65001-21-0Relevant articles and documents
PYRIDINESULFONAMIDE DERIVATIVES AS TRAP1 MODULATORS AND USES THEREOF
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Paragraph 00288; 00533-00534, (2021/09/26)
The present disclosure provides compounds of Formula (I): and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled compounds, and prodrugs thereof. The provided compounds may be tumor necrosis factor ("TNF") receptor associated protein 1 ("TRAP1") modulators (e.g., TRAP1 activators). The provided compounds may also rescue the activity in PTEN-induced kinase 1 ("PINK1") loss of function contexts. The provided compounds may also improve mitochondrial health, function, quality, quantity, and/or activity, and/or reduce the production of reactive oxygen species. The provided compounds may also refold or solubilize aggregated or misfolded proteins such as a-synuclein. The present disclosure also provides pharmaceutical compositions comprising the provided compounds; kits comprising the provided compounds or pharmaceutical compositions; and methods of using the provided compounds and pharmaceutical compositions (e.g., for treating a disease in a subject in need thereof).
SUBSTITUTED QUINOLINES AND METHODS FOR TREATING CANCER
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, (2018/05/24)
Substituted quinoline compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds to treat, prevent or ameliorate cancer are provided.
Identification of Purines and 7-Deazapurines as Potent and Selective Type i Inhibitors of Troponin I-Interacting Kinase (TNNI3K)
Lawhorn, Brian G.,Philp, Joanne,Zhao, Yongdong,Louer, Christopher,Hammond, Marlys,Cheung, Mui,Fries, Harvey,Graves, Alan P.,Shewchuk, Lisa,Wang, Liping,Cottom, Joshua E.,Qi, Hongwei,Zhao, Huizhen,Totoritis, Rachel,Zhang, Guofeng,Schwartz, Benjamin,Li, Hu,Sweitzer, Sharon,Holt, Dennis A.,Gatto, Gregory J.,Kallander, Lara S.
, p. 7431 - 7448 (2015/10/05)
A series of cardiac troponin I-interacting kinase (TNNI3K) inhibitors arising from 3-((9H-purin-6-yl)amino)-N-methyl-benzenesulfonamide (1) is disclosed along with fundamental structure-function relationships that delineate the role of each element of 1 for TNNI3K recognition. An X-ray structure of 1 bound to TNNI3K confirmed its Type I binding mode and is used to rationalize the structure-activity relationship and employed to design potent, selective, and orally bioavailable TNNI3K inhibitors. Identification of the 7-deazapurine heterocycle as a superior template (vs purine) and its elaboration by introduction of C4-benzenesulfonamide and C7- and C8-7-deazapurine substituents produced compounds with substantial improvements in potency (>1000-fold), general kinase selectivity (10-fold improvement), and pharmacokinetic properties (>10-fold increase in poDNAUC). Optimal members of the series have properties suitable for use in in vitro and in vivo experiments aimed at elucidating the role of TNNI3K in cardiac biology and serve as leads for developing novel heart failure medicines.