- PYRIDINESULFONAMIDE DERIVATIVES AS TRAP1 MODULATORS AND USES THEREOF
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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).
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- A Practical and Robust Multistep Continuous Process for Manufacturing 5-Bromo-N-(tert-butyl)pyridine-3-sulfonamide
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A multistep continuous flow process involving (1) magnesium-halogen exchange, (2) sulfonylation with sulfuryl chloride, and (3) reaction with tert-butylamine was developed for the synthesis of an arylsulfonamide pharmaceutical intermediate in the synthesis of BMS-919373. The process was successfully implemented, including a robust control strategy to manage the levels of several process impurities, to produce 76 kg of 5-bromo-N-(tert-butyl)pyridine-3-sulfonamide (2). As the instability of the reactive intermediates and existence of strong exotherms made a batch process unsuitable for production beyond a 1 kg scale, the alternative continuous process led to a practical and robust manufacturing route to the active pharmaceutical ingredient.
- Yu, Miao,Strotman, Neil A.,Savage, Scott A.,Leung, Simon,Ramirez, Antonio
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p. 2088 - 2095
(2019/10/08)
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- Hetaryl Bromides Bearing the SO2F Group – Versatile Substrates for Palladium-Catalyzed C–C Coupling Reactions
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Synthesis of novel five- and six-membered heteroaromatic sulfonyl fluorides bearing bromine atom at various positions of the heterocyclic ring is described. The synthetic utility of these compounds is demonstrated by the Suzuki, Stille, and Negishi cross-
- Cherepakha, Artem Yu.,Stepannikova, Kateryna O.,Vashchenko, Bohdan V.,Gorichko, Marian V.,Tolmachev, Andrey A.,Grygorenko, Oleksandr O.
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p. 6682 - 6692
(2018/11/30)
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- SUBSTITUTED QUINOLINES AND METHODS FOR TREATING CANCER
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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.
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Paragraph 0322-0323
(2018/05/24)
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- Identification of Purines and 7-Deazapurines as Potent and Selective Type i Inhibitors of Troponin I-Interacting Kinase (TNNI3K)
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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.
- 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.
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p. 7431 - 7448
(2015/10/05)
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- Efficient and scalable synthesis of pyridine sulfonamides
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Short-step and scalable transformations from 2,6-dibromopyridine to 6-bromopyridine-2-sulfonamide by means of halogen-metal exchange and subsequent reaction with sulfuryl chloride followed by amidation are established. Application of the method for the synthesis of various pyridine sulfonamides is also described. Georg Thieme Verlag Stuttgart - New York.
- Emura, Takashi,Yoshino, Hitoshi,Tachibana, Kazutaka,Shiraishi, Takuya,Honma, Akie,Mizutani, Akemi,Muraoka, Terushige
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experimental part
p. 1117 - 1120
(2011/06/20)
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- COMPOUNDS AND METHODS
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Disclosed are compounds having the formula (I): wherein R1, R2, R3, R4, R5, and R6 are as defined herein, and methods of making and using the same.
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Page/Page column 69
(2011/08/04)
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- QUINAZOLINES AS POTASSIUM ION CHANNEL INHIBITORS
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A compound of formula (I) wherein A, X, Y, Z, R1 and R24 are described herein. The compounds are useful as inhibitors of potassium channel function and in the treatment and prevention of arrhythmia, IKur-associated disorders, and other disorders mediated by ion channel function.
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Page/Page column 216-217
(2011/04/14)
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- Design and synthesis of an androgen receptor pure antagonist (CH5137291) for the treatment of castration-resistant prostate cancer
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A series of 5,5-dimethylthiohydantoin derivatives were synthesized and evaluated for androgen receptor pure antagonistic activities for the treatment of castration-resistant prostate cancer. Since CH4933468, which we reported previously, had a problem wit
- Yoshino, Hitoshi,Sato, Haruhiko,Shiraishi, Takuya,Tachibana, Kazutaka,Emura, Takashi,Honma, Akie,Ishikura, Nobuyuki,Tsunenari, Toshiaki,Watanabe, Miho,Nishimoto, Ayako,Nakamura, Ryo,Nakagawa, Toshito,Ohta, Masateru,Takata, Noriyuki,Furumoto, Kentaro,Kimura, Kazuya,Kawata, Hiromitsu
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experimental part
p. 8150 - 8157
(2011/02/22)
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- Acetylenyl-pyrazolo-pyrimidine derivatives
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The present invention relates to compounds of formula (I): wherein R1 to R3, A, M, L, E, G, and J are as defined in the description and claims. The invention also relates to a process for the manufacture of such compounds, pharmaceutical compositions containing them, and methods for treating CNS disorders.
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Page/Page column 26
(2008/06/13)
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- Studies on Anticoccidial Agents. 13. Synthesis and Anticoccidial Activity of Nitropyridine-2- and -3-sulfonamides and Derivatives
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Eight nitropyridinesulfonamides andd pyridinesulfonamide N-oxides as their bioisosteres were prepared and evaluated for anticoccidial activity.Of these compounds, 2-, 4- and 5-nitropyridine-3-sulfonamides and pyridine-2- and -3-sulfonamide N-oxides were found to be active against Eimeria tenella.Thus, the relative positions, ortho or meta, of the substituents in nitropyridine-3-sulfonamides and pyridinesulfonamide N-oxides are important for anticoccidial activity.N-Substituted analogues of 5-nitropyridine-3-sulfonamide were also prepared and optimal anticoccidial activity was attained with the sulfonamide and its lower N-alkyl derivatives.The mode of action of 5-nitropyridine-3-sulfonamide was examined and found to be active in the sporozoite and the first schizogony stages.
- Morisawa, Yasuhiro,Kataoka, Mitsuru,Nagahori, Hitoshi,Sakamoto, Toshiaki,Kitano, Noritoshi,et al.
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p. 1376 - 1380
(2007/10/02)
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