Structure-effect relation of a series of benzodihydropyran derivatives against osteroporosis

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·L1-)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.