Tanouchi T, Kawamura M, Ohyama I, Kajiwara I, Iguchi Y, Okada T, Miyamoto T, Taniguchi K, Hayashi M, Iizuka K, Nakazawa M
J Med Chem. 1981 Oct;24(10):1149-55. doi: 10.1021/jm00142a006.
The enzyme thromboxane (TX) synthetase is inhibited by pyridine. The beta-substituted pyridine derivatives showed higher inhibitory potency than the gamma-substituted ones having the same side chain. Among the beta-substituted derivatives containing the omega-carboxyalkyl group, the compounds with 6-8 carbon atoms in the side chain were especially effective. The derivatives holding the phenylene group in the side chain exhibited much higher inhibitory activity than those of the alkylene type. Among them, (E)-3-[4-(3-pyridylmethyl)phenyl]-2-methylacrylic acid hydrochloride (5a) had the highest potency (IC50 = 3 x 10(-9) M). The beta-substituted pyridine derivatives and 1-substituted imidazole derivatives which had the same side chain showed almost the same potency. The beta-substituted pyridine derivatives do not inhibit arachidonic acid cyclooxygenase or prostaglandin I2 synthetase, two other enzymes of the arachidonic cascade.
血栓素（TX）合成酶可被吡啶抑制。β-取代吡啶衍生物比具有相同侧链的γ-取代衍生物显示出更高的抑制效力。在含有ω-羧基烷基的β-取代衍生物中，侧链含有6至8个碳原子的化合物尤为有效。侧链带有亚苯基的衍生物比亚烷基型衍生物表现出更高的抑制活性。其中，（E）-3-[4-（3-吡啶基甲基）苯基]-2-甲基丙烯酸盐酸盐（5a）具有最高的效力（IC50 = 3×10^(-9) M）。具有相同侧链的β-取代吡啶衍生物和1-取代咪唑衍生物显示出几乎相同的效力。β-取代吡啶衍生物不抑制花生四烯酸环氧合酶或前列腺素I2合成酶，这是花生四烯酸级联反应中的另外两种酶。
