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J Med Chem. 2012 Apr 12;55(7):3242-9. doi: 10.1021/jm201692d. Epub 2012 Mar 23.

Synthesis and evaluation of a set of para-substituted 4-phenylpiperidines and 4-phenylpiperazines as monoamine oxidase (MAO) inhibitors.

Author information

1
NeuroSearch Sweden AB, Arvid Wallgrens Backe 20, S-413 46 Göteborg, Sweden. fpe@neurosearch.se

Abstract

A series of para-substituted 4-phenylpiperidines/piperazines have been synthesized and their affinity to recombinant rat cerebral cortex monoamine oxidases A (MAO A) and B (MAO B) determined. Para-substituents with low dipole moment increased the affinity to MAO A, whereas groups with high dipole moment yielded compounds with no or weak affinity. In contrast, the properties affecting MAO B affinity were the polarity and bulk of the para-substituent, with large hydrophobic substituents producing compounds with high MAO B affinity. In addition, these compounds were tested in freely moving rats and the effect on the post-mortem neurochemistry was measured. A linear correlation was demonstrated between the affinity for MAO A, but not MAO B, and the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) in the striatum.

PMID:
22385498
DOI:
10.1021/jm201692d
[Indexed for MEDLINE]

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