✍ Scribed by Swier Copinga; Durk Dijkstra; Jan B. de Vries; Cor J. Grol; Alan S. Horn
No coin nor oath required. For personal study only.
Based on the hypothesis that simultaneous stimulation of dopamine D~1~ and ‐D~2~ receptors could be beneficial for the treatment of Parkinson's disease^7,13^, 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 D~1~/D~2~‐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 D~1~ and D~2~ receptors and has the same ability as DPAT (1), a mixed D~1~/D~2~‐receptor agonist, to induce locomotor activity in mice rendered acutely akinetic with reserpine.
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## Abstract 2‐Propyl‐8‐oxo‐1‐[(2′‐(1H‐tetrazole‐5‐yl) biphenyl‐4‐yl)methyl]‐4, 5, 6, 7‐tetrahydrocyclohept imidazole (KT3‐671), which has been found to be a potent and selective angiotesin II receptor antagonist, was synthesized in ^14^C‐labelled form by using potassium[^14^C]‐cyanide. [^14^C](KT3‐