839705-68-9

Basic information

• Product Name: N-(4-methyl-3-(1-methyl-7-(methylsulfonyl)-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)phenyl)-3-(trifluoromethyl)-benzamide
• Synonyms: N-(4-methyl-3-(1-methyl-7-(methylsulfonyl)-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)phenyl)-3-(trifluoromethyl)-benzamide
• CAS NO: 839705-68-9
• Molecular Weight: 519.504
• Mol File: 839705-68-9.mol
• Article Data: 2

Chemical Properties

• CAS DataBase Reference: N-(4-methyl-3-(1-methyl-7-(methylsulfonyl)-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)phenyl)-3-(trifluoromethyl)-benzamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-(4-methyl-3-(1-methyl-7-(methylsulfonyl)-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)phenyl)-3-(trifluoromethyl)-benzamide(839705-68-9)
• EPA Substance Registry System: N-(4-methyl-3-(1-methyl-7-(methylsulfonyl)-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)phenyl)-3-(trifluoromethyl)-benzamide(839705-68-9)

Safety Data

• Hazardous Substances Data: 839705-68-9(Hazardous Substances Data)

Upstream product

• 221876-21-7 N-(4-methyl-3-nitrophenyl)-3-(trifluoromethyl)benzamide 
• 119-32-4 4-Methyl-3-nitroanilin 
• 1237750-46-7 N-(4-methyl-3-(((4-(methylamino)-2-(methylthio)pyrimidin-5-yl)methyl)amino)phenyl)-3-(trifluoromethyl)benzamide 
• 185040-32-8 4-methylamino-2-methylthiopyrimidine-5-carboxaldehyde 
• 17759-30-7 (4-methylamino-2-methylsulfanyl-pyrimidin-5-yl)-methanol 
• 76360-82-2 4-methylamino-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester 
• 5909-24-0 4-chloro-2-methanesulfanylpyrimidine-5-carboxylic acid ethyl ester 
• 30069-31-9 N-(3-amino-4-methylphenyl)-3-(trifluoromethyl)benzamide 
• 2251-65-2 3-(Trifluoromethyl)benzoyl chloride 
• 1237750-47-8 N-(4-methyl-3-(1-methyl-7-(methylthio)-2-oxo-1,2-dihydropyrimido[4,5-d]pyrimidin-3(4H)-yl)phenyl)-3-(trifluoromethyl)benzamide 

Downstream Products

• 839706-07-9 GNF-7 
• 839708-29-1 GNF-6 
• 839708-13-3 GNF-8 

Relevant articles and documents

Discovery of 2-((3-Amino-4-methylphenyl)amino)-N-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenyl)-4-(methylamino)pyrimidine-5-carboxamide (CHMFL-ABL-053) as a Potent, Selective, and Orally Available BCR-ABL/SRC/p38 Kinase Inhibitor for Chronic Myeloid Leukemia

Starting from a dihydropyrimidopyrimidine core scaffold based compound 27 (GNF-7), we discovered a highly potent (ABL1: IC50 of 70 nM) and selective (S score (1) = 0.02) BCR-ABL inhibitor 18a (CHMFL-ABL-053). Compound 18a did not exhibit apparent inhibitory activity against c-KIT kinase, which is the common target of currently clinically used BCR-ABL inhibitors. Through significant suppression of the BCR-ABL autophosphorylation (EC50 about 100 nM) and downstream mediators such as STAT5, Crkl, and ERK's phosphorylation, 18a inhibited the proliferation of CML cell lines K562 (GI50 = 14 nM), KU812 (GI50 = 25 nM), and MEG-01 (GI50 = 16 nM). A pharmacokinetic study revealed that 18a had over 4 h of half-life and 24% bioavailability in rats. A 50 mg/kg/day dosage treatment could almost completely suppress tumor progression in the K562 cells inoculated xenograft mouse model. As a potential useful drug candidate for CML, 18a is under extensive preclinical safety evaluation now.