53976-65-1Relevant academic research and scientific papers
Nature of the Nucleophilic Oxygenation Reagent Is Key to Acid-Free Gold-Catalyzed Conversion of Terminal and Internal Alkynes to 1,2-Dicarbonyls
Dubovtsev, Alexey Yu.,Shcherbakov, Nikolay V.,Dar'in, Dmitry V.,Kukushkin, Vadim Yu.
, p. 745 - 757 (2020/02/04)
2,3-Dichloropyridine N-oxide, a novel oxygen transfer reagent, allows the conductance of the gold(I)-catalyzed oxidation of alkynes to 1,2-dicarbonyls in the absence of any acid additives and under mild conditions to furnish the target species, including those derivatized by highly acid-sensitive groups. The developed strategy is effective for a wide range of alkyne substrates such as terminal- and internal alkynes, ynamides, alkynyl ethers/thioethers, and even unsubstituted acetylene (40 examples; yields up to 99%). The oxidation was successfully integrated into the trapping of reactive dicarbonyls by one-pot heterocyclization and into the synthesis of six-membered azaheterocycles. This synthetic acid-free route was also successfully applied for the total synthesis of a natural 1,2-diketone.
Small Molecule Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors: Hit to Lead Optimization of Systemic Agents
Londregan, Allyn T.,Wei, Liuqing,Xiao, Jun,Lintner, Nathanael G.,Petersen, Donna,Dullea, Robert G.,McClure, Kim F.,Bolt, Michael W.,Warmus, Joseph S.,Coffey, Steven B.,Limberakis, Chris,Genovino, Julien,Thuma, Benjamin A.,Hesp, Kevin D.,Aspnes, Gary E.,Reidich, Benjamin,Salatto, Christopher T.,Chabot, Jeffrey R.,Cate, Jamie H.D.,Liras, Spiros,Piotrowski, David W.
, p. 5704 - 5718 (2018/06/18)
The optimization of a new class of small molecule PCSK9 mRNA translation inhibitors is described. The potency, physicochemical properties, and off-target pharmacology associated with the hit compound (1) were improved by changes to two regions of the molecule. The last step in the synthesis of the congested amide center was enabled by three different routes. Subtle structural changes yielded significant changes in pharmacology and off-target margins. These efforts led to the identification of 7l and 7n with overall profiles suitable for in vivo evaluation. In a 14-day toxicology study, 7l demonstrated an improved safety profile vs lead 7f. We hypothesize that the improved safety profile is related to diminished binding of 7l to nontranslating ribosomes and an apparent improvement in transcript selectivity due to the lower strength of 7l stalling of off-target proteins.
Discovery of pyridone-containing imidazolines as potent and selective inhibitors of neuropeptide Y Y5 receptor
Ando, Makoto,Sato, Nagaaki,Nagase, Tsuyoshi,Nagai, Keita,Ishikawa, Shiho,Takahashi, Hirobumi,Ohtake, Norikazu,Ito, Junko,Hirayama, Mioko,Mitobe, Yuko,Iwaasa, Hisashi,Gomori, Akira,Matsushita, Hiroko,Tadano, Kiyoshi,Fujino, Naoko,Tanaka, Sachiko,Ohe, Tomoyuki,Ishihara, Akane,Kanatani, Akio,Fukami, Takehiro
experimental part, p. 6106 - 6122 (2009/12/24)
A series of 2-pyridone-containing imidazoline derivatives was synthesized and evaluated as neuropeptide Y Y5 receptor antagonists. Optimization of the 2-pyridone structure on the 2-position of the imidazoline ring led to identification of 1-(difluoromethy
Chemistry of the Phenoxathiins and Isosterically Related Heterocycles. IX. (1) The Effects of N-Oxidation on the 13C-Nmr Chemical Shifts and Coupling Constants of the 1-Azaphenoxathiin System
Martin, Gary E.
, p. 429 - 432 (2007/10/02)
The synthesis of 1-azaphenoxathiin N-oxide is described.Total assignment of the 13C-nmr spectrum and the effects of the N-oxide moiety on the chemical shifts and 1H-13C spin coupling constants are described and compared to the parent 1-azaphenoxathiin system.The potential for the use of N-oxidation induced changes in 13C-nmr chemical shifts and 1H-13C coupling constants as an assignment criterion is also discussed.
