- HETEROCYCLIC MODULATORS OF HIF ACTIVITY FOR TREATMENT OF DISEASE
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The present invention relates to compounds and methods which may be useful as inhibitors of HIF pathway activity for the treatment or prevention of cancer and other hypoxia-mediated diseases.
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Paragraph 0344; 0345
(2014/03/25)
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- PYRAZOLYL DERIVATIVES AS SYK INHIBITORS
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The present invention provides novel pyrazole derivatives of formula I which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis, and cancer.
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Page/Page column 130
(2014/01/09)
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- BENZOXAZINONE DERIVATIVES FOR THE TREATMENT OF GLYTL MEDIATED DISORDERS
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The present invention relates to benzoxazinone derivatives, processes for their preparation, pharmaceutical compositions and medicaments containing them and to their use in treating disorders mediated by GlyT1, including neurological and neuropsychiatric disorders, in particular psychoses, dementia or attention deficit disorder.
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Page/Page column 111
(2011/02/24)
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- BIS-PYRIDYLPYRIDONES AS MELANIN-CONCENTRATING HORMONE RECEPTOR 1 ANTAGONISTS
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The invention provides novel bis-pyridylpyridones which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), pharmaceutical compositions containing them, processes for their preparation, and their use in therapy and for the treatment of obesity and/or diabetes.
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Page/Page column 30
(2009/07/17)
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- Synthesis of methylene- and difluoromethylenephosphonate analogues of uridine-4-phosphate and 3-deazauridine-4-phosphate
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(Chemical Equation Presented) Cytidine triphosphate synthetase (CTPS) catalyzes the formation of cytidine triphosphate from glutamine, uridine-5′-triphosphate (UTP), and adenosine-5′-triphosphate. Inhibitors of CTPS are of interest because of their potential as therapeutic agents. One approach to potent enzyme inhibitors is to use analogues of high energy intermediates formed during the reaction. The CTPS reaction proceeds via the high energy intermediate UTP-4-phosphate (UTP-4-P). Four novel analogues of uridine-4-phosphate (U-4-P) and 3-deazauridine-4-phosphate (3-deazaU-4-P) were synthesized in which the labile phosphate ester oxygen was replaced with a methylene and difluoromethylene group. The methylene analogue of U-4-P, compound 1, was prepared by a reaction of the sodium salt of tert-butyl diethylphosphonoacetate with protected, 4-O-activated uridine followed by acetate deprotection and decarboxylation. It was found that this compound undergoes relatively facile dephosphonylation presumably via a metaphosphate intermediate. The difluoromethylene derivative, compound 2, was prepared by electrophilic fluorination of protected 1. This compound was stable and did not undergo dephosphonylation. Synthesis of the methylene analogue of 3-deazaU-4-P, compound 3, was achieved by ribosylation of protected 4-(phosphonomethyl)-2- hydroxypyridine. Electrophilic fluorination was also employed in the preparation of protected 4-(phospho-nodifluoromethyl)-2-hydroxypyridine which was used as the key building block in the synthesis of difluoro derivative 4. These compounds represent the first examples of a nucleoside in which the base has been chemically modified with a methylene or difluormethylenephosphonate group.
- Taylor, Scott D.,Mirzaei, Farzad,Sharifi, Ali,Bearne, Stephen L.
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p. 9420 - 9430
(2007/10/03)
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- Method of treating cancer
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The present invention relates to methods of treating cancer using a combination of a compound which is a PSA conjugate and a compound which is a inhibitor of prenyl-protein transferase, which methods comprise administering to said mammal, either sequentially in any order or simultaneously, amounts of at least two therapeutic agents selected from a group consisting of a compound which is a PSA conjugate and a compound which is a inhibitor of prenyl-protein transferase. The invention also relates to methods of preparing such compositions.
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- Inhibitors of farnesyl-protein transferase
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The present invention is directed to compounds which inhibit farnesyl-protein transferase (FTase) and the farnesylation of the oncogene protein Ras. The invention is further directed to chemotherapeutic compositions containing the compounds of this invent
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