- PYRAZINE KINASE INHIBITORS
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Provided are pyrazine compounds for inhibiting of Syk kinase, intermediates used in making such compounds, methods for their preparation, pharmaceutical compositions thereof, methods for inhibition Syk kinase activity, and methods for treating conditions mediated at least in part by Syk kinase activity.
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Paragraph 1140
(2013/06/04)
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- SUBSTITUTED CARBOXAMIDES
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This application relates to a substituted carboxamide compound of formula I, or a pharmaceutically acceptable salt thereof, as defined herein, a pharmaceutical composition thereof, and its use in treating pain.
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Page/Page column 26-27
(2008/12/08)
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- Methods for inhibiting protein kinases
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The present invention provides methods for inhibiting protein kinases selected from the group consisting of AKT, Checkpoint kinase, Aurora kinase, Pim-1 kinase, and tyrosine kinase using imidazo[1,2-a]pyrazine compounds and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with protein kinases using such compounds.
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Page/Page column 191-192
(2010/11/27)
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- Pyrimidine benzamide-based thrombopoietin receptor agonists
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A series of pyrimidine benzamide-based thrombopoietin receptor agonists is described. The lead molecule contains a 2-amino-5-unsubstituted thiazole, a group that has been associated with idiosyncratic toxicity. The potential for metabolic oxidation at C-5 of the thiazole, the likely source of toxic metabolites, was removed by substitution at C-5 or by replacing the thiazole with a thiadiazole. Potency in the series was improved by modifying the substituents on the pyrimidine and/or on the thiazole or thiadiazole pendant aryl ring. In vivo examination revealed that compounds from the series are not highly bioavailable. This is attributed to low solubility and poor permeability.
- Reiter, Lawrence A.,Subramanyam, Chakrapani,Mangual, Emilio J.,Jones, Christopher S.,Smeets, Marc I.,Brissette, William H.,McCurdy, Sandra P.,Lira, Paul D.,Linde, Robert G.,Li, Qifang,Zhang, Fangning,Antipas, Amy S.,Blumberg, Laura C.,Doty, Jonathan L.,Driscoll, James P.,Munchhof, Michael J.,Ripp, Sharon L.,Shavnya, Andrei,Shepard, Richard M.,Sperger, Diana,Thomasco, Lisa M.,Trevena, Kristen A.,Wolf-Gouveia, Lilli A.,Zhang, Liling
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p. 5447 - 5454
(2008/03/11)
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- Phototransposition chemistry of phenylisothiazoles and phenylthiazoles. 1. Interconversions in benzene solution
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Phenylthiazoles 1-3 and phenylisothiazoles 4-6 undergo phototransposition in benzene solvent mainly by P5, P6, and P7 permutation pathways. Phenylisothiazoles 5 and 6 also transpose via a P4 permutation process to yield phenylthiazoles 2 and 3 in less than 1% yield. In benzene saturated with D2O, 2-phenylthiazole (1) and 5-phenylisothiazole (6) each phototranspose to yield 4-deuterio-3-phenylisothiazole (4-D-4) and 4-phenylthiazole (2) without deuterium incorporation. Irradiation of 4-phenylthiazole (2) under these conditions results in rapid photodeuteration to yield 2-deuterio-4-phenylthiazole (2-D-2), which subsequently phototransposes to 5-deuterio-3-phenylisothiazole (5-D-3). These experimental results can be rationalized by a mechanism involving initial electrocyclic ring closure and sigmatropic shift of sulfur around the four sides of the azetine ring. Rearomatization of each bicyclic intermediate thus allows sulfur to insert into each position in the carbon-nitrogen sequence. As a consequence, these compounds divide into a tetrad in which isomers 1, 2,4, and 6 interconvert mainly via P5, P6, and P7 pathways and a dyad of two compounds in which 3 phototransposes to 5 via P5 and P7 pathways. Within the tetrad, BC-6, the bicyclic intermediate derived from 5-phenylisothiazoles (6), is postulated to undergo deuteration with simultaneous sigmatropic shift of sulfur when the reaction is carried out in benzene-D2O. This mechanistic view provides one coherent interpretation for the observed phototransposition and photodeuteration reactions.
- Pavlik, James W.,Tongcharoensirikul, Pakamas,Bird, Nigel P.,Day, A. Colin,Barltrop, John A.
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p. 2292 - 2300
(2007/10/02)
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- RING-TRANSFORMATION FROM ISOTHIAZOLE TO 1,2,4-THIADIAZOLE - POSSIBLE INTERMEDIACY OF ?-SULFURANE
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5-Amino-3-methyl- and 5-amino-3-phenylisothiazoles (3a and 3b) afforded 1:1 adducts with aromatic nitriles and imidates.On the basis of their spectral data and the structure of hydrolysis products, the adducts were identified as 3-substituted 5-(2-aminovinyl)-1,2,4-thiadiazole derivatives (2a-g), where ring transformation took place from isothiazole to 1,2,4-thiadiazole.
- Akiba, Kin-Ya,Noda, Akiko,Ohkata, Katsuo
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p. 111 - 118
(2007/10/02)
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