Preparation of dopaminergic N-alkyl-benzyltetrahydroisoquinolines using a 'one-pot' procedure in acid medium.
The preparation of N-methyl-BTHIQ (4) from N-phenylethyl-phenacetamide (1) by cyclization, reduction and N-alkylation in acid medium has been achieved in good yield in a 'one-pot' procedure. Acylation of imine (2) intermediate afforded the Z and E stereoselectivity in the enamide formation. 6-Hydroxy-BTHIQ (7) shows selectivity for D2 dopamine receptors, while its N-methylated homologue (8) displays higher affinities for both D1 and D2 receptor types, with an unexpected increase in D1 dopamine receptor affinity.
Andreu
I
I
Departamento de Farmacologia, Farmacognosia y Farmacodinamia, Facultad de Farmacia, Universidad de Valencia, Spain.
Cortes
D
D
Protais
P
P
Cassels
B K
BK
Chagraoui
A
A
Cabedo
N
N
D015259:Dopamine Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D013057:Spectrum Analysis
D015259:Dopamine Agents; D007546:Isoquinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2