25637-16-5Relevant articles and documents
Ni-Catalyzed Formal Cross-Electrophile Coupling of Alcohols with Aryl Halides
Lin, Quan,Ma, Guobin,Gong, Hegui
, p. 14102 - 14109 (2021/11/20)
Direct coupling of unactivated alcohols remains a challenge in current synthetic chemistry. We herein demonstrate a strategy building upon in situ halogenation/reductive coupling of alcohols with aryl halides to forge Csp2-Csp3 bonds. The combination of 2-chloro-3-ethylbenzo[d]oxazol-3-ium salt (CEBO) and TBAB as the mild bromination reagents enables rapid transformation of a wide range of alcohols to their bromide counterparts within one to 5 min in CH3CN and DMF, which is compatible with the Ni-catalyzed cross-electrophile coupling conditions in the presence of a chemical reductant. The present method is suitable for arylation of a myriad of structurally complex alcohols with no need for prepreparation of alkyl halides. More importantly, the mild and kinetically rapid bromination process has shown good selectivity in the bromination/arylation of symmetric diols and less sterically hindered hydroxyl groups in polyols, thus offering promise for selective functionalization of diols and polyols without laborious protecting/deprotecting operations. The practicality of this work is also evident in the arylation of a number of carbohydrates, drug compounds, and naturally occurring alcohols.
Development of Fluorinated Analogues of Perhexiline with Improved Pharmacokinetic Properties and Retained Efficacy
Tseng, Chih-Chung,Noordali, Hannah,Sani, Monica,Madhani, Melanie,Grant, Denis M.,Frenneaux, Michael P.,Zanda, Matteo,Greig, Iain R.
supporting information, p. 2780 - 2789 (2017/04/21)
We designed and synthesized perhexiline analogues that have the same therapeutic profile as the parent cardiovascular drug but lacking its metabolic liability associated with CYP2D6 metabolism. Cycloalkyl perhexiline analogues 6a-j were found to be unsuitable for further development, as they retained a pharmacokinetic profile very similar to that shown by the parent compound. Multistep synthesis of perhexiline analogues incorporating fluorine atoms onto the cyclohexyl ring(s) provided a range of different fluoroperhexiline analogues. Of these, analogues 50 (4,4-gem-difluoro) and 62 (4,4,4′,4′-tetrafluoro) were highly stable and showed greatly reduced susceptibility to CYP2D6-mediated metabolism. In vitro efficacy studies demonstrated that a number of derivatives retained acceptable potency against CPT-1. Having the best balance of properties, 50 was selected for further evaluation. Like perhexiline, it was shown to be selectively concentrated in the myocardium and, using the Langendorff model, to be effective in improving both cardiac contractility and relaxation when challenged with high fat buffer.
5-MEMBERED HETEROCYCLE-BASED P38 KINASE INHIBITORS
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Page/Page column 85; 86, (2010/02/10)
Provided are 5-membered heterocycle-based p38 kinase inhibitors. Further provided are pyrazole and imidazole-based p38 kinase, including p38α and p38β kinase, inhibitors. Pharmaceutical compositions containing the compounds are also provided. Methods of u
