一些新型取代喹啉-4-酮和1,7-萘啶-4-酮类似物的合成及其抗肿瘤活性

Synthesis and antitumor activity of some new substituted quinolin-4-one and 1,7-naphthyridin-4-one analogs.

作者信息

el-Subbagh H I, Abadi A H, al-Khawad I E, al-Rashood K A

机构信息

Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

出版信息

Arch Pharm (Weinheim). 1999 Jan;332(1):19-24. doi: 10.1002/(sici)1521-4184(19991)332:1<19::aid-ardp19>3.0.co;2-m.

DOI:10.1002/(sici)1521-4184(19991)332:1<19::aid-ardp19>3.0.co;2-m

PMID:10073140

Abstract

The synthesis of some new analogs of quinolin-4-one and 1,7-naphthyridin-4-one is described. The prepared compounds were tested for their in vitro antitumor and cdc2 kinase or cdc25 phosphatase inhibitory activity. Compound ethyl 7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de][2,3-b]pyrido-1,4-thiazine-6-carboxylate (6b) showed antitumor activity against CNS SNB-75, breast T-47D, and lung NCI-H522 cancer cell lines with GI50 values of 8.3, 17.6, and 22.7 microM, respectively. Meanwhile, the compounds ethyl 4-oxo-8-phenylthio-1H,4H-quinoline-3-carboxylate (11a) and 4-oxo-8-phenylthio-1H,4H-1,7-naphthyridine-3-carboxylic acid (12b) have proved to be cdc25 phosphatase inhibitors at IC50 values of 11 and 5 microM, respectively.

摘要

描述了一些喹啉 - 4 - 酮和1,7 - 萘啶 - 4 - 酮新类似物的合成。对所制备的化合物进行了体外抗肿瘤以及cdc2激酶或cdc25磷酸酶抑制活性测试。化合物7 - 氧代 - 2,3 - 二氢 - 7H - 吡啶并[1,2,3 - de][2,3 - b]吡啶并 - 1,4 - 噻嗪 - 6 - 羧酸乙酯（6b）对中枢神经系统SNB - 75、乳腺T - 47D和肺NCI - H522癌细胞系显示出抗肿瘤活性，其GI50值分别为8.3、17.6和22.7 microM。同时，化合物4 - 氧代 - 8 - 苯硫基 - 1H，4H - 喹啉 - 3 - 羧酸乙酯（11a）和4 - 氧代 - 8 - 苯硫基 - 1H，4H - 1,7 - 萘啶 - 3 - 羧酸（12b）已被证明分别是cdc25磷酸酶抑制剂，IC50值为11和5 microM。