Synthesis and in Vitro Evaluation of 2,3-Dimethoxy-5-(fluoroalkyl)-Substituted Benzamides

High-Affinity Ligands for CNS Dopamine D2 Receptors

John E. Bishop, Chester A. Mathis, John M. Gerdes, John M. Whitney, Allison M. Eaton, Richard Mailman

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

A number of 2,3-dimethoxy-5-(fluoroalkyl)-N-[(l-ethyl-2-pyrrolidinyl)methyl]benzamides (with or without a 6-hydroxy group) were synthesized and evaluated as dopamine D2 receptor ligands. The parent acids were synthesized via the Claisen rearrangement of the appropriate O-allyl ethers, which were derived from o-vanillic acid or 2,3-di- methoxysalicylic acid. A decrease in reactivity was found to be characteristic of pentasubstituted benzoates, and difficulties were encountered with the introduction of fluorine onto the ethyl side chains. The (fluoroethyl)- and (fluoropropyl)salicylamides were 5 times more potent than the corresponding benzamides in inhibiting [3H]spiperone binding to the D2 receptor. These (fluoroalkyl)salicylamides are of potential value for in vivo positron emission tomography (PET) studies upon the basis of their relatively selective, high potency binding affinity for the D2 receptor.

Original languageEnglish (US)
Pages (from-to)1612-1624
Number of pages13
JournalJournal of Medicinal Chemistry
Volume34
Issue number5
DOIs
StatePublished - May 1 1991

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Salicylamides
Benzamides
Dopamine D2 Receptors
Vanillic Acid
Ligands
Spiperone
Ethers
Fluorine
Benzoates
Positron-Emission Tomography
Acids
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Bishop, John E. ; Mathis, Chester A. ; Gerdes, John M. ; Whitney, John M. ; Eaton, Allison M. ; Mailman, Richard. / Synthesis and in Vitro Evaluation of 2,3-Dimethoxy-5-(fluoroalkyl)-Substituted Benzamides : High-Affinity Ligands for CNS Dopamine D2 Receptors. In: Journal of Medicinal Chemistry. 1991 ; Vol. 34, No. 5. pp. 1612-1624.
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Synthesis and in Vitro Evaluation of 2,3-Dimethoxy-5-(fluoroalkyl)-Substituted Benzamides : High-Affinity Ligands for CNS Dopamine D2 Receptors. / Bishop, John E.; Mathis, Chester A.; Gerdes, John M.; Whitney, John M.; Eaton, Allison M.; Mailman, Richard.

In: Journal of Medicinal Chemistry, Vol. 34, No. 5, 01.05.1991, p. 1612-1624.

Research output: Contribution to journalArticle

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