Conformationally restricted analogs of remoxipride as potential antipsychotic agents
| Autor: | Mark H. Norman, Elizabeth B. Hollingsworth, James L. Kelley |
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| Rok vydání: | 1993 |
| Předmět: |
Male
Stereochemistry Drug Evaluation Preclinical Molecular Conformation Rats Sprague-Dawley Structure-Activity Relationship chemistry.chemical_compound Dopamine Drug Discovery medicine Remoxipride Animals Structure–activity relationship Receptor Phthalimides Raclopride Bicyclic molecule Receptors Dopamine D2 Rats chemistry Benzamides Lactam Molecular Medicine Antipsychotic Agents medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 36:3417-3423 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm00074a023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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