Recent progress in the medicinal chemistry of 2,4-diaminopyrimidines.

  title={Recent progress in the medicinal chemistry of 2,4-diaminopyrimidines.},
  author={Barbara Roth and C. C. Cheng},
  journal={Progress in medicinal chemistry},
  • B. Roth, C. Cheng
  • Published 1982
  • Biology, Chemistry
  • Progress in medicinal chemistry

Chemistry and biological activity of antifolates.

  • A. Rosowsky
  • Chemistry
    Progress in medicinal chemistry
  • 1989

The medicinal chemistry of the azido group.

  • R. Griffin
  • Chemistry, Biology
    Progress in medicinal chemistry
  • 1994

Trimethoprim and other nonclassical antifolates an excellent template for searching modifications of dihydrofolate reductase enzyme inhibitors

An excellent review of DHFR inhibition and their relevance to antimicrobial and parasitic chemotherapy was presented and advances in design, synthesis, and biological evaluations in structural modifications of TMP as DHFR inhibitors are highlighted.

Design, synthesis, docking and in vitro antifungal study of 1,2,4-triazole hybrids of 2-(aryloxy)quinolines

Abstract Substituted quinolines containing a 1,2,4-triazole moiety were synthesized using reported methods. The molecular docking studies support the experimental results that these compounds are

Thymidylate synthase inhibitors.

2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 13. Some alkenyl derivatives with high in vitro activity against anaerobic organisms.

The 3,5-bis(1-propenyl)-4-methoxy derivative 8 was 1 order of magnitude more active against Escherichia coli dihydrofolate reductase than its saturated counterpart, and it was also more active than trimethoprim, however, it was considerably less active in vitro against the Gram-negative organisms.

Synthesis, antimicrobial activity and molecular modeling study of substituted 5-aryl-pyrimido[5,4-c]quinoline-2,4-diones

Results of the antimicrobial screening showed that compounds 5d, 5e, 5f, 5h and 5k have broad-spectrum antibacterial efficacy being moderately active against all the tested Gram +ve and two Gram −ve bacteria.

Synthesis and antibacterial evaluation of new azo-pyrimidine derivatives

  • M. Abdelgawad
  • Chemistry, Biology
    Journal of Applied Pharmaceutical Science
  • 2019
Two new synthesized azo-compounds showed weak (III b) to strong (IV b) antibacterial activity and the molecular operating environment docking program was used for the prediction of the compound IV b action mechanism.



Antimalarial activity of some novel derivatives of 2,4-diamino-5(p-chlorophenyl)-6-ethylpyrimidine (pyrimethamine).

: Thirteen new analogs of 2,4-diamino-5(p-chlorophenyl)-6-ethylpyrimidine (Daraprim, pyrimethamine) in which the alph position of the 6-ethyl substituent was modified were prepared. The respective

Some pyrimidines of biological and medicinal interest. I.

  • C. Cheng
  • Chemistry, Biology
    Progress in medicinal chemistry
  • 1969

5-(1-Adamantyl) pyrimidines as inhibitors of folate metabolism.

It appears that the adamantyl group in position 5 greatly facilitates the passage of pyrimidines through the plasma membrane of the cells, thereby increasing the inhibitory potency of these compounds in cellular systems over and above that expected from enzyme inhibition analysis.



The very strong affinity of 4-amino-4-deoxy analogues ( I and 11) of folic acid ( H I ) for dihydrofolic reductase,l-:’ which has been described as “stoichiometric” or “pseudoirreversible” inhibition

2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 2. C-Alkylation of pyrimidines with Mannich bases and application to the synthesis of trimethoprim and analogues.

A new route to 5-(p-hydroxybenzyl)pyrimidine has been developed which utilizes phenolic Mannich bases plus pyrimidines containing at least two activating groups, and has been used to prepare trimethoprim, a broad-spectrum antibacterial agent.

Quinazolines as inhibitors of dihydrofolate reductase. 4. Classical analogues of folic and isofolic acids.

A series of classical quinazoline analogues of folic and isofolic acids was evaluated for inhibitory activity against the dihydrofolate reductases from rat liver and from Streptococcus faecium, showing modest activity against L1210 leukemia in mice.

Studies on the 2,4-diamino-6-substituted quinazolines. III. The capacity of sulfadiazine to enhance the activities of WR-158,122 and WR-159,412 against infections with various drug-susceptible and drug-resistant strains of Plasmodium falciparum and Plasmodium vivax in owl monkeys.

Application of these combinations prevented emergence of parasites resistant to WR-158,122 or WR-159,412, but did not abolish the differences in effectiveness of either compound against infections with pyrimethamine-susceptible and pyrimetic-resistant strains; however, activities against infection with either susceptible or resistant strains were enhanced markedly.


It soon became evident that not only the halogenated antifolatcs, but also the nonhalogenated parent compounds, could undergo metabolic alteration in some mammalian species; the susceptibility to such alteration.

Quinazolines as inhibitors of dihydrofolate reductase. 3. Analogs of pteroic and isopteroic acids.

A series of 19 quinazoline analogs of pteroic and isopteroic acid was prepared with particular emphasis being placed upon carboxylic acid esters, with several of the more potent inhibitors found to be inactive against L1210 leukemia in mice at low dose levels and were lethal to mice at 100 mg/kg.