1363160-91-1

Basic information

• Product Name: N-(3-(7-(4-(dimethylamino)-2-methoxyphenylamino)-3-methyl-2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidin-1(2H)-yl)phenyl)acrylamide
• CAS NO: 1363160-91-1
• Molecular Weight: 473.534
• Mol File: 1363160-91-1.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: N-(3-(7-(4-(dimethylamino)-2-methoxyphenylamino)-3-methyl-2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidin-1(2H)-yl)phenyl)acrylamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(3-(7-(4-(dimethylamino)-2-methoxyphenylamino)-3-methyl-2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidin-1(2H)-yl)phenyl)acrylamide(1363160-91-1)
• EPA Substance Registry System: N-(3-(7-(4-(dimethylamino)-2-methoxyphenylamino)-3-methyl-2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidin-1(2H)-yl)phenyl)acrylamide(1363160-91-1)

Safety Data

• Hazardous Substances Data: 1363160-91-1(Hazardous Substances Data)

Upstream product

• 7474-82-0 3-methoxy-N¹,N¹-dimethylbenzene-1,4-diamine 
• 68621-88-5 (3-aminophenyl)carbamic acid tert-butyl ester 
• 5909-24-0 4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester 
• 1363161-19-6 tert-butyl 3-(3-methyl-7-(methylsulfonyl)-2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidin-1(2H)-yl)phenylcarbamate 
• 814-68-6 acryloyl chloride 
• 1363161-16-3 tert-butyl 3-(5-(formyl)-2-(methylmercapto)pyrimidine-4-ylamino)phenylcarbamate 
• 1363161-15-2 tert-butyl 3-(5-(hydroxymethyl)-2-(methylmercapto)pyrimidine-4-ylamino)phenylcarbamate 
• 1363161-14-1 ethyl 4-((3-((tert-butoxycarbonyl)amino)phenyl)amino)-2-(methylthio)pyrimidine-5-carboxylate 
• 1363161-18-5 tert-butyl 3-(3-methyl-7-(methylthio)-2-oxo-3,4-dihydropyrimido[4,5-d] pyrimidin-1(2H)-yl) phenylcarbamate 

Relevant articles and documents

PYRIMIDOPYRIMIDONE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF

A compound of formula (I) or (II) and use of the compound in the preparation of drugs for treating cancer are disclosed. The study shows that the compounds can inhibit the growth of many kinds of tumor cells, can be used for targeting epidermal growth factor receptor (EGFR), and particularly can inhibit tumor cells with single or multiple mutations of EGFR (T790M). Therefore, the compound can be used as EGFR inhibitor to treat cancer and has a relatively large application value.

Design, synthesis, and biological evaluation of novel conformationally constrained inhibitors targeting epidermal growth factor receptor threonine 790 → methionine790 mutant

The EGFRT790M mutant contributes approximately 50% to clinically acquired resistance against gefitinib or erlotinib. However, almost all the single agent clinical trials of the second generation irreversible EGFR inhibitors appear inadequate to overcome the EGFRT790M-related resistance. We have designed and synthesized a series of 2-oxo-3,4- dihydropyrimido[4,5-d]pyrimidinyl derivatives as novel EGFR inhibitors. The most potent compounds, 2q and 2s, inhibited the enzymatic activities of wild-type and mutated EGFRs, with IC50 values in subnanomolar ranges, including the T790M mutants. The kinase inhibitory efficiencies of the compounds were further validated by Western blot analysis of the activation of EGFR and downstream signaling in cancer cells harboring different mutants of EGFR. The compounds also strongly inhibited the proliferation of H1975 non small cell lung cancer cells bearing EGFRL858R/T790M, while being significantly less toxic to normal cells. Moreover, 2s displayed promising anticancer efficacy in a human NSCLC (H1975) xenograft nude mouse model.