1.
Bioorg Med Chem
; 25(24): 6563-6580, 2017 12 15.
Artigo
em Inglês
| MEDLINE
| ID: mdl-29133033
RESUMO
A series of A-ring-modified lamellarin N analogues were designed, synthesized, and evaluated as potential noncovalent inhibitors of the EGFR T790M/L858R mutant, a causal factor in the drug-resistant non-small cell lung cancer. Several water-soluble ammonium- or guanidinium-tethered analogues exhibited good kinase inhibitory activities. The most promising analogue, 14f, displayed an excellent inhibitory profile against the T790M/L858R mutant [IC50 (WT)â¯=â¯31.8â¯nM; IC50 (T790M/L858R)â¯=â¯8.9â¯nM]. The effects of A-ring-substituents on activity were rationalized by docking studies.