(S)-FORM OF α-METHYL-N(α)-PHTHALIMIDOGLUTARIMIDE, BUT NOT ITS (R)-FORM, ENHANCED PHORBOL ESTER-INDUCED TUMOR NECROSIS FACTOR-α PRODUCTION BY HUMAN LEUKEMIA CELL HL-60 : IMPLICATION OF OPTICAL RESOLUTION OF THALIDOMIDAL EFFECTS

概要

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The rate of racemization of N(α)-phthalimidoglutarimide (thalidomide) was determined as its half life to be 566 min at pH 7.4/37℃. This fast racemization of thalidomide resulted in no apparent difference between (S)- and (R)-forms of the compound on enhancing activity of phorbol ester-induced tumor necrosis factor (TNF)-α production by human leukemia HL-60 cells. Optically pure forms of structurally related analog of thalidomide, (S)- and (R)-α -methyl-N(α)-phthalimidoglutarimides (methylthalidomides), which do not racemize under the physiological condition, were prepared. Only (S)-form of methylthalidomide, but not its (R)-form, elicited TNF-α production-enhancing effect, suggesting that the (S)-isomer of thalidomide would be the active form in terms of thalidomidal biological response modifying effects.
公益社団法人日本薬学会の論文
1994-05-15