坎利酮的部分合成衍生化及其对人心脏肌肉中Na+/K(+)-ATP酶活性抑制作用影响的表征。

Partial synthetic derivatization of canrenone and characterization of its impact on the inhibitory effect on Na+/K(+)-ATPase activity in human heart muscle.

作者信息

Weiland J, Megges R, Undeutsch B, Schön R, Büchting H, Repke R H

机构信息

Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.

出版信息

Steroids. 1998 Sep;63(9):464-9. doi: 10.1016/s0039-128x(98)00049-x.

DOI:10.1016/s0039-128x(98)00049-x

PMID:9727093

Abstract

To improve the weak inhibitory effect of 3-oxo-17 alpha-pregna-4,6-diene-21,17-carbolactone (canrenone, II) on Na+/K(+)-ATPase activity in human heart muscle, we have investigated the impact of hydrogenation, reduction, glycosidation, and the introduction of a 3-sulfonamido residue on the inhibitory potency of canrenone. The greatest increase in potency (> 20 times) was found for 3 beta-(alpha-L-rhamnopyranosyloxy)-5 beta, 17 alpha-pregnane-21, 17-carbolactone (IX). The 3-O-glycosides IX-XI are the first representatives of C/D-trans steroids with effector-receptor complex decay half-times longer than those of therapeutically used cardenolides.

摘要

为提高3-氧代-17α-孕甾-4,6-二烯-21,17-内酯（坎利酮，II）对人心肌中Na+/K(+)-ATP酶活性较弱的抑制作用，我们研究了氢化、还原、糖苷化以及引入3-磺酰胺基残基对坎利酮抑制效力的影响。发现3β-(α-L-鼠李吡喃糖氧基)-5β,17α-孕甾烷-21,17-内酯（IX）的效力增加最大（>20倍）。3-O-糖苷IX-XI是C/D-反式甾体的首批代表，其效应物-受体复合物衰变半衰期比治疗用强心苷类药物的更长。