摘要
目的 研究系列苯并二氢吡喃化合物的构效关系 ,为设计优良的绝经后骨质疏松症防治药物提供理论依据。方法 在综合考察雷洛昔芬和异丙氧基异黄酮的基础上 ,设计合成一系列苯并二氢吡喃化合物 ,从整体水平考察化合物A对去卵巢大鼠骨质疏松的影响 ,从细胞水平研究C单独给药以及与雌二醇联合给药对人成骨细胞株HOSTE85增殖的影响 ,并均在 0 1μmol·L-1水平考察比较化合物BE对HOSTE85增殖的影响。结果 化合物A可一定程度对抗去卵巢大鼠骨质疏松症。C( 1 0nmol·L-1,0 1μmol·L-1)对HOSTE85具有显著增殖作用 ,C与雌二醇联合给药显著拮抗雌二醇对HOSTE85的增殖作用 ,故C可能为雌激素受体的部分激动剂。C、D( 0 1μmol·L-1)对HOSTE85具有显著增殖作用。结论 以A作为母体化合物 ,侧链引入碱性基团 ,对其结构修饰设计抗绝经后骨质疏松症药物是可行的。
AIM To provide theoratic data for designing optimal drugs against postmenopausal osteoporosis by studying the structure effect relationship of a series of benzodihydropyran derivatives. METHODS A series of benzodihydropyranderivatives were designed and synthesized in view of comprehensive observations of raloxifene and ipriflvone. The activity of A against osteoporosis was evaluated by observing their effects on ovariectomized rats in vivo .The effects of C and C coadministering with estrodiol on the proliferation of human osteoblast HOS TE85 were studied by cell culture. In addition, the effects of B～E(10 -7 mol·L -1 )on the proliferation of human osteoblast HOS TE85 were studied. RESULTS A had some activity against osteoporosis on ovariectomized rats. C(10 -9 mol·L -1 ,10 -7 mol·L -1 ) significantly helped proliferation of HOS TE85 and antagonized proliferation activity of estrodiol coadministering with estrodiol. Therefore C might be a part agonist of estrogen receptor. C and D (10 -7 mol·L -1 ) significantly helped proliferation of HOS TE85. CONCLUSION It is feasible that the drugs against postmenopausal osteoporosis are designed by introducing basic groups to the side chain of A and modifying the structure of A.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2001年第5期518-521,共4页
Chinese Pharmacological Bulletin
基金
广东省自然科学基金资助课题
No 0 0 0 942
