113249-09-5Relevant academic research and scientific papers
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.
APPLICATIONS OF α-ALKOXYORGANOCUPRATE REAGENTS IN THE REGIOSPECIFIC SYNTHESIS OF CYCLIC HOMOALDOL PRODUCTS
Linderman, Russell J.,Godfrey, Alex,Horne, Kelly
, p. 495 - 506 (2007/10/02)
Cyclic homoaldol products have been prepared via conjugate addition of α-alkoxyorganocuprate reagents to enones.The reactions are regiospecific, providing the homoaldol products in good to excellent yields.The preparation of the cuprates from the α-alkoxyorganostannane precursor is described in detail.Best results were obtained with the higher order cyano cuprate reagent using in-situ trimethylsilyl chloride.
A REACTIVITY UMPOLUNG ROUTE TO CYCLIC HOMOENOLATE ALDOL PRODUCTS VIA α-ALKOXYORGANOCUPRATE CONJUGATE ADDITIONS.
Linderman, Russell J.,Godfrey, Alex,Horne, Kelly
, p. 3911 - 3914 (2007/10/02)
Substituted α-alkoxyorganocuprate reagents readily undergo conjugate addition reactions with cyclic enones to provide homoaldol products.
