muscular dystrophies are described.

Abstract: Disclosed are cyclic peptide analogs that are MC-4 and/or MC-3 receptor ligands, the analogs having a structure according to Formula (I): wherein B, X, E, Z, D, G, M′, W, R, R1, R1′, R11, m, n, p and q are as described in the specification. The peptide analogs are useful in treating diseases that are mediated by the MC-4 and/or the MC-3 receptor. As such, the invention is directed to methods of treating body weight disorders, such as obesity, anorexia, and cachexia. The invention also relates to the treatment of CNS depression, behavior-related disorders, memory-related disorders, cardiovascular function, inflammation, sepsis, septic shock, cardiogenic shock, hypovolemic shock, sexual dysfunction, erectile dysfunction, muscle atrophy, diseases associated with nerve growth and repair, and intrauterine fetal growth. Also disclosed are pharmaceutical compositions comprising the peptide analogs of Formula (I).

Abstract: The present invention is directed to a novel enteric-coated oral dosage form of a risedronate active ingredient comprised of a safe and effective amount of a pharmaceutical compostion which is comprised of a risedronate active ingredient and pharmaceutically-acceptable excipients. Said dosage forms prohibit the exposure of the risedronate active ingredient to the epithelial and mucosal tissues of the buccal cavity, pharynx, esophagus, and stomach and thereby protects said tissues from erosion, ulceration or other like irritation. Accordingly, the said dosage forms effect the delivery to the lower intestinal tract of said human or other mammal of a safe and effective amount of the risedronate active ingredient, and substantially alleviate the esophagitis or esophageal irritation which sometimes accompanies the oral administration of risedronate active ingredients.

Abstract: A novel oral dosage to be delivered to the stomach comprising a safe and effective amount of an active ingredient selected from the group consisting of emepronium bromidebromide, doxycycline, and other tetracyclines/antibiotics, iron preparations, quinidine, nonsteroidal anti-inflammatory drugs, alprenolol, ascorbic acid, captopril, theophylline, zidovoudine (AZT), bisphosphonates and mixtures thereof and pharmaceutically-acceptable excipients, wherein said oral dosage form is a generally oval form and film coated to facilitate rapid esophageal transit and avoid irritation in the mouth, buccal cavity, pharynx, and esophagus.

Abstract: The present invention relates to a novel process for making geminal bisphosphonates. The process provides for bisphosphorylation using phosphorus trihalide, phosphorous acid as a reactant/solvent, and a base as an acid acceptor/solvent.

Abstract: The subject invention involves compounds having the structure: wherein the C&agr;—N&bgr;, C5-C6, and C6-C7 bonds are each single or double bonds, except that both C5-C6, and C6-C7 are double bonds; R1 is selected from hydrogen, alkyl, aryl, and heterocycle; R2-R15 are independently selected from hydrogen and other substituents; and pharmaceutically-acceptable forms thereof. The subject invention also involves pharmaceutical compositions containing such compounds, and methods for treating or preventing diseases and disorders using such compounds.

Abstract: The present invention relates to a dispensing device (1) for a fluid (10), the dispensing device (1) comprising a reservoir (11), a shaft (12), a back seal (13), a damper (14), a piston (151) and a one-way valve (16), the back seal (13) sealing a first end of the reservoir and being displaceable along the shaft, the valve being on the second end of the reservoir, the piston being fixed to one end of the shaft, the piston being located between the valve and the damper, the damper being also fixed to the shaft, the damper being located between the piston and the back seal, whereby the piston has an opened position (151) and a closed position (152), the open position allowing fluid communication between the valve and the pat of the reservoir between the piston and the back seal, the displacement of the piston between the opened and the closed position being induced by a displacement of the shaft along its own axis, the pressure in the area comprised between the valve and the piston reducing when the piston is mo

Abstract: A process for making 1,3-disubstituted-4-oxocyclic ureas of general formula (I): wherein R1, R2, and R3 are independently selected from the group consisting of nil, Cl, F, Br, NH2, NO2, COOH, CH3SO2NH, SO3H, OH, alkoxy, alkyl, alkoxycarbon hydroxyalkyl, carboxyalkyl, and acyloxy; R4 is selected from the group consisting of a substituted or unsubstituted alkyl, alkenyl alkynyl, alkylacyl, and heteroalkyl; and A is a substituted or unsubstituted, saturated or unsaturated, straight-chain or branched alkyl or alkenyl amino group comprised of 1-7 carbon atoms; or A is a substituted or unsubstituted, saturated or unsaturated heterocycle having 5, 6, or 7 members containing at least one nitrogen, and R4 is attached to this nitrogen; wherein said 1,3-disubstituted tuted-4-oxocyclic urea is made without isolation of intermediates and comprising the steps: (Ia) reacting a l-substituted-4-oxocyclic urea with a carbon chain containing at least two leaving groups in the presence of a mild base and a solv

Abstract: A process for making 1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]amino]-3-[4-(4-methyl-1-piperizinyl)butyl]-2,4-imidazolidinedione having the formula: is disclosed. The process circumvents the use of sodium hydride and isolation of reaction intermediates following the initial coupling of the hydantoin intermediate and 4-N-methylpiperizine.

Abstract: The present invention discloses 3-pyridyl-1-hydroxyethylidene-1,1-bisphosphonic acid sodium hemipentahydrate and monohydrate, methods of preparing the hemipentahydrate or monohydrate through control of the nucleation temperature and rate of crystallization and pharmaceutical compositions containing one or both of the hydrate forms.

Abstract: This invention involves compounds having the following structure: as described in the Claims; and enantiomers, optical isomers, stereoisomers, diastereomers, tautomers, addition salts, biohydrolyzable amides and esters thereof, as well as pharmaceutical compositions comprising such novel compounds. The invention also relates to the use of such compounds for preventing or treating disorders modulated by alpha-2 adrenoceptors.

Abstract: The invention provides novel Prostaglandin F analogs. In particular, the present invention is directed to compounds having a structure according to the following formula: wherein R1, R2, X, Y, V, a, b, W, and Z are defined below. This invention also includes optical isomers, diastereomers and enantiomers of the formula above, and pharmaceutically—acceptable salts, biohydrolyzable amides, esters, and imides thereof. The compounds of the present invention are useful for the treatment of a variety of diseases and conditions, such as bone disorders and glaucoma. Accordingly, the invention further provides pharmaceutical compositions comprising these compounds. The invention still further provides methods of treatment for bone disorders and glaucoma using these compounds or the compositions containing them.

Abstract: A novel oral dosage to be delivered to the stomach comprising a safe and effective amount of an active ingredient selected from the group consisting of emepronium bromidebromide, doxycycline, and other tetracyclines/antibiotics, iron preparations, quinidine, nonsteroidal anti-inflammatory drugs, alprenolol, ascorbic acid, captopril, theophylline, zidovoudine (AZT), bisphosphonates and mixtures thereof and pharmaceutically-acceptable excipients, wherein said oral dosage form is a generally oval form and film coated to facilitate rapid esophageal transit and avoid irritation in the mouth, buccal cavity, pharynx, and esophagus.

Abstract: The present invention relates to novel methods of increasing bone volume comprising the administration of a non-naturally-occurring selective FP agonist to a subject in need of such treatment. This invention further relates to a method of treating or preventing bone disorders comprising the administration of a non-naturally-occurring selective FP agonist to a subject in need of such treatment.

Abstract: A compound having structure (1) wherein (a) X is selected from the group consisting of O, S, SO, or SO.sub.2 ; (b) each Y is independently hydrogen or straight, branched or cyclic alkanyl having from 1 to about 4 carbon atoms, or the two Y's are bonded to form an alkanyl ring having from 3 to about 7 carbon atoms; (c) Z is branched or cyclic alkyl having from 3 to about 10 atoms other than hydrogen; (d) W is O or S; and (e) R is straight, branched or cyclic alkyl or aryl, saturated or mono- or di-unsaturated with double or triple bonds, R having from 1 to about 15 atoms other than hydrogen; pharmaceutical compositions comprising such compounds, and methods of treating inflammation or pain using such compounds.

Abstract: A compound having the structure: ##STR1## wherein (a) n is from 1 to about 3;(b) X is selected from the group consisting of O, S, SO, or SO.sub.2 ;(c) Y is independently hydrogen or straight, branched or cyclic alkyl having from 1 to about 4 carbon atoms, or the Y's are bonded together to form an alkanyl ring having from about 3 to about 7 atoms;(d) Z is hydrogen or straight, branched or cyclic alkyl having from 3 to about 10 atoms other than hydrogen;(e) W is O or S; and(f) Het is a heteroaryl group comprising one or more rings each ring containing from about 5 to about 6 atoms other than hydrogen and wherein the group contains at least one heteroatom selected from O, N, or S.pharmaceutical compositions comprising such compounds, and methods of treating inflammation or pain using such compounds.

Abstract: The present invention is directed to a novel enteric-coated oral dosage form of a risedronate active ingredient comprised of a safe and effective amount of a pharmaceutical compostion which is comprised of a risedronate active ingredient and pharmaceutically-acceptable excipients. Said dosage forms prohibit the exposure of the risedronate active ingredient to the epithelial and mucosal tissues of the buccal cavity, pharynx, esophagus, and stomach and thereby protects said tissues from erosion, ulceration or other like irritation. Accordingly, the said dosage forms effect the delivery to the lower intestinal tract of said human or other mammal of a safe and effective amount of the risedronate active ingredient, and substantially alleviate the esophagitis or esophageal irritation which sometimes accompanies the oral administration of risedronate active ingredients.

Abstract: The present invention provides a process for making 2-amino-2-imidazoline, guanidine, and 2-amino-3,4,5,6-tetrahydroyrimidine derivatives by preparing the corresponding activated 2-thio-subsituted-2-derivative in a two-step, one-pot procedure and by further reacting yields this isolated derivative with the appropriate amine or its salts in the presence of a proton source. The present process allows for the preparation of 2-amino-2-imidazolines, quanidines, and 2-amino-3,4,5,6-tetrahydropyrimidines under reaction conditions that eliminate the need for lengthy, costly, or multiple low yielding steps, and highly toxic reactants. This process allows for improved yields and product purity and provides additional synthetic flexibility.