Cawrse, Brian M.; Lapidus, Rena S.; Cooper, Brandon; Choi, Eun Yong; Seley-Radtke, Katherine L. published an article in 2018, the title of the article was Anticancer Properties of Halogenated Pyrrolo[3,2-d]pyrimidines with Decreased Toxicity via N5 Substitution.Synthetic Route of 626-48-2 And the article contains the following content:
Halogenated pyrrolo[3,2-d]pyrimidine analogs have shown antiproliferative activity in recent studies, with cell accumulation occurring in the G2/M stage without apoptosis. However, the mechanism of action and pharmacokinetic (PK) profile of these compounds has yet to be determined To investigate the PK profile of these compounds, a series of halogenated pyrrolo[3,2-d]pyrimidine compounds was synthesized and first tested for activity in various cancer cell lines followed by a mouse model. EC50 values ranged from 0.014 to 14.5 μM, and maximum tolerated doses (MTD) in mice were between 5 and 10 mg kg-1. This indicates a wide variance in activity and toxicity that necessitates further study. To decrease toxicity, a second series of compounds was synthesized with N5-alkyl substitutions in an effort to slow the rate of metabolism, which was thought to be leading to the toxicity. The N-substituted compounds demonstrated comparable cell line activity (EC50 values between 0.83-7.3 μM) with significantly decreased toxicity (MTD=40 mg kg-1). Finally, the PK profile of the active N5-substituted compound shows a plasma half-life of 32.7 min, and rapid conversion into the parent unsubstituted analog. Together, these data indicate that halogenated pyrrolo[3,2-d]pyrimidines present a promising lead into potent antiproliferative agents with tunable activity and toxicity, and rapid metabolism The experimental process involved the reaction of 6-Methylpyrimidine-2,4(1H,3H)-dione(cas: 626-48-2).Synthetic Route of 626-48-2
The Article related to antitumor halogenated pyrrolo pyrimidine preparation toxicity pharmacokinetics prodrug, anticancer, antiproliferative, prodrugs, pyrrolopyrimidines, triple-negative breast cancer and other aspects.Synthetic Route of 626-48-2
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia