Key Laboratary of Original New Drugs Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China.
Arch Pharm (Weinheim). 2013 Jul;346(7):521-33. doi: 10.1002/ardp.201300029. Epub 2013 Jun 17.
A series of 4-(2-fluorophenoxy)quinoline derivatives bearing the 4-oxo-1,4-dihydroquinoline-3-carboxamide moiety were designed, synthesized, and evaluated for their in vitro antitumor activity against the H460, HT-29, MKN-45, U87MG, and SMMC-7721 cancer cell lines. Most of the tested compounds showed potent activity and high selectivity toward the HT-29 and MKN-45 cell lines. Furthermore, compounds 21b, 21c, and 21i were further examined for their c-Met kinase activity and exhibited strong efficacy with IC50 values in the single-digit nanomolar range, which was comparable with the positive control foretinib. The most promising compound 21c showed excellent cytostatic activity with IC50 values from 0.01 to 0.53 µM against all tested cell lines, thus being 1.7-2.2 times more active than foretinib.
设计、合成了一系列含有 4-氧代-1,4-二氢喹啉-3-甲酰胺部分的 4-(2-氟苯氧基)喹啉衍生物，并评估了它们对 H460、HT-29、MKN-45、U87MG 和 SMMC-7721 癌细胞系的体外抗肿瘤活性。大多数测试的化合物对 HT-29 和 MKN-45 细胞系表现出强大的活性和高选择性。此外，化合物 21b、21c 和 21i 进一步被检测其 c-Met 激酶活性，表现出与阳性对照物 foretinib 相当的强效力，IC50 值在个位数纳摩尔范围内。最有前途的化合物 21c 对所有测试的细胞系均表现出优异的细胞生长抑制活性，IC50 值在 0.01 至 0.53 μM 之间，因此比 foretinib 活性高 1.7-2.2 倍。
