Dubur G J, Veveris M M, Weinheimer G, Bisenieks E A, Makarova N R, Kimenis A A, Uldrikis J R, Lukevics E J, Dooley D, Osswald H
Institute for Organic Synthesis, Riga (USSR), Fed. Rep. of Germany.
Arzneimittelforschung. 1989 Oct;39(10):1185-9.
This study presents the synthesis of new 1,4-dihydropyridine (DHP) derivatives which are phenoxy- and alkoxyalkyl esters of 2,6-dimethyl-4-(2-difluoromethoxyphenyl)-1,4-dihydropyridine-3,5-dica rbo xylic acid and reports on the biological activity of the compounds. It was found that the DHP derivatives showed high affinity to the DHP receptor of rat brain membranes and antagonize potently the potassium depolarization-induced vasospasm in a fashion compatible with the assumption of a calcium entry blockade. The higher vasodilating potency of especially compound III for the cerebral vasculature might represent an improved selectivity profile due to specific substitution patterns of the DHP molecule by increasing lipophilicity. Thus, the new DHP derivatives might be useful as therapeutic agents for hypertension and impaired cerebral microcirculation.
本研究介绍了新型1,4 - 二氢吡啶（DHP）衍生物的合成，这些衍生物是2,6 - 二甲基 - 4 - (2 - 二氟甲氧基苯基)-1,4 - 二氢吡啶 - 3,5 - 二羧酸的苯氧基和烷氧基烷基酯，并报道了这些化合物的生物活性。研究发现，DHP衍生物对大鼠脑膜的DHP受体表现出高亲和力，并以与钙内流阻断假设相符的方式有效拮抗钾去极化诱导的血管痉挛。特别是化合物III对脑血管具有更高的血管舒张效力，这可能是由于DHP分子通过增加亲脂性的特定取代模式而表现出改善的选择性。因此，新型DHP衍生物可能作为治疗高血压和脑微循环障碍的药物。
