2-(2-acryloyl-2,6-diazaspiro3.4octan-6-yl)-6-(1H-indazol-4-yl as inhibitor of G12C mutant KRAS protein to inhibit tumor metastasis )-benzonitrile derivatives and related compounds

摘要

The present invention provides an inhibitor of G12C mutant KRAS protein for the treatment of tumor metastasis, for example, 2-(2-acryloyl-2,6-diazaspiro[3.4]octan-6-yl)-6-(1H -Indazol-4-yl)-benzonitrile, for example 2-(2-acryloyl-2,7-diazaspiro[3.5]nonan-7-yl)-6-(1H-indazole-4 -yl)-benzonitrile derivatives, and related compounds of formula (I): The present description provides exemplary compounds (eg pages 53-90; Table 1; compounds I-1 to 1-141), pharmacological data (eg pages 125-128; Table 2; Example 1) and their synthesis (eg pages 129-143; Examples 2-7). Exemplary compounds include, for example, 2-(2-acryloyl-2,6-diazaspiro[3.4]octan-6-yl)-6-(5-methyl-1H-indazol-4-yl)- 4-morpholinobenzonitrile (Example 2; compound I-1) and 6-(2-acryloyl-2,7-diazaspiro[3.5]nonan-7-yl)-3-methoxy-2 -(5-Methyl-1H-indazol-4-yl)-4-morpholinobenzonitrile (Example 7; compound I-84).