Boyle E A, Mangan F R, Markwell R E, Smith S A, Thomson M J, Ward R W, Wyman P A
J Med Chem. 1986 Jun;29(6):894-8. doi: 10.1021/jm00156a004.
The synthesis of a series of 7-aroyl-2,3-dihydrobenzo[b]furan-3-carboxylic acids and 7-benzoyl-2,3-dihydrobenzo[b]thiophene-3-carboxylic acids is described. The isomeric 4-benzoyl-1,3-dihydrobenzo[c]furan-1-carboxylic acid was also prepared. Compounds were evaluated for analgesic activity in the mouse phenyl-p-quinone-induced writhing test. Selected compounds were tested for their ability to produce gastric damage in fasted mice and for inhibition of prostaglandin synthetase activity in vitro. Zomepirac was used as a reference. Structure-activity relationships are discussed. One of the compounds, 7-benzoyl-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylic acid (2c), combined potent analgesic activity with low gastric irritancy.
本文描述了一系列7-芳酰基-2,3-二氢苯并[b]呋喃-3-羧酸和7-苯甲酰基-2,3-二氢苯并[b]噻吩-3-羧酸的合成。还制备了异构体4-苯甲酰基-1,3-二氢苯并[c]呋喃-1-羧酸。在小鼠苯醌诱导的扭体试验中对化合物的镇痛活性进行了评估。对选定的化合物进行了禁食小鼠胃损伤产生能力和体外前列腺素合成酶活性抑制的测试。以佐美酸作为对照。讨论了构效关系。其中一种化合物，7-苯甲酰基-5-氯-2,3-二氢苯并[b]呋喃-3-羧酸（2c），兼具强效镇痛活性和低胃刺激性。
