Asymmetric α-substituted phenethylamines. III. The synthesis and analgesic activity of optically pure (S)- and (R)-1-aryl-2-phenylethylamines

Article abstract of DOI:10.1248/cpb.31.1659

(1S, 1'S)- and (1R, 1'R)-1-aryl-N-2'-hydroxy-1'-isopropylethyl-2-(4-substituted phenyl)ethylamines (7-13 and 18-23) were synthesized by the asymmetric reaction of (E)-(S)- and (E)-(R)-N-(2-hydroxy-1-isopropylethyl)arylmethylideneamines with Grignard reagents. The products showed 100% optical purities; their absolute configurations were determined by means of circular dichroism. These optically pure chiral amines were converted into hydrochlorides and then evaluated for analgesic activity in the acetic acid-induced mouse-writhing assay. Among these compounds, the hydrochlorides of 9 (1S:1'S, Ar = 2-thienyl,R = H), 13 (1S: 1'S, Ar = 2-thienyl, R = MeO), 19 (1R:1'R, Ar = 4-methoxyphenyl, R = H), 20 (1R: 1'R, Ar = 2-thienyl, R = H), and 23 (1S: 1'S, Ar = 2-thienyl, R = OH) showed inhibition of the writhing; they were about equipotent with (-)-pentazocine hydrochloride. Moreover, the hydrochlorides of 8 (1S: 1'S, Ar = 4-methoxyphenyl, R = H), 13 (1S: 1'S, Ar = 2-thienyl, R = MeO), 18 (1R: 1'R, Ar = phenyl, R = H), 19 (1R:1'R, Ar = 4-methoxyphenyl, R = H), 20 (1R: 1'R, Ar = 2-thienyl, R = H), and 21 (1R: 1'R, Ar = 2-thienyl, R = MeO) were not antagonized by (-)-naloxone hydrochloride.

Full text of DOI:10.1248/cpb.31.1659

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