Abstract: The present invention relates to compounds useful in the treatment of cancer or other proliferative diseases represented by the formula wherein: R1, R2, R3, R4, R5 are hydrogen or lower alkyl; R6 is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, or heterocyclo; X is hydrogen and Y is hydroxy, or X and Y taken together represent a carbon-carbon bond; and pharmaceutically acceptable salts, solvates, or hydrates thereof. Also included are therapeutic compositions containing the compounds represented by formula I as active ingredients, alone or in combination with other therapeutic agents useful in the treatment of cancer or other proliferative diseases.

Abstract: The present invention relates generally to novel nucleotide and amino acid sequences, and more particularly to novel human acetyl CoA carboxylase 2 (ACC2) and rat ACC2 sequences. The sequences provided herein can be expressed in a recombinant format. Methods of isolating the ACC2 sequence are also provided, which can be employed to isolate any ACC sequence. The ACC2 sequences can be employed in therapeutic applications to diagnose or treat a condition associated with ACC2. The invention also relates to the identification of modulators of ACC activity using the recombinant human ACC2 enzyme as the screening target.

Abstract: Compounds having the formula, enantiomers, diastereomers, solvates and salts thereof, where R1, R2, R3, R4, A, X, and J are described herein, are inhibitors of calcium channel function, and are useful in treating calcium channel-dependent disorders, including hypertension.

Abstract: Sulfonamide lactams of the following formula wherein X, R1, R2, R3, R4, R4a, R5, R5a, R6, R6a, R7 and R8 are as described herein, are provided which inhibitors of Factor Xa and are useful as anticoagulants in the treatment of cardiovascular diseases associated with thromboses.

Abstract: Novel heterocyclic aromatic compounds are provided that are useful in stimulating endogenous production or release of growth hormone, said compounds having the general structure of formula I wherein R1, R1?, R2, R3, R4, Xa, Y, Z and n are as described herein. The compounds provided herein are useful in treating obesity, osteoporosis (improving bone density) and in improving muscle mass and muscle strength.

Abstract: The present invention relates to substituted dihydropyrimidine inhibitors of calcium channel function having formula I where A, a, J, R1, R2 R3, R4, and R5, are defined herein; pharmaceutical compositions comprising said compounds; and methods of treating calcium channel-dependent disorders, including hypertension.

Abstract: Compounds having the formula (I), and pharmaceutically-acceptable salts, hydrates, or prodrugs thereof, are useful as serine protease inhibitors, wherein X is —OH, —O(alkyl), —O(aryl), —O(arylalkyl), —NR5(aryl), or —NR5(arylalkyl); W is hydrogen or —(CR7R8)q—W1; W1 is hydrogen or a bond with R6; Z is a 5-membered heteroaryl group, a five to six membered heterocyclo or cycloalkyl group, a 9 to 10 membered bicyclic aryl or heteroaryl, or a six membered aryl or heteroaryl, and R1, R2, R3, R5, R6, R7, and R16 are as defined in the specification.

Abstract: The present invention provides process useful for the preparation of intermediates which are useful in the preparation of amino acids useful in preparing peptide receptor modulators, for example agonists or partial agonists of such peptide receptors. Such peptide receptor modulators include, for example glucagon like peptide-1 receptor modulators which are useful for the amelioration of the diabetic condition.

Abstract: The present application describes linear chain substituted monocyclic and bicyclic compounds and derivatives thereof of Formula I: P4-P-M-M4I or pharmaceutically acceptable salt forms thereof, P-M are rings substituted by a linear group. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

Abstract: The present application describes cyclic diamino compounds, derivatives thereof, and pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of factor Xa.

Abstract: Acyl guanidine compounds of the following Formula wherein R1, R2, R3, R4 and L are described herein, and pharmaceutical compositions thereof, are useful in treating leukocyte activation-associated disorders.

Abstract: Fused heterocylic compounds of the following Formula wherein R1, R2, R5, Z, J1 and J2 are described herein which are useful in treating leukocyte activation-associated disorders.

Abstract: Prodrugs of glycogen phosphorylase inhibiting compounds are provided which are useful in treating diabetes, having the formula I G(—O2CR?)m(—OH)n(—O2C(CH2)pCH3)qI wherein G is a C3 to C5 branched or straight carbon chain and (—O2CR?), (—OH) and (—O2C(CH2)pCH3) are attached to any available carbon atom along G; —O2CR? is a fragment of a compound of formula Ib where W is a bicyclic heteroaryl; m, n, p, q, X, Y, Z, R1 and R2 are as defined herein, as exemplified by Further provided are pharmaceutical compositions and methods for treating diabetes and related diseases employing the above compounds above, either alone or in combination with another therapeutic agent.

Abstract: The present invention provides soluble CTLA4 mutant molecules which bind with greater avidity to the CD80 and/or CD86 antigen than wild type CTLA4 or non-mutated CTLA4Ig. The soluble CTLA4 molecules have a first amino acid sequence comprising the extracellular domain of CTLA4, where certain amino acid residues within the S25-R33 region and M97-G107 region are mutated. The mutant molecules of the invention may also include a second amino acid sequence which increases the solubility of the mutant molecule.

Abstract: Pyrimidine phosphodiesterase 7 (PDE 7) inhibitors of the following formula wherein R1, R2, Z, J and L are described herein, and analogs thereof are provided which are useful in treating T-cell mediated diseases.

Abstract: The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase enzymes thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases which can be treated by inhibiting tyrosine kinase enzymes.

Abstract: The present invention provides a reactor for the gas-phase reaction of commercially available gases in the presence of an inert carrier gas to form product gas. The reactor has a streamlined, compact configuration and at least one solids collection and removal system downstream of the reactor, where solids are efficiently removed from the product gas stream, leaving high purity product gas. The removal system allows for a simple reactor design, which is easy to clean and operates continuously over longer periods of time.

Abstract: Compounds having the formula (I), G is a novel side chain selected from C2-6alkenyl, A3-aryl, —OR18, heteroaryl, A1-cyano, A2—OR17, A1—C(?O)R18, A1—CO2R18, A1—C(?O)NR18R19, A1—OC(?O)R18, A1—NR18C(?O)R19, A1—OC(?O)NR18R19, A1—NR18CO2R19, A1—NR18SO2R17, A1—SO2R17, A1—NR20C(?O)NR18R19, and A1—SR18; or when y is 0 or when W is not NHR22, G may be A1-heterocyclo, wherein A1 is a bond, C1-6alkylene or C2-alkenylene, A2 is C1-6alkylene or C2-6alkenylene, and A3 is C2-6alkenylene; W is selected from —NR21R22, —OR23, —NR21C(?O)R24, —NR21CO2R24, amidino, guanidino, or a heteroaryl, heterocyclo or C3-7cycloalkyl as defined in the specification, and X and R1 through R24 are as defined in the specification, are effective as modulators of melanocortin-receptors, particularly MC-1R and MC-4R.

Abstract: There are provided in accordance with the present invention two crystalline polymorphs, designated Form A and Form B, respectively, as well as mixtures thereof, of an epothilone analog represented by the formula Also provided are methods of forming the novel polymorphs, therapeutic methods utilizing them and pharmaceutical dosage forms containing them.

Abstract: The present invention relates to a process for the preparation of epothilone analogs by initially forming novel ring-opened epothilones and carrying out a macrolactamization reaction thereon. The subject process is amenable to being carried out in a single reaction vessel without isolation of the intermediate compound and provides at least about a three-fold increase in yield over prior processes for preparing the desired epothilone analogs.