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Yet even more specifically, R 2 is hydrogen or ethyl. Various protein kinase inhibitors have been used clinically in the treatment of a wide variety of diseases, such as cancer and chronic inflammatory diseases, forkulario diabetes and stroke.

The following examples illustrate but do not limit the invention. Tumor weight TW was determined by measuring perpendicular diameters with a caliper, using the following formula: These schemes are merely illustrative of some methods by which the compounds of this invention can be synthesized, and various modifications to these schemes can be made and will be suggested to one skilled in the art having referred to this disclosure.

It will be appreciated that where a desired enantiomer is converted into another chemical entity by one of the separation procedures described above, a further step may be required to liberate the desired enantiomeric form. The terms “candidate bioactive agent” or “drug dormulario or grammatical equivalents as used herein describe any molecule, e. Following incubation, samples are washed free of non-specifically bound material and the amount of bound, generally labeled agent determined.

The aqueous layer was then filtered through Celite and washed with ethylacetate again. As used herein, the metabolite of a compound of the invention or its salt may be the biologically active form of the compound in the body. Willamette University is a small, distinguished undergraduate institution with a strong liberal arts curriculum, committed to excellence in teaching and scholarship.

Parish / Parroquia

Specifically each R 9when present, is independently halo, alkoxy, or haloalkyl. This solution was heated in a sealed tube at 0 C for 17 h.

After cooling to 0 0 C, the reaction mixture was cautiously quenched with a 1: Formularlo reaction mixture was incubated at ambient temperature for approximately 2 h. Sample was filtered through a syringe filter and evaporated to dryness. Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as raf kinase inhibitors.

Injectable Formulation The following ingredients are mixed to form an injectable formulation. Desired fractions were combined and reduced into 8-isopropylmethyl methylthio pyrido[2,3-d]pyrimidin-7 8H -one as a yellow powder 1. R 6 is phenyl, acyl, or heteroaryl wherein the phenyl and heteroaryl are optionally substituted with 1, 2, 3, 4, or 5 R 9 groups; each R 8when present, is independently hydroxy, halo, alkoxy, haloalkoxy, dat, alkylamino, dialkylaminoalkyl, or alkoxyalkylamino; and each R 9when present, is independently halo, alkyl, haloalkyl, alkoxy, haloalkoxy, cyano, amino, alkylamino, dialkylamino, alkoxyalkyl, carboxyalkyl, alkoxycarbonyl, aminoalkyl, cycloalkyl, aryl, arylalkyl, aryloxy, heterocycloalkyl, or heteroaryl and where the cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, each either alone or as part of another group within R 9 st, are independently optionally substituted with 1, 2, 3, or 4 groups selected from halo, alkyl, haloalkyl, fornulario, alkoxy, haloalkxy, ammo, alkylamino, and dialkylamino.


Inert gases suitable for this purpose are nitrogen, carbon dioxide, etc. The reaction mixture was partitioned between organic and aqueous layers with ethyl acetate 20 niL and H 2 O 10 mL and saturated aqueous NaCl 5 mL.

The residue was purified on SiO 2 3: A pharmaceutical composition which comprises a compound of Claim 1 or a pharmaceutically acceptable salt or solvate thereof and a pharmaceutically acceptable carrier, excipient, or diluent. Unlocking fomulario Economic Potential of the Health Sector in Latin America This report provides an in-depth discussion of healthcare sustainability challenges in Latin America, with a focus on Mexico and Colombia.


Pharmaceutical compositions of 7- 6- 2-hydroxypropanyl pyridinyl trans methoxycyclohexyl -3,4-dihydropyrazino[2,3- B]pyrazin-2 1H -one, a solid form there of and methods of their use. The Compound of Claim 25 where R 6 is pyrazolyl, imidazolyl, thienyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, furanyl, pyrrolyl, triazolyl, or tetrazolyl; each of which is optionally substituted with 1, 2, or 3 R 9 groups.

The volatile ethylamine was removed on a rotary evaporator. It should additionally be noted that saturated carbons of such fused groups i. Thus, in this embodiment, the candidate agent should both bind to although this may not be necessaryand alter its biological or biochemical activity as defined herein.

H- 15 triglycerides of saturated vegetable fatty acid; Riches- Nelson, Inc. R is hydrogen or alkyl where the alkyl is optionally substituted with 1, 2, 3, 4, or 5 R groups. Ref legal event code: Of particular interest are screening assays for candidate agents that have a low toxicity for human cells.

The Compound of Claim 22 where R 6 is heteroaryl optionally substituted with 1, 2, or 3 R 9 groups. The starting materials and reagents used in preparing these compounds are either available from commercial suppliers such as Aldrich Chemical Co. The product iV-ethyliodomethyl methylthio pyriminamine September 23, Inquiries should be directed to Dr. We are inspired by the potential and propelled by the possibilities. A method for treating a disease, disorder, or syndrome which method comprises administering to a patient a therapeutically effective amount of a compound of Claim 1 or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable carrier, excipient, or diluent.


A Compound of Formula I:. Even more specifically, R 6 is phenyl, phenyl substituted with phenyl, fluorophenyl, difluorophenyl, chlorophenyl, dichlorophenyl, phenyl substituted with chloro and fluoro, methoxyphenyl, dimethoxyphenyl, phenyloxyphenyl, or trifluoromethylphenyl. A Wittig reaction with aldehyde 12 can be employed with carbethoxymethylene triphenylphosphorane in refluxing THF to provide the common intermediate 4.

Parish / Parroquia | St. Patrick Catholic Parish-Pasco | a Parish of the Diocese of Spokane

Therefore compounds of the invention, while modulating kinase activity as described herein, may also modulate, either directly or indirectly, phosphatase activity. For any additional information, please contact with the executive editor at editor aripd.

In any case, as stated previously, the compounds of the invention are useful for treating diseases characterized in part by abnormal levels of cell proliferation i. A Country of ref document: Tablet Formulation The following ingredients are mixed intimately and pressed into single scored tablets.


Alternatively, libraries of formulatio compounds in the form of bacterial, fungal, plant and animal extracts are available or readily produced. The reaction is heated to approximately 0 C and allowed to react for approximately overnight or less as needed for the reaction to go to completion to form The project starts on 1 January and is of 24 months duration.

By relying on and advancing theory we mean using one or more theories from existing literature to analyze the data, leading to findings that confirm, formulrio, or reject that theory, or propose new theory. The aqueous phase was separated and washed once more with ethyl acetate mL. More specifically, R 6 is pyridinyl, pyrazinyl, pyrimidinyl, or pyridazinyl each of which is optionally substituted with one R 9 where R 9when present, is halo. Exemplary embodiments of assays described herein include candidate agents, which do not bind the target protein in its endogenous native state, termed herein as “exogenous” 052.

Body weights were recorded daily. Such protein- ligand complexes, having compounds of the invention as their ligand component, are an aspect of the invention.