申请人:Erasmus University Rotterdam Medical Center
公开号:EP4342890A1
公开(公告)日:2024-03-27
The present invention is directed to a scaffold and a compound for targeting fibroblast activation protein (FAP) in cancer-associated fibroblasts (CAFs). The scaffold comprises a (4-quinoinolyl)glycinyl-2-cyanopyrrolidine scaffold that is substituted on the 8th position of the quinoinolyl moiety with a bridging carbon or oxygen atom according to formula (I)
wherein X represents CH2 or O; R1 represents H, Me, CH(CH3)C2H5, CH2CH(CH3)2, CH(CH3)2, CH2OH, CH2SH, CH(OH)CH3, CH2C(O)NH2, CH2CH2C(O)NH2, (CH2)mCO2H, (CH2)mNH2, wherein m is 1-4; and R2 and R3 each independently represent H or F.
本发明旨在针对癌相关成纤维细胞(CAFs)中的成纤维细胞激活蛋白(FAP),提供一种支架和化合物。所述支架包括一个取代在邻醌基部分第8位的(4-邻醌甲基)甘氨酰-2-氰基吡咯烷支架,其上连接有一个桥接碳或氧原子,结构如式(I)所示,其中X代表CH2或O;R1代表H、甲基(Me)、CH(CH3)C2H5、CH2CH(CH3)2、CH(CH3)2、CH2OH、CH2SH、CH(OH)CH3、CH2C(O)NH2、CH2CH2C(O)NH2、(CH2)mCO2H、(CH2)mNH2,其中m为1-4;R2和R3各自独立地代表H或F。