Synthesis of N-diisopropyl phosphoryl benzyltetrahydroisoquinoline, a new class of mitochondrial complexes I and III inhibitors

I Andreu; N Cabedo; J R Tormo; A Bermejo; R Mello; D Cortes

doi:10.1016/s0960-894x(00)00262-6

Synthesis of N-diisopropyl phosphoryl benzyltetrahydroisoquinoline, a new class of mitochondrial complexes I and III inhibitors

Bioorg Med Chem Lett. 2000 Jul 3;10(13):1491-4. doi: 10.1016/s0960-894x(00)00262-6.

Authors

I Andreu¹, N Cabedo, J R Tormo, A Bermejo, R Mello, D Cortes

Affiliation

¹ Departamento de Farmacología, Farmacognosia y Farmacodinamia, Universidad de Valencia, Burjassot, Spain.

PMID: 10888340
DOI: 10.1016/s0960-894x(00)00262-6

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cattle
Electron Transport / drug effects
Electron Transport Complex I
Electron Transport Complex III / antagonists & inhibitors*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Isoquinolines / chemical synthesis*
Isoquinolines / chemistry
Isoquinolines / pharmacology*
Magnetic Resonance Spectroscopy
Mitochondria / enzymology
Mitochondria / metabolism*
NADH, NADPH Oxidoreductases / antagonists & inhibitors*
Oxidation-Reduction

Substances

Enzyme Inhibitors
Isoquinolines
NADH, NADPH Oxidoreductases
Electron Transport Complex I
Electron Transport Complex III