By repurposing a typical dopamine D1/D5 receptor agonist motif, C1-substituted-N3-benzazepine or benzazecine, into the classical RTK inhibitor 2,4-diaminopyrimidine skeleton, a series of new 2,4-diarylaminopyrimidine analogues (DAAPalogues) were developed. Compounds 7 and 8a were identified possessing high potency against both c-Met and ALK kinases. Compound 8a displayed appreciable antitumor efficacy at the dose of 1 mg/kg in the ALK-driven BF3/EML4-ALK xenograft mice model.
- 2,4-diarylaminopyrimidine analogues
- C1-Substituted- N 3-benzazepine
- c-Met/ALK dual inhibitor
- structure repurposing
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry