SYNTHESIS AND INVITRO EVALUATION OF 2,3-DIMETHOXY-5-(FLUOROALKYL)-SUBSTITUTED BENZAMIDES - HIGH-AFFINITY LIGANDS FOR CNS DOPAMINE-D2 RECEPTORS

被引:48
作者
BISHOP, JE
MATHIS, CA
GERDES, JM
WHITNEY, JM
EATON, AM
MAILMAN, RB
机构
[1] UNIV CALIF BERKELEY LAWRENCE BERKELEY LAB,DIV RES MED & RADIAT BIOPHYS,MS 55-121,1 CYCLOTRON RD,BERKELEY,CA 94720
[2] UNIV N CAROLINA,SCH MED,BRAIN & DEV RES CTR,DEPT PSYCHIAT,CHAPEL HILL,NC 27599
[3] UNIV N CAROLINA,SCH MED,DEPT PHARMACOL,CHAPEL HILL,NC 27599
关键词
D O I
10.1021/jm00109a013
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A number of 2,3-dimethoxy-5-(fluoroalkyl)-N-[(1-ethyl-2-pyrrolidinyl]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 omicron-vanillic acid or 2,3-dimethoxysalicylic 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 [H-3]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.
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页码:1612 / 1624
页数:13
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