ChemInform Abstract: Nonclassical 2,4-Diamino-5-aryl-6-ethylpyrimidine Antifolates: Activity as Inhibitors of Dihydrofolate Reductase from Pneumocystis carinii and Toxoplasma gondii and as Antitumor Agents.

✍ Scribed by C. ROBSON; M. A. MEEK; J.-D. GRUNWALDT; P. A. LAMBERT; S. F. QUEENER; D. SCHMIDT; R. J. GRIFFIN

• Publisher: John Wiley and Sons
• Year: 2010
• Weight: 33 KB
• Volume: 29
• Category: Article
• ISSN: 0931-7597
• DOI: 10.1002/chin.199801174

✦ Synopsis

Nonclassical 2,4-Diamino-5-aryl-6-ethylpyrimidine Antifolates: Activity as Inhibitors of Dihydrofolate Reductase from Pneumocystis carinii and Toxoplasma gondii and as Antitumor Agents.

-Title compounds such as (I) exhibit potent inhibitory activity against dihydrofolate reductase (DHFR) from Toxoplasma gondii, especially compound (Ia), but are generally weak inhibitors of DHFR from Pneumocystis carinii with no selectivity. Evaluation of some title compounds for in vivo antitumor activity reveals that compound (Ic) combines significant antitumor activity with minimal toxicity. In contrast to its chloro analogue, which gives poor product yields due to vigorous reaction conditions, reaction of fluoro compound (II) with corresponding amines, e.g. (III), affords the target compounds, e.g. (Ia), (Id), and (Ie), in good to excellent yields. -(ROBSON, C.; MEEK, M. A.;