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It has been shown to reduce alcohol consumption in all animal models tested to date. A link between daidzin's capacity to reduce alcohol consumption and its ability to increase liver mitochondrial monoamine oxidase (MAO): aldehyde dehydrogenase (ALDH\u20102) activity ratio has been established. Daidzin analogs that potently inhibit ALDH\u20102 but not MAO are the most anti\u2010dipsotropic, whereas those that also inhibit MAO are not. On the basis of these findings, it was proposed that the liver mitochondrial MAO\u2013ALDH\u20102 pathway is the primary site of action of daidzin and that a biogenic aldehyde derived from the action of MAO mediates its anti\u2010dipsotropic action. Therefore, to design and synthesize more potent anti\u2010dipsotropic analogs, structural features that would enhance ALDH\u20102 inhibition and\/or decrease MAO inhibition needed to be evaluated. Structure\u2010activity\u2010relationship (SAR) studies have revealed that a sufficient set of criteria for a potent anti\u2010dipsotropic analog is an isoflavone with a free 4\u2032\u2010OH function and a straight\u2010chain alkyl at the 7 position that has a terminal polar function such as \u2010OH, \u2010COOH, or \u2010NH<jats:sub>2<\/jats:sub>. The preferable chain lengths for the 7\u2010<jats:italic>O<\/jats:italic>\u2010\u03c9\u2010carboxy, 7\u2010<jats:italic>O<\/jats:italic>\u2010\u03c9\u2010hydroxy, and 7\u2010<jats:italic>O<\/jats:italic>\u2010\u03c9\u2010amino substituents are 5\u2264n \u226410, 2 \u2264n \u22646, and n \u22654, respectively. Analogs that meet these criteria have increased potency for ALDH\u20102 inhibition and\/or decreased potency for MAO inhibition and are, therefore, likely to be potent anti\u2010dipsotropic agents. \u00a9 2003 Wiley Periodicals, Inc. 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