- 1,5,7-TRISUBSTITUTED ISOQUINOLINE DERIVATIVES, PREPARATION THEREOF, AND USE THEREOF IN MEDICINES
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The present disclosure relates to 1,5,7-trisubstituted isoquinoline derivatives, their preparation and pharmaceutical use. In particular, the present disclosure discloses a compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, and a preparation method and use thereof. The definitions of the groups in the formula can be found in the specification and claims.
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Paragraph 0259; 0261; 0265; 0268
(2020/08/30)
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- Lead Optimization toward Proof-of-Concept Tools for Huntington's Disease within a 4-(1 H -Pyrazol-4-yl)pyrimidine Class of Pan-JNK Inhibitors
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Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole. (Chemical Presented)
- Wityak, John,McGee, Kevin F.,Conlon, Michael P.,Song, Ren Hua,Duffy, Bryan C.,Clayton, Brent,Lynch, Michael,Wang, Gwen,Freeman, Emily,Haber, James,Kitchen, Douglas B.,Manning, David D.,Ismail, Jiffry,Khmelnitsky, Yuri,Michels, Peter,Webster, Jeff,Irigoyen, MacArena,Luche, Michele,Hultman, Monica,Bai, Mei,Kuok, Iokteng D.,Newell, Ryan,Lamers, Marieke,Leonard, Philip,Yates, Dawn,Matthews, Kim,Ongeri, Lynette,Clifton, Steve,Mead, Tania,Deupree, Susan,Wheelan, Pat,Lyons, Kathy,Wilson, Claire,Kiselyov, Alex,Toledo-Sherman, Leticia,Beconi, Maria,Mu?oz-Sanjuan, Ignacio,Bard, Jonathan,Dominguez, Celia
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p. 2967 - 2987
(2015/04/27)
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- Novel 2,4-Dianilinopyrimidine Derivatives, the Preparation Thereof, Their Use as Medicaments, Pharmaceutical Compositions and, in Particular, as IKK Inhibitors
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The disclosure relates to compounds of formula (I): wherein R1-R5, A and Y are as defined in the disclosure, to compositions comprising said compounds, and to processes for making and methods of using the same.
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Page/Page column 52
(2008/12/04)
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- Nicotinamide Derivatives
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The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof, wherein the substituents are as defined herein, compositions containing such compounds and the uses of such compounds for the treatment o
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Page/Page column 19
(2008/12/06)
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