Brixner D I, Ueda T, Cheng Y C, Hynes J B, Broom A D
J Med Chem. 1987 Apr;30(4):675-8. doi: 10.1021/jm00387a016.
Recent demonstrations that deazafolate analogues may act as potent inhibitors of thymidylate synthase (TS) provided a firm rationale for the synthesis of N10-propargyl derivatives of 8-deazafolate and 8-deazaaminopterin (4). A complete assignment of the 1H NMR spectra of these compounds was made possible through application of 2D (COSY) techniques at 200 MHz. Data describing the inhibition of TS derived from human leukemia (K562) cells are presented. IC50 values of 2.25 and 1.26 microM were determined for 8-deaza-10-propargylfolate (3) and 8-deaza-10-propargylaminopterin, respectively. Comparison of the data for various folate analogues reveals a striking dependence of TS inhibitory potency upon the number of nitrogens in the folate pyrazine ring.
最近的研究表明，脱氮叶酸类似物可能是胸苷酸合成酶（TS）的有效抑制剂，这为合成8-脱氮叶酸和8-脱氮氨基蝶呤的N10-炔丙基衍生物提供了坚实的理论依据（4）。通过在200 MHz下应用二维（COSY）技术，得以对这些化合物的1H NMR光谱进行完整归属。本文给出了描述源自人白血病（K562）细胞的TS抑制作用的数据。8-脱氮-10-炔丙基叶酸（3）和8-脱氮-10-炔丙基氨基蝶呤的IC50值分别测定为2.25和1.26 microM。对各种叶酸类似物数据的比较揭示了TS抑制效力对叶酸吡嗪环中氮原子数的显著依赖性。
