Zorifertinib (AZD3759; AZD-3759; zorifertinibum)

Description: Zorifertinib (formerly AZD3759; AZD-3759; zorifertinibum) is a novel, potent, orally bioavailable, CNS (central nervous system)-penetrant EGFR (epidermal growth factor receptor) inhibitor with potential antitumor activity. It inhibits EGFR (WT), EGFR (L858R), and EGFR (exon 19Del) with IC50s of 0.3 nM, 0.2 nM, and 0.2 nM, respectively. AZD3759 binds to and inhibits the activity of EGFR as well as certain mutant forms of EGFR. This prevents EGFR-mediated signaling, and may lead to both induction of cell death and inhibition of tumor growth in EGFR-overexpressing cells. In summary, AZD3759 is an investigational anticaner drug that is currently in Phase 1 clinical trial, and has excellent central nervous system penetration and which induces profound regression of brain metastases in a mouse model.

References: J Med Chem. 2015 Oct 22; 58(20):8200-15

Chemical Name: (R)-4-((3-chloro-2-fluorophenyl)amino)-7-methoxyquinazolin-6-yl 2, 4-dimethylpiperazine-1-carboxylate

InChi Key: MXDSJQHFFDGFDK-CYBMUJFWSA-N

InChi Code: InChI=1S/C22H23ClFN5O3/c1-13-11-28(2)7-8-29(13)22(30)32-19-9-14-17(10-18(19)31-3)25-12-26-21(14)27-16-6-4-5-15(23)20(16)24/h4-6, 9-10, 12-13H, 7-8, 11H2, 1-3H3, (H, 25, 26, 27)/t13-/m1/s1

SMILES Code: O=C(N1[CH](C)CN(C)CC1)OC2=CC3=C(NC4=CC=CC(Cl)=C4F)N=CN=C3C=C2OC