Journal of Medicinal Chemistry p. 1033 - 1038 (1989)
Update date:2022-08-04
Topics:
DeRuiter, Jack
Swearingen, Blake E.
Wandrekar, Vinay
Mayfield, Charles A.
A number of N-benzoylglycines (6), N-acetyl-N-phenylglycines (7), N-benzoyl-N-phenylglycines (8), and tricyclic N-acetic acids (9-12) were synthesized as analogues of the N-acylglycine-containing aldolase reductase inhibitors alrestatin and 2-oxoquinoline-1-acetic acid.Derivatives of 6, which represent ring-simplified analogues of alrestatin, are very weak inhibitors of aldolase reductase obtained from rat lens, producing 50percent inhibition only at concentrations exceeding 100 μM.Compounds of series 7 were designed as ring-opened analogues of the 2-oxoquinolines.While this derivatives are more potent than compounds of series 6 (IC 50s of 6-80 μM), they are less active than the corresponding 2-oxoquinolines.Analogues of series 8 were designed as hybrid structures of both alrestatin and the 2-oxoquinoline-1-acetic acids.These compounds are substantially more potent than compounds of series 6 and 7 and display inhibitory activities comparable to or greater than alrestatin or the 2-oxoquinolines (IC 50s of 0.1-10 μM).Of the rigid analogues of 8, the most potent derivative is benzoxindol (12) with an IC 50 of 0.67 μM, suggesting that fusion of the two aromatic rings of 8 in a coplanar conformation may optimize affinity for aldose reductase in this series.
View MoreContact:+31-24-3886056
Address:Binderskampweg 29 Unit 36
Tianjin Realet Chemical Technology Co.,Ltd.
website:http://www.realetchem.com
Contact:+86-022-58788819
Address:shuanggang industrial park
Linyi Shengxin Pharmaceutical R&D Co., Ltd
Contact:+86-18653953873
Address:West First of Yufeng Road, Yishui County
Contact:+86-633-8332928
Address:No.1,Huanghai Yilu.Rizhao,Shandong
Luoyang Aoda chemical Co.,Ltd.
Contact:+86-379-67518785 67516588
Address:MiaoWan industry district,YanShi City,Henan,China
Doi:10.1021/jm901215m
(2009)Doi:10.1016/S0040-4020(01)86018-X
(1988)Doi:10.1016/j.tetlet.2009.08.097
(2009)Doi:10.1002/asia.201402924
(2015)Doi:10.1055/s-1988-27675
(1988)Doi:10.1055/s-0029-1217728
(2009)