- Design and Synthesis of Potent and Selective PIM Kinase Inhibitors by Targeting Unique Structure of ATP-Binding Pocket
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In the development of kinase inhibitors, one of the major concerns is selectivity. An effective strategy to achieve high selectivity is to utilize structural differences among kinases to inform inhibitor design. Here, we set out to improve the PIM (proviral integration site for Moloney murine leukemia virus) kinase-inhibitory selectivity of our previously reported 7-azaindole derivative 2, which has promising ADMET properties, by targeting a unique bulge in the ATP-binding pocket. 6-Substituted 7-azaindoles, especially the 6-chlorinated derivatives, proved to be potent and selective PIM kinase inhibitors and appear to be promising lead compounds for future drug discovery.
- Nakano, Hirofumi,Hasegawa, Tsukasa,Kojima, Hirotatsu,Okabe, Takayoshi,Nagano, Tetsuo
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- ANTICANCER AGENT
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An anticancer agent comprising a compound represented by the formula (I) [R1 represents hydrogen atom, hydroxyl group, a C1-6alkoxy group and the like; R2 and R3 represents hydrogen atom, a halogen atom, a C1-6alkyl group and the like; R4 represents hydrogen atom, a C1-6alkyl group, a C1-6alkylsulfonyl group and the like; R5 represents hydrogen atom or a substituent; .... represents a single bond or a double bond; R6 and R7 represents hydrogen atom, a C1-6alkyl group and the like; R8 represents hydrogen atom, a C1-6alkyl group and the like; A represents -O-, -S-, or - CH2-; D represents -C= or -N=; X represents methylene group, -O-, or -CO-; Q represents -N= or -C(R8)=; and Y represents a heterocyclic group or amino group], which shows a superior inhibitory activity against pim-1 kinase.
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- NEW IMIDAZOLONE DERIVATIVES, PREPARATION THEREOF AS DRUGS, PHARMACEUTICAL COMPOSITIONS, AND USE THEREOF AS PROTEIN KINASE INHIBITORS, IN PARTICULAR CDC7
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The present invention relates to imidazolone derivatives of formula (I) to methods of preparing such derivatives, intermediates thereto, pharmaceutical compositions comprising such derivatives, and methods of inhibiting protein kinase, and methods of treatment comprising administration of such derivatives.
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(2009/10/17)
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- Azaindole derivatives, process for their preparation, and their use as antitumor agents
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Novel 1H-pyrrolo[2,3-b]pyridines which are represented by formula (I): wherein R is a hydrogen or halogen atom or a group selected from —CN, —OH, —OCOR4, —(CH2)nNH2, —(CH2)nNHR4, —(CH2)nNHCOR4, —(CH2)nNHCONR4R5, —(CH2)nNHCOOR4, or —(CH2)nNHSO2R4, wherein n is either 0 or 1, R4and R5are as described in the specification; R1is hydrogen or an optionally substituted alkyl group; R2is an optionally substituted group selected from alkyl or aryl; R3is hydrogen or a group selected from —CONR4R5, —COOR4, —CONHOR4, —SO2NHR4, alkylsulphonylaminocarbonyl or perfluorinated alkylsulphonylaminocarbonyl; or a pharmaceutically acceptable salt thereof, are disclosed. These compounds are useful for treating cell proliferative disorders associated with an altered cell dependent kinase activity.
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