Joslyn A F, Luchowski E, Triggle D J
Department of Biochemical Pharmacology, School of Pharmacy, State University of New York, Buffalo 14260.
J Med Chem. 1988 Aug;31(8):1489-92. doi: 10.1021/jm00403a002.
A series of 1,n-alkanediylbis(1,4-dihydropyridines) (n = 2, 4, 6, 8, 10, 12) bridged at C3 of 2,6-dimethyl-3-carboxy-5-carbethoxy-4-(3-nitrophenyl)-1,4-dihydropyridin e were synthesized and evaluated in a radioligand binding assay, [3H]nitrendipine in intestinal smooth muscle, as Ca2+ channel ligands. Binding activity was comparable to that of nitrendipine itself but independent of chain length, suggesting the lack of a major binding contribution by the second 1,4-dihydropyridine group. Analogues lacking the second 1,4-dihydropyridine nucleus or possessing an inactive function (4-nitrophenyl) were no less active, confirming that this series of ligands likely does not bridge adjacent 1,4-dihydropyridine receptors of the Ca2+ channel.
合成了一系列在2,6-二甲基-3-羧基-5-乙氧羰基-4-(3-硝基苯基)-1,4-二氢吡啶的C3位桥连的1,n-亚烷基双(1,4-二氢吡啶)(n = 2, 4, 6, 8, 10, 12)，并在放射性配体结合试验中作为Ca2+通道配体，用[3H]尼群地平在肠道平滑肌中进行了评估。结合活性与尼群地平本身相当，但与链长无关，这表明第二个1,4-二氢吡啶基团对结合没有主要贡献。缺少第二个1,4-二氢吡啶核或具有无活性官能团(4-硝基苯基)的类似物活性并不低，这证实了这一系列配体可能不会桥连Ca2+通道相邻的1,4-二氢吡啶受体。
