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

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 D1 and D2 dopamine and 5-HT2A serotonin receptors were evaluated in vitro. The affinity of 1 for D2 receptors is less than that of molindone (pKiʹs 6.23 and 7.48 respectively) and that of 2 similar (pKi 7.55). Both compounds bind to 5-HT2A receptors, the affinity of 2 being significantly greater than that of molindone (pKiʹs of 7.04 and 5.85, and pA2′s of 7.50 and 6.18, respectively).