PMID: 12166939Aug 9, 2002Paper

(+)-Dinapsoline: an efficient synthesis and pharmacological profile of a novel dopamine agonist

Journal of Medicinal Chemistry
Sing-Yuen SitGraham Johnson

Abstract

A highly convergent synthesis was developed for the novel dopamine agonist dinapsoline (12) (Ghosh, D.; Snyder, S. E.; Watts, V. J.; Mailman, R. B.; Nichols, D. E. 8,9-Dihydroxy-2,3,7, 11b-tetrahydro-1H-naph[1,2,3-de]isoquinoline: A Potent Full Dopamine D(1) Agonist Containing a Rigid beta-Phenyldopamine Pharmacophore. J. Med. Chem. 1996, 39 (2), 549-555). The crucial step in the new synthesis was a free radical-initiated cyclization to give the complete dinapsoline framework. The improved synthesis required half as many steps as the original procedure (Nichols, D. E.; Mailman, R.; Ghosh, D. Preparation of novel naphtho[1,2,3-de]isoquinolines as dopamine receptor ligands. PCT Int. Appl. WO 9706799 A1, Feb 27, 1997). One of the late-stage intermediates (11) was resolved into a pair of enantiomers. From there, the (R)-(+)-12 (absolute configuration by X-ray) of dinapsoline was identified as the active enantiomer. In unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats, (+)-dinapsoline showed robust rotational behavior comparable to that of an external benchmark, trans-4,5,5a,6,7,11b-hexahydro-2-propyl-benzo[f]thieno[2,3-c]quinoline-9,10-diol, hydrochloride 18 (Michaelides, M. R.; Hong, Y. Preparation of heterotetracyclic compounds...Continue Reading

References

Dec 15, 1992·European Journal of Pharmacology·J W KebabianM Williams
Jul 4, 1989·European Journal of Pharmacology·T W LovenbergR B Mailman
Nov 1, 1974·The Journal of Organic Chemistry·I W Mathison, P H Morgan
Jun 9, 1999·Annals of Neurology·O RascolJ G Nutt

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Citations

Feb 5, 2004·Bioorganic & Medicinal Chemistry·Sing-Yuen SitRichard B Mailman
Jul 22, 2008·Medicinal Research Reviews·Jing ZhangAo Zhang
Apr 23, 2004·Journal of Neurophysiology·Pavel I OrtinskiStefano Vicini
Apr 18, 2013·Angewandte Chemie·Harald WeinstablMark Lautens
Jan 29, 2014·Chemical Communications : Chem Comm·Zhuangzhi ShiFrank Glorius
May 25, 2021·Journal of the American Chemical Society·Yidong LiuKarl Anker Jørgensen

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