- Autores: Coelho L, Lukens AK, Mazitschek R, Moreira R, Nogueira F, Paulo A, Santos SA, Wirth DF
- Ano de Publicação: 2015
- Journal: Journal of Medicinal Chemistry
- Link: http://www.ncbi.nlm.nih.gov/pubmed/26295174
A series of 3-piperidin-4-yl-1H-indoles with building blohttp://ghtm.ihmt.unl.pt/publications/exploring-the-3-…larial-chemotype/ck diversity was synthesized based on a hit derived from an HTS whole-cell screen against Plasmodium falciparum. Thirty-eight compounds were obtained following a three-step synthetic approach and evaluated for anti-parasitic activity.
The SAR shows that 3-piperidin-4-yl-1H-indole is intolerant to most N-piperidinyl modifications. Nevertheless, we were able to identify a new compound (10d) with lead-like properties (MW = 305; cLogP = 2.42), showing antimalarial activity against drug-resistant and sensitive strains (EC50 values ∼ 3 μM), selectivity for malaria parasite and no cross-resistance with chloroquine, thus representing a potential new chemotype for further optimization towards novel and affordable antimalarial drugs.