Synthesis and pharmacological evaluation of 5,6,7,8-tetrahydro-6-[propyl[2-(2-thienyl)ethyl]amino]-1,2-naphthalenediol: A novel non-selective dopamine-receptor agonist†
2010
Based on the hypothesis that simultaneous stimulation of dopamine-D1 and -D2 receptors could be beneficial for the treatment of Parkinson's disease7,13, we prepared 5,6,7,8-tetrahydro-6-[propyl[2-(2-thienyl)ethyl]amino]-1,2-naphthalenediol (PTAT, 4), the diol analogue of N-0437 (3), as a potential mixed D1/D2-receptor agonist. The synthesis of 4 was carried out via a new strategy. The crucial step in this strategy was the conversion of 1-
diazo-4-(2,3-dimethoxyphenyl)-
2-butanone(15) to the key intermediate 5,6-dimethoxy-
2-tetralone(9) via a
rhodium(II)-
acetate-catalysed cyclisation, followed by transformation under the influence of
trifluoroacetic acid. Pharmacological evaluation of the dopaminergic properties of PTAT (4) revealed that this compound displays high affinity for both D1 and D2 receptors and has the same ability as DPAT (1), a mixed D1/D2-receptor agonist, to induce locomotor activity in mice rendered acutely
akineticwith
reserpine.
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