17159-79-4Relevant articles and documents
Design and synthesis of orally active dispiro 1,2,4,5-tetraoxanes; Synthetic antimalarials with superior activity to artemisinin
Amewu, Richard,Stachulski, Andrew V.,Ward, Stephen A.,Berry, Neil G.,Bray, Patrick G.,Davies, Jill,Labat, Gael,Vivas, Livia,O'Neill, Paul M.
, p. 4431 - 4436 (2006)
The design and synthesis of dispiro- and spirotetraoxanes through acid-catalyzed cyclocondensation of bis(hydroperoxides) with ketones were investigated. Various modular synthetic methods were used to enable many different analogues to be prepared from common achiral synthetic intermediates and some of the key reactions employed include reductive amination and mixed anhydride amide coupling reactions. The synthesis of 1,2,4,5-tetraoxanes was also dependent on several factors, including the structure of the ketone or aldehyde, temperature, solvent, pH, and the equilibria between the ketone and the precursors of cyclic peroxides. The required 1,2,4,5-tetraoxane was formed by crosscondensation of the bis(hydroperoxide) and the 1,4-cyclohexanedione was obtained in low temperature. Reductive amination of the ketone with various amino compounds also produced compounds in moderate to good quantities.
Smissman,Lemke
, p. 456 (1968)
An investigation into the role of 2,6-lutidine as an additive for the RuCl3-NaIO4 mediated oxidative cleavage of olefins to ketones
Watson, David W.,Gill, Matthew,Kemmitt, Paul,Lamont, Scott G.,Popescu, Mihai V.,Simpson, Iain
supporting information, p. 4479 - 4482 (2018/11/23)
2,6-Lutidine has been identified as a beneficial additive for the oxidative cleavage of olefins to ketones by NaIO4 in the presence of catalytic RuCl3, improving the yield and shortening the reaction times. In the absence of 2,6-lutidine reactions stalled at the diol intermediate with incomplete conversion to the desired ketones. The reaction protocol described herein also avoids the use of harmful solvents such as CCl4 and DCE and is tolerant of a range of functional groups.
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.
