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J Med Chem. 1993 Oct 29;36(22):3417-23.

Conformationally restricted analogues of remoxipride as potential antipsychotic agents.

Author information

1
Division of Organic Chemistry, Burroughs Wellcome Co., Research Triangle Park, North Carolina 27709.

Abstract

Several conformationally restricted derivatives of (S)-3-bromo-N-((1-ethyl-2-pyrrolidinyl)methyl)-2,6-dimethoxybenzamide (remoxipride) were synthesized and evaluated in vitro for their ability to inhibit [3H]raclopride binding at the dopamine D-2 receptor. The cyclic benzamides designed to mimic the intramolecular hydrogen bonding of desmethylremoxipride (4, FLA-797) included 2,3-dihydro-4H-1,3-benzoxazin-4-ones, 2,3-dihydro-4H-1,3-benzthiazin-4-ones, phthalimides, 1-isoindolinones, 1,2-benzisothiazol-3(2H)-ones, and 1,2-benzisothiazol-3(2H)-one 1,1-dioxides. In this series, enhanced affinities to the dopamine D-2 receptor were not observed. The phthalimidine analogue 24b ((S)-6-chloro-2-(1-ethylpyrrolidinyl)-1-isoindolinone) exhibited the highest affinity to the dopamine D-2 receptor with an IC50 of 1.3 microM, which was equipotent to remoxipride.

PMID:
7901417
DOI:
10.1021/jm00074a023
[Indexed for MEDLINE]

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