Cross P E, Dickinson R P, Parry M J, Randall M J
J Med Chem. 1986 Sep;29(9):1643-50. doi: 10.1021/jm00159a013.
The preparation of a series of 2-(1H-imidazol-1-ylmethyl)-substituted carboxylic acids of benzo[b]furan, benzo-[b]thiophene, indole, and naphthalene is described. All compounds showed a similar level of activity as TxA2 synthetase inhibitors in vitro, having IC50 values between 1 and 7 X 10(-8) M. In the cases examined, compounds had, at most, only negligible activity against PGI2 synthetase, cyclooxygenase, and steroid 11 beta-hydroxylase. The benzo[b]thiophenes generally showed the greatest potency in vivo, and compounds 72, 73, and 75 caused almost complete inhibition of thromboxane production for 6 h after oral administration of 0.5 mg/kg to conscious dogs. In the case of 73 and 75, thromboxane production was still inhibited by 80% after 24 h.
本文描述了一系列2-(1H-咪唑-1-基甲基)取代的苯并[b]呋喃、苯并[b]噻吩、吲哚和萘羧酸的制备方法。所有化合物在体外均表现出与血栓素A2合成酶抑制剂相似的活性水平，IC50值在1至7×10(-8)M之间。在所研究的案例中，化合物对前列环素合成酶、环氧化酶和甾体11β-羟化酶的活性至多可忽略不计。苯并[b]噻吩类化合物在体内通常表现出最强的效力，化合物72、73和75在给清醒犬口服0.5mg/kg后6小时几乎完全抑制了血栓素的产生。就化合物73和75而言，24小时后血栓素的产生仍被抑制80%。
