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)
SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF
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Page/Page column 6, (2018/03/09)
Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders. Orally delivered formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.
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.
