(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
(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
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(S)-形式的 α-甲基-N(α)-邻苯二甲酰亚胺戊二酰亚胺，但不是其 (R)-形式，增强佛波酯诱导的人白血病细胞 HL-60 产生的肿瘤坏死因子-α：光学分辨率的影响沙利度胺效应
DOI：
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发表时间：
1994
期刊：
影响因子：
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通讯作者：
S. Iwasaki
中科院分区：
文献类型：
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作者：
K. Nishimura;Y. Hashimoto;S. Iwasaki
在pH 7.4/37℃条件下，N(α)-邻苯二甲酰亚胺戊二酰亚胺(反应停)的消旋速率为566min。反应停的快速消旋作用使(S)型和(R)型化合物在促进佛波酯诱导人白血病HL-60细胞产生肿瘤坏死因子-α的活性上没有明显差异。合成了结构相关的沙利度胺类似物(S)和(R)-alpha-methyl-N(alpha)-phthalimidoglutarimides(甲基沙利度胺)的光学纯形式，它们在生理条件下不消旋。只有(S)型沙利度胺，而不是(R)型沙利度胺具有促进肿瘤坏死因子-α产生的作用，提示沙利度胺的(S)异构体可能是调节沙利度胺生物反应的活性形式。
The rate of racemization of N(alpha)-phthalimidoglutarimide (thalidomide) was determined as its half life to be 566 min at pH 7.4/37 degrees C. 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)-alpha production by human leukemia HL-60 cells. Optically pure forms of structurally related analog of thalidomide, (S)- and (R)-alpha-methyl-N(alpha)-phthalimidoglutarimides (methylthalidomides), which do not racemize under the physiological condition, were prepared. Only (S)-form of methylthalidomide, but not its (R)-form, elicited TNF-alpha production-enhancing effect, suggesting that the (S)-isomer of thalidomide would be the active form in terms of thalidomidal biological response modifying effects.