WZ4002

WZ4002 is a mutant selective EGFR inhibitor with IC50s of 2, 8, 3 and 2 nM for EGFRL858R, EGFRL858R/T790M, EGFRE746_A750 and EGFRE746_A750/T790M, respectively.

WZ4002 is a pyrimidine compound having a 2-methoxy-4-(4-methylpiperazin-1-yl)anilino group at the 2-position, a 3-(acryloylamino)phenoxy group at the 4-position, and a chloro substituent at the 5-position. It has a role as a tyrosine kinase inhibitor and an antineoplastic agent. It is a member of pyrimidines, a member of piperazines and an organochlorine compound.

General procedure: Acryloyl chloride (60 µL, 0.68 mmol) was added dropwise to a solution of amine 4, 14 or 25 (300 mg, 0.68 mmol) and diisopropyethylamine (120 µL, 0.68 mmol) in dichloromethane (10 mL) at 0 °C. The reaction was stirred for 2 h. Then water (10 mL) was added to the reaction mixture and extracted three times with dichloromethane (3 x 6 mL). The combined organic extracts was dried over anhydrous sodium sulfate and concentrated to give a pale white solid. The crude product was purified by flash column chromatography using dichloromethane-methanol (98:2) to obtain the pure acrylamide 1, 2 or 23 as white solids in yields ranging from 31 - 36percent.

A novel mutant-selective EGFR kinase inhibitor of EGFRL858R and EGFRL858R/T790M with IC50s of 2 nM and 8 nM, respectively.

Molecular Weight:495.0
XLogP3:4.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:8
Rotatable Bond Count:8
Exact Mass:494.1833164
Monoisotopic Mass:494.1833164
Topological Polar Surface Area:91.8
Heavy Atom Count:35
Complexity:694
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes