Weier R M, Hofmann L M
J Med Chem. 1977 Oct;20(10):1304-8. doi: 10.1021/jm00220a015.
Several analogues of the previously reported steroidal spirolactone 1a were synthesized. These analogues bear C-6 substituents and include the 6beta-deuterio (1c), the 6beta-bromo (1d), the 6beta-methyl (1e), and the 6alpha-methyl (7) compounds. The 6beta-hydroxy compound 1b, a human and animal metabolite of 1a, was also synthesized. On subcutaneous administration to adrenalectomized rats, all these compounds exhibited the ability to block the effects of administered deoxycorticosterone acetate (DCA) (MED less than or equal to 0.58 mg). Only 7 failed to show anti-DCA effects at the standard test level on oral administration. None was significantly superior in potency to the parent compound 1a.
合成了几种先前报道的甾体螺内酯1a的类似物。这些类似物带有C-6取代基，包括6β-氘代物（1c）、6β-溴代物（1d）、6β-甲基物（1e）和6α-甲基物（7）。6β-羟基化合物1b，是1a的人和动物代谢产物，也被合成出来。对肾上腺切除的大鼠皮下给药时，所有这些化合物都表现出能够阻断给予的醋酸脱氧皮质酮（DCA）的作用（最小有效剂量小于或等于0.58毫克）。只有7在口服给药的标准测试水平下未显示出抗DCA作用。在效力上没有一种明显优于母体化合物1a。
