Pentacyclic thiazole indolone sulfonyl piperazine derivative and application thereof

Abstract

The invention relates to a pentacyclic thiazole indolone sulfonyl piperazine derivative and application thereof. According to the synthesis of the derivative, ethyl cyanoacetate is used as a starting raw material, and a hydroxylamine compound (1) is generated under the synergistic effect of sodium nitrite and phosphoric acid; 2-amino ethyl cyanoacetate (2) is obtained through reduction, and then the 2-amino ethyl cyanoacetate (2) reacts with acetic anhydride and a Lawson reagent in sequence to obtain a 5-amino-4-formate thiazole compound (4); the preparation method comprises the following steps: reacting pyrimidino [1 ', 2': 1, 2] pyridino [3, 4-b] indole-4 (12H)-ketone (6) with 2-bromo-6, 7-thiazolo [5 ', 4': 4 ', 5'] pyrimidino [1 ', 2': 1, 2] pyridino [3, 4-b] indole-4 (12H)-ketone (6) through NBS bromination under the catalytic action of phosphorus oxychloride, reacting with Boc piperazine under the alkaline condition, and removing Boc protection to obtain a compound (8); finally, the pentacyclic thiazole indolone sulfonyl piperazine compound 9a-9ab with 28 structures is synthesized by reacting the pentacyclic thiazole indolone sulfonyl piperazine compound 9a-9ab with sulfonyl chloride, and the 28 compounds are investigated to have inhibitory activity on Hela cervical cancer cells, HT-29 human colon cancer cells and HGC-27 human gastric cancer cells.