Harada N, Hongu M, Tanaka T, Kashida T, Narasaki N, Ohohashi M, Oda K, Hashiyama T, Tsujihara K
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Chem Pharm Bull (Tokyo). 1995 Oct;43(10):1793-6. doi: 10.1248/cpb.43.1793.
In an attempt to improve the effectiveness and bioavailability of 6-mercaptopurine, various kinds of water-soluble analogues, such as 6-S-aminoacyloxymethyl mercaptopurine derivatives (3a--m) and 6-S,9-disubstituted derivates (7a,b and 9a,b), were synthesized. These compounds were evaluated for activity to augment antitumor immunity by using a double grated tumor system. Antitumor activities against solid tumors (sarcoma 180 and colon 26) were also evaluated. Many compounds exhibited potent activities in both test systems. In particular, the aminopropionate derivative (3a) and the L-glutamate derivative (3f) showed significant enhancement of antitumor immunity together with potent antitumor activities.
为提高6-巯基嘌呤的有效性和生物利用度，合成了各种水溶性类似物，如6-S-氨基酰氧基甲基巯基嘌呤衍生物（3a - m）和6-S,9-二取代衍生物（7a,b和9a,b）。通过使用双格栅肿瘤系统评估这些化合物增强抗肿瘤免疫力的活性。还评估了对实体瘤（肉瘤180和结肠癌26）的抗肿瘤活性。许多化合物在两个测试系统中均表现出强效活性。特别是，氨基丙酸酯衍生物（3a）和L-谷氨酸衍生物（3f）显示出抗肿瘤免疫力的显著增强以及强效的抗肿瘤活性。
