Synthesis of N-diisopropyl phosphoryl benzyltetrahydroisoquinoline, a new class of mitochondrial complexes I and III inhibitors.
The synthesis of N-(O,O-diisopropylphosphoryl)-benzyltetrahydroisoquinoline (3) has been achieved in a 'one pot' procedure from imine (2) and diisopropyl-phosphorochloridate (1) generated in situ (POCl3 + iPrOH). Compound 3 is the first benzyltetrahydroisoquinoline derivative found to be a potent inhibitor of mitochondrial complexes I and III, and therefore it opens a new perspective with this series of compounds as they can be considered as new class of antitumor agents.
Andreu
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I
Departamento de Farmacología, Farmacognosia y Farmacodinamia, Universidad de Valencia, Burjassot, Spain.
Cabedo
N
N
Tormo
J R
JR
Bermejo
A
A
Mello
R
R
Cortes
D
D
D000818:Animals; D002417:Cattle; D004579:Electron Transport / Q000187:drug effects; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III