Butyrophenone analogues: Synthesis of 2-methyl-3-ethyl-5-aminoethyl-4,5,6,7-tetrahydroindol-4-ones, and their affinities for d1, d2 and 5-ht2a receptors

Abstract Starting from 2-methyl-3-ethyl-1H-4,5,6,7-tetrahydroindol-4-one 3 we have prepared 2-methyl-3-ethyl-5-morpholinoethyl-1H-4, 5,6,7-tetrahydroindol-4-one, ( 1 ) and 2-methyl-3-ethyl-5-(4- o -methoxyphenyl-1-piperazinoethyl)-1H-4,5,6,7-tetrahydroindol-4-one ( 2 ) as butyrophenone analogues of the neuroleptic molindone. The affinities of these compounds for D 1 and D 2 dopamine and 5-HT 2A serotonin receptors were evaluated in vitro . The affinity of 1 for D 2 receptors is less than that of molindone (pKi's 6.23 and 7.48 respectively) and that of 2 similar (pK i 7.55). Both compounds bind to 5-HT 2A receptors, the affinity of 2 being significantly greater than that of molindone (pK i 's of 7.04 and 5.85, and pA2′s of 7.50 and 6.18, respectively).