175411-12-8

Basic information

• Product Name: Pyrido[3,2-d]pyrimidine-2,4-diamine, 6-[[(2,6-dichlorophenyl)amino]methyl]-
• CAS NO: 175411-12-8
• Molecular Formula: C14H12Cl2N6
• Molecular Weight: 335.195
• Mol File: 175411-12-8.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: Pyrido[3,2-d]pyrimidine-2,4-diamine, 6-[[(2,6-dichlorophenyl)amino]methyl]-(CAS DataBase Reference)
• NIST Chemistry Reference: Pyrido[3,2-d]pyrimidine-2,4-diamine, 6-[[(2,6-dichlorophenyl)amino]methyl]-(175411-12-8)
• EPA Substance Registry System: Pyrido[3,2-d]pyrimidine-2,4-diamine, 6-[[(2,6-dichlorophenyl)amino]methyl]-(175411-12-8)

Safety Data

• Hazardous Substances Data: 175411-12-8(Hazardous Substances Data)

Upstream product

• 76807-54-0 Acetic acid 2,4-dihydroxy-pyrido[3,2-d]pyrimidin-6-ylmethyl ester 
• 76807-53-9 6-Methyl-5-oxy-pyrido[3,2-d]pyrimidine-2,4-diol 
• 76822-61-2 2,4-Diamino-6-(hydroxymethyl)pyrido<3,2-d>pyrimidine 
• 76807-56-2 2,4-diamino-6-(bromomethyl)pyrido<3,2-d>pyrimidine 
• 608-31-1 2,6-Dichloroaniline 
• 2499-96-9 2,4-dioxo-6-methylpyrido<3,2-d>pyrimidine 
• 76807-55-1 6-(Acetoxymethyl)-2,4-dichloropyrido<3,2-d>pyrimidine 

Relevant articles and documents

Nonclassical 2,4-diamino-8-deazafolate analogues as inhibitors of dihydrofolate reductases from rat liver, Pneumocystis carinii, and Toxoplasma gondii

The synthesis and biological activity of 42 6-substituted-2,4- diaminopyrido[3,2-d]pyrimidines (2,4-diamino-8-deazafolate analogues) are reported. The compounds were synthesized in improved yields compared to previous classical analogues using modifications of procedures reported previously by us. Specifically, the S-phenyl-; mono-, di-, and trimethoxyphenyl-; and mono-, di-, and trichlorophenyl-substituted analogues with H or CH3 at the N10 position and methyl and trifluoromethyl phenyl ketone analogues with H, C0H3, and CH2C≡CH at the N10 position were synthesized. The S10 and N10 α- and β-naphthyl analogues along with the N10 CH3 analogues were also synthesized. These compounds were evaluated as inhibitors of dihydrofolate reductases (DHFR) from Pneumocystis carinii (pc) and Toxoplasma gondii (tg); selectivity ratios were determined against rat liver (rl) DHFR as the mammalian reference enzyme. Against pcDHFR the IC50 values ranged from 0.038 x 10-6 M for 2,4-diamino-6-[(N-methyl-2'- naphthylamino)methyl]pyrido[3,2-d]pyrimidine (28) to 5.5 x 10-6 M for 2,4- diamino-6-[(2',4'-dimethoxyanilino)methyl]pyrido[3,2-d]pyrimidine (15). N10 methylation in all instances increased potency. None of the analogues were selective for pcDHFR. Against tgDHFR the most potent analogue was 2,4- diamino-6-[(N-methylanilino)methyl]pyrido[3,2-d]pyrimidine (5) (IC50 0.0084 x 10-6 M) and the least potent was 2,4-diamino-6-[(2'- naphthylamino)methyl]-pyrido[3,2-d]pyrimidine (37) (IC50 0.16 x 10-6 M). N10 methylation afforded an increase in potency up to 10-fold. In contrast to pcDHFR, several of the 8-deaza analogues were significantly selective for tgDHFR, most notably 2,4-diamino-6-[(2'-chloro-N- methylanilino)methyl]pyrido[3,2-d]pyrimidine (13), 2,4-diamino-6-[(3',4',5'- trimethoxyanilino)methyl]pyrido-[3,2-d]pyrimidine (29), and 2,4-diamino-6- [(2',4',6'-trichloroanilino)methyl]pyrido[3,2-d]pyrimidine (32) which combined high potency at 10-8 M along with selectivities of 8.0, 5.0, and 12.4, respectively. The potency of these three analogues are comparable to the clinically used agent trimetrexate while their selectivities for tgDHFR are 17-43-fold better than trimetrexate.