1236291-32-9Relevant articles and documents
Synthesis and structure-activity relationship of 6-arylureido-3-pyrrol-2- ylmethylideneindolin-2-one derivatives as potent receptor tyrosine kinase inhibitors
Khanwelkar, Rahul R.,Chen, Grace Shiahuy,Wang, Hsiao-Chun,Yu, Chao-Wu,Huang, Chiung-Hua,Lee, On,Chen, Chih-Hung,Hwang, Chrong-Shiong,Ko, Ching-Huai,Chou, Nien-Tzu,Lin, Mai-Wei,Wang, Ling-Mei,Chen, Yen-Chun,Hseu, Tzong-Hsiung,Chang, Chia-Ni,Hsu, Hui-Chun,Lin, Hui-Chi,Shih, Ying-Chu,Chou, Shuen-Hsiang,Tseng, Hsiang-Wen,Liu, Chih-Peng,Tu, Chia-Mu,Hu, Tsan-Lin,Tsai, Yuan-Jang,Chern, Ji-Wang
experimental part, p. 4674 - 4686 (2010/08/06)
A series of new ureidoindolin-2-one derivatives were synthesized and evaluated as inhibitors of receptor tyrosine kinases. Investigation of structure-activity relationships at positions 5, 6, and 7 of the oxindole skeleton led to the identification of 6-ureido-substituted 3-pyrrolemethylidene- 2-oxindole derivatives that potently inhibited both the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) families of receptor tyrosine kinases. Several derivatives showed potency against the PDGFR inhibiting both its enzymatic and cellular functions in the single-digit nanomolar range. Among them, compound 35 was a potent inhibitor against tyrosine kinases, including VEGFR and PDGFR families, as well as Aurora kinases. Inhibitor 36 (non-substituted on the pyrrole or phenyl ring) had a moderate pharmacokinetic profile and completely inhibited tumor growth initiated with the myeloid leukemia cell line, MV4-11, in a subcutaneous xenograft model in BALB/c nude mice.
