摘要
4-甲基-7-羟基-6-或-8-烯丙基香豆素是一类新的辐射防护剂,但由于其脂、水溶性都很小,影响药(?)在体内的吸收及口服效果。为改善其溶解度,从增加有效基本结构的亲水或亲脂性的角度,合成了14个香豆素衍生物,测定抗辐射活性并研究了亲水,亲脂性与活性之间的关系,获得一定的结果。5a和6a能在油酸乙酯中溶解,后者在水中也有一定的溶解性,且二者都保持了活性。
4-Methyl-7-hydroxy-6 or 8-allylcoumarin, a new type of radioprotectors, has poor solubility in water and in oil, which influences markedly its absorption in body and effectiveness of peroral administration. For improving its solubility, 14 coumarin derivatives were synthesized on the basis of increasing its hydro- or lipophilicity, and studied preliminarily on their toxicities, radioprotective activities, and relations between their hydro- or lipophilicity and activities. It is found that both compounds (5a, 6a), can be dissolved in ethyl oleate and the latter in water partially as well, retain the radioprotective activities basically, and improve the survival of 65 % (P<0. 01) of mice exposed to 9.0 Gy ^(60)Coγ-ray when administered before irradiation. In synthesis, von Pechmann reaction was improved; 6-allyl intermediate was synthesized by the method of blocking the 8-position by iodine, and the process was studied. Mannich base was synthesized under high pressure by using CH_2Cl_2 as C_1 synthon.
出处
《药学学报》
CAS
CSCD
北大核心
1993年第4期266-272,共7页
Acta Pharmaceutica Sinica
关键词
辐射防护
香豆素衍生物
亲水亲脂性
Radioprotectant
Coumarin derivatives
Mannich base
Lipophilicity
