Li, Ruoxi; Ling, Dazheng; Tang, Tongke; Huang, Zhenghui; Wang, Manjiong; Mao, Fei; Zhu, Jin; Jiang, Lubin; Li, Jian; Li, Xiaokang published the artcile< Repurposing of antitumor drug candidate Quisinostat lead to novel spirocyclic antimalarial agents>, Safety of Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is pyrimidine containing spirocyclic linker preparation cytotoxicity antimalarial human SAR.
Herein, 30 novel spirocyclic linker derivatives I [R = Ph, N-Me-indolin-2-yl, N-Me-6-F-indolin-3-yl, etc.] were designed and synthesized based on Quisinostat as lead compound and then evaluated for their antimalarial activities and cytotoxicity. Among them, compounds I [R = N-Me-indolin-2-yl, N-Me-6-F-indolin-3-yl] could effectively eliminate wild-type and multi-drug resistant P. falciparum parasites, and display weakened cytotoxicity and good metabolic stability. Western blot assay demonstrated that they could inhibit Plasmodium falciparum histone deacetylase (PfHDAC) activity like Quisinostat. In addition, both I [R = N-Me-indolin-2-yl, N-Me-6-F-indolin-3-yl] showed certain antimalarial efficacy in rodent malaria model, and the animal toxicity of I [R = N-Me-indolin-2-yl] was significantly improved compared with Quisinostat. Overall, I [R = N-Me-indolin-2-yl, N-Me-6-F-indolin-3-yl] were structurally novel PfHDAC inhibitors and provided prospective prototype for further antimalarial drug research.
Chinese Chemical Letters published new progress about Antimalarials. 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Safety of Ethyl 2-chloropyrimidine-5-carboxylate.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia