Abstract: A method for identifying compounds that can be useful for producing analgesia is disclosed. In particular, the method involves providing preparation of a cell, that expresses an alpha1B adrenergic receptor, combining a test compound with the cell preparation, measuring the effect of the test compound on the alpha1B receptor activity, and evaluating the compound thus identified for analgesic activity.

Abstract: The present invention provides an aminopyrrole compound of the formula: a prodrug, individual isomer, a mixture of isomers or a pharmaceutically acceptable salt thereof, where R1, R2, Ar1 and Ar2 are those defined herein. The present invention also provides methods of using and preparing the aminopyrrole compounds of Formula I.

Abstract: The present invention provides compounds of the Formula I and II: wherein R1, R3, W, Z, X1, X2, Ar1, R8 and R9 are as defined herein, and methods and intermediates for their preparation and uses thereof.

Abstract: Human aggrecanase and polypeptides related thereto, as well as nucleic acid compositions encoding the same, are provided. The subject polypeptides and nucleic acid compositions find use in a variety of applications, including research, diagnostic, and therapeutic agent screening applications. Also provided are methods of inhibiting aggrecanase activity in a host and methods of treating disease conditions associated with aggrecanase activity, e.g. rheumatoid arthritis, osteo-arthritis, infectious arthritis, gouty arthritis, psoriatic arthritis, spondolysis, sports injury, joint trauma, pulmonary disease, fibrosis, and the like.

Abstract: Alkylamino-substituted dihydropyrimido[4,5-d]pyrimidinone derivatives are provided which are useful as inhibitors of p38, along with a process for their manufacture and pharmaceutical preparations containing them.

Abstract: This invention relates to compounds which are generally muscarinic M2/M3 receptor antagonists and which are represented by Formula I: wherein R1, R2, R3 and R4 are as defined in the specification, or individual isomers, racemic or non-racemic mixtures of isomers, or acceptable salts or solvates thereof. The invention further relates to pharmaceutical compositions containing such compounds and methods for their use and preparation as therapeutic drugs.

Abstract: The present invention relates to compounds of Formula (I) that are p-38 MAP kinase inhibitors, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.

Abstract: The invention relates to compounds of the general formula wherein (R1)n is independently from from each other halogen, lower alkyl or lower alkoxy; R2 is hydrogen, lower alkyl, lower halogen-alkyl, —(CH2)m—OH, —(CH2)m—NR2, —(CH2)mO-lower alkyl, —(CH2)m—C(O)—NR2, or is —(CH2)m-6-membered heteroaryl, optionally substituted by one or more lower alkoxy, —(CH2)m-5 or 6-membered not aromatic heterocyclyl, optionally substituted by hydroxy or lower alkyl; R is hydrogen or lower alkyl and may be the same or different in case of R2; n is 0, 1, or 2; m is 0, 1, 2, 3 or 4; and pharmaceutically acceptable acid addition salts thereof. These compounds have a good affinity to the NK-1 receptor and they are therefore suitable for the treatment of diseases, related to this receptor.

Abstract: This invention relates to IP receptor antagonists selected from the group of compounds represented by Formula I: where: R1 is a group represented by formula (A), (B) or (C);  and other substituents as defined in the specification, and their pharmaceutically acceptable salts or crystal forms thereof; and pharmaceutical compositions containing them; and methods and their use as therapeutic agents.

Abstract: The invention provides TCCV-1 or TCCV-2 from human, reagents related thereto including polynucleotides encoding TCCV-1 or TCCV-2, purified polypeptides, and specific antibodies. Methods of making and using these reagents, in particular, methods for screening compounds which modulate TCCV-1 or TCCV-2 activity are provided. Also provided are methods of diagnosis and kits.

Abstract: This invention provides methods of bone healing and fracture repair comprising administering to a patient in need thereof an effective amount of a polypeptide analog of parathyroid hormone related peptide (PTHrP) and salts thereof, wherein amino acid residues 22-31 form an amphipathic &agr;-helix. Systemic administration is a preferred mode of delivery.

Abstract: This invention relates to compounds which are IP receptor antagonists and which are represented by Formula (I): wherein G2 is a heteroaryl group containing one or two nitrogen atoms substituted with a carboxylic acid group, said heteroaryl ring containing one or two nitrogen atoms, and G1 is as defined in the specification; or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts or solvates thereof. The invention further relates to pharmaceutical compositions containing such compounds, methods for their use as therapeutic agents, and methods of preparation thereof.

Abstract: The present invention provides 3-desoxy vitamin D3 analog esters of the formula: and methods for use and preparation of the same, wherein the dotted line, R1, R2, R3, R4 and L are those defined herein.

Abstract: This invention relates to compounds which are generally alpha-1B adrenergic receptor antagonists and which are represented by Formula (I): wherein R′, R″, R1, R2, m, n, and A are as defined in the specification, or acceptable prodrug, salt or solvate thereof. The invention further relates to pharmaceutical compositions containing such compounds, methods for their use as therapeutic agents, and methods of preparation thereof.

Abstract: This invention relates to certain 2,4-substituted pyrrolidine derivatives that are CCR-3 receptor antagonists, pharmaceutical compositions containing them, methods for their use and methods for preparing these compounds.

Abstract: This invention provides processes for the preparation of a compound of Formula I: Y—C(═O)—C(R1)(R2)—CH2—S(O)nR3 wherein: Y is hydroxy or XONX, where each X is independently hydrogen, lower alkyl or lower acyl; R1 is hydrogen or lower alkyl; R2 is hydrogen, lower alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, or R1 and R2 together with the carbon atom to which they are attached form a cycloalkyl or heterocyclo group; R3 is aryl; and n is 0, 1 or 2. The invention also provides novel aryl haloalkyl sulfide intermediates useful for the preparation of compounds of Formula I and novel methods of preparing aryl alkyl sulfides.

Abstract: The present invention provides compounds of the formula: wherein R1, R3, and Ar1 are those defined herein, and R2 is —CR′R″—Ra (where R′ and R″ are hydrogen, hydroxyalkyl or alkyl with at least one being alkyl or hydroxyalkyl and Ra is hydroxyalkyl), Rx—S—Ry— (where Rx is alkyl and Ry is alkylene), alkoxy-substituted alkyl, heterocyclylalkyl or C4-C5 cycloalkyl, wherein each of the hydroxy group present in R2 can be independently Ra—C(═O)—O, RaRbN—C(═O)—O, or Ra—S(O)2—O—, wherein Ra and Rb are independently hydrogen, alkyl, aryl, or aralkyl, and methods for preparation and uses thereof.

Abstract: The invention provides a method of treatment for an animal having a disease state associated with a genitourinary disorder with a purinergic receptor modulator. Also provided, is a transgenic animal having a disrupted purinergic receptor gene. The invention further provides for a method of screening using the transgenic animal as a positive control.

Abstract: The present invention provides compounds of the formula: wherein R2 is substituted cycloalkyl, heterosubstituted cycloalkyl, heteroalkylsubstituted cycloalkyl, heterosubstituted cycloalkyl-alkyl, optionally substituted heterocyclyl, spiro-substituted cycloalkyl, aralkoxy, alkoxy, -alkylene-S(O)n-alkyl (wherein n is 1 or 2), or —SO2Ar2; and R1, R3, and Ar1 are those defined herein, and methods for preparation and uses thereof.

Abstract: This invention relates to compounds which are generally muscarinic M2/M3 receptor antagonists and which are represented by Formula I: wherein X, Y, and Z are O, S, or NR4, and the other substituents are as defined in the specification; and prodrugs, individual isomers, racemic or non-racemic mixtures of isomers, and pharmaceutically acceptable salts or solvates thereof. The invention further relates to pharmaceutical compositions containing such compounds and methods for their use as therapeutic agents.