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Synthesis and anti-tetrabenazine activity of c-3 analogues of dimethyl-2-phenylmorpholines

Authors :
F. E. Soroko
David Lee Musso
Barrett R. Cooper
G. Evan Boswell
James L. Kelley
Source :
Journal of Heterocyclic Chemistry. 33:33-39
Publication Year :
1996
Publisher :
Wiley, 1996.

Abstract

A series of analogues of 2-phenylmorpholines with alkyl substituents at the C-3 position were synthesized for anti-tetrabenazine (anti-TBZ) testing in mice. The target compounds were prepared by reaction of (2-bromoalkyl) phenyl ketones 21a-h with the appropriate aminoalcohol 20a-b to form morpholinols 22a-h. Hydride reduction of the morpholinols gave aminodiols 23a-h which were cyclized to morpholines 6, 8, 10–12, 14–16, 18 and 19 by acid catalaysis. Compounds 7, 9, 13 and 17 were prepared by reductive formylation. The smaller straight chain substituents of 6, 8, 12 and 15, and the beta branching of the iso-butyl group of 16 were well tolerated; anti-tetrabenazine ED50′s were comparable to compounds 2–5. The α-branched, N-methylated, and side chain aryl derivatives were less active.

Details

ISSN :
19435193 and 0022152X
Volume :
33
Database :
OpenAIRE
Journal :
Journal of Heterocyclic Chemistry
Accession number :
edsair.doi...........7022b12ac437e54955935638cb567577
Full Text :
https://doi.org/10.1002/jhet.5570330106