Two 2-aryl imidazo [2,1-a] isoquinolines were synthesized and tested for pregnancy terminating activities. Both of them are new compounds and their structures were confirmed by IR, (HNMR)-H-1, MS and elemental analysi...Two 2-aryl imidazo [2,1-a] isoquinolines were synthesized and tested for pregnancy terminating activities. Both of them are new compounds and their structures were confirmed by IR, (HNMR)-H-1, MS and elemental analysis. They both showed high activities in NIH mice.展开更多
Contragestazolin (L14105) belongs to the class of 2 phenyl triazole isoquinolines. When given subcutaneously, intramuscularly or orally showed potential pregnancy terminating activity in mice, rats, hamsters...Contragestazolin (L14105) belongs to the class of 2 phenyl triazole isoquinolines. When given subcutaneously, intramuscularly or orally showed potential pregnancy terminating activity in mice, rats, hamsters and guinea pigs, but the dialy doses of oral administration needed were 7.1, 6.3 and 47.6 times (for mouse, rat and hamster) greater than those needed parenterally. L14105 had low affinity to rat uterine progesterone receptor. When cultured human decidual cells were exposed to L14105 0.077～0.155 mmol/L for 24～48 h, the cells' viability markedly dropped and structural changes occurred in comparison with controls. Histological examination of conceptuses of rats showed edema, degeneration, necrosis and atrophy or disappearance of decidual cells nuclei and absorption of embryos after the sc administration of L14105 5 mg/kg for 24～48 h. L14105 stimulated the contractile force of uterine smooth muscle in vivo or in vitro. Conclusion: L14105 shows a very high pregnancy terminating activity. Multiple oral administration is also effective. The mode of action of contragestation is related to damage of decidual cells and stimulation of uterine contractility.展开更多
In order to clarify the structural requirement of pregnancy-terminating drugs, the quantitative structure-activity relationship (QSAR) of 2-aryl imidazo[2,1-a]isoquinolines was studied on the basis of quantum mechanic...In order to clarify the structural requirement of pregnancy-terminating drugs, the quantitative structure-activity relationship (QSAR) of 2-aryl imidazo[2,1-a]isoquinolines was studied on the basis of quantum mechanical calculation and multiple regression analysis. A Good correlation equation was obtained (r2=0.925, q2=0.871). Some new compounds were designed according to the equation. Two of them, compounds 21 and 22, were synthesized and evaluated in NIH mice. The results showed that the difference of activity between 21 (median effective dose ED50=0.943 mg/kg/day) and 22 (ED50=1.099 mg/kg/day) was small and both of them were potent. It is also agreed with the computational results. Compared with L14105 which is the most potent pregnancy-terminating agent, these two compounds possess high activity. The evaluation of the anti-implanting activity showed that they were 100% effective at tested dosage 50.0, 25.0, 12.5 mg/kg/day×3 days in oral administration, which proved the both of them had anti-implanting activity and low first-pass effects.展开更多
文摘Two 2-aryl imidazo [2,1-a] isoquinolines were synthesized and tested for pregnancy terminating activities. Both of them are new compounds and their structures were confirmed by IR, (HNMR)-H-1, MS and elemental analysis. They both showed high activities in NIH mice.
文摘Contragestazolin (L14105) belongs to the class of 2 phenyl triazole isoquinolines. When given subcutaneously, intramuscularly or orally showed potential pregnancy terminating activity in mice, rats, hamsters and guinea pigs, but the dialy doses of oral administration needed were 7.1, 6.3 and 47.6 times (for mouse, rat and hamster) greater than those needed parenterally. L14105 had low affinity to rat uterine progesterone receptor. When cultured human decidual cells were exposed to L14105 0.077～0.155 mmol/L for 24～48 h, the cells' viability markedly dropped and structural changes occurred in comparison with controls. Histological examination of conceptuses of rats showed edema, degeneration, necrosis and atrophy or disappearance of decidual cells nuclei and absorption of embryos after the sc administration of L14105 5 mg/kg for 24～48 h. L14105 stimulated the contractile force of uterine smooth muscle in vivo or in vitro. Conclusion: L14105 shows a very high pregnancy terminating activity. Multiple oral administration is also effective. The mode of action of contragestation is related to damage of decidual cells and stimulation of uterine contractility.
文摘In order to clarify the structural requirement of pregnancy-terminating drugs, the quantitative structure-activity relationship (QSAR) of 2-aryl imidazo[2,1-a]isoquinolines was studied on the basis of quantum mechanical calculation and multiple regression analysis. A Good correlation equation was obtained (r2=0.925, q2=0.871). Some new compounds were designed according to the equation. Two of them, compounds 21 and 22, were synthesized and evaluated in NIH mice. The results showed that the difference of activity between 21 (median effective dose ED50=0.943 mg/kg/day) and 22 (ED50=1.099 mg/kg/day) was small and both of them were potent. It is also agreed with the computational results. Compared with L14105 which is the most potent pregnancy-terminating agent, these two compounds possess high activity. The evaluation of the anti-implanting activity showed that they were 100% effective at tested dosage 50.0, 25.0, 12.5 mg/kg/day×3 days in oral administration, which proved the both of them had anti-implanting activity and low first-pass effects.
