Design and Synthesis of New Phosphoramidates Chloroquine Analogs

Design and Synthesis of New Phosphoramidates Chloroquine Analogs

Pedrosa, Leandro F.; Furtado, Antônia C. R.; Machado, Carolina T.; Baêsso, Raphaela de M.; Bastos, Neidemar de M. S.; Macedo, William P. de; Souza, Marcos C.

Abstract:

About 3.3 billion people - half of the world's population - are at risk of malaria. Every year, this leads to about 250 million malaria cases and nearly one million deaths. Therefore, there is urgency to develop new affordable, safe, and efficacious antimalarilas. Although the resistance to chloroquine (CQ) and related 4-aminoquinoline antimalarial drugs has emerged; designing new antimalarial based on the quinoline pharmacophore has distinct advantages due to unique pharmacological effect of 4- aminoquinoline drugs. Several studies demonstrated that various structurally diverse modifications in the side chain of CQ were well tolerated for the antimalarial activity. Systematic variation of the branching and basicity of the side chain of CQ yielded the new 4- aminoquinoline derivatives exhibiting excellent potency against CQ-sensitive and CQ-resistant strains. A new class of Chloroquine analogs containing phosphoramidate group and different alkyl spacer (Figure 1) was structurally planned by modification of side-chain based on the previously described.

About 3.3 billion people - half of the world's population - are at risk of malaria. Every year, this leads to about 250 million malaria cases and nearly one million deaths. Therefore, there is urgency to develop new affordable, safe, and efficacious antimalarilas. Although the resistance to chloroquine (CQ) and related 4-aminoquinoline antimalarial drugs has emerged; designing new antimalarial based on the quinoline pharmacophore has distinct advantages due to unique pharmacological effect of 4- aminoquinoline drugs. Several studies demonstrated that various structurally diverse modifications in the side chain of CQ were well tolerated for the antimalarial activity. Systematic variation of the branching and basicity of the side chain of CQ yielded the new 4- aminoquinoline derivatives exhibiting excellent potency against CQ-sensitive and CQ-resistant strains. A new class of Chloroquine analogs containing phosphoramidate group and different alkyl spacer (Figure 1) was structurally planned by modification of side-chain based on the previously described.

Palavras-chave:

DOI: 10.5151/chempro-14bmos-R0213-2

Referências bibliográficas

• [1] 1 WHO, World malaria report: 2010.
• [2] 2 Kumar, A.; et al., Bioorg. Med. Chem. Lett., 2010, 20, 7059.
• [3] 3 Yearick, K.; et al., J. Med. Chem., 2008, 51 (7), 1995.
• [4] 4 Souza, M. C.; et al., Phosphorus, Sulfur, and Silicon, 2006, 181, 1885.

Como citar:

Pedrosa, Leandro F.; Furtado, Antônia C. R.; Machado, Carolina T.; Baêsso, Raphaela de M.; Bastos, Neidemar de M. S.; Macedo, William P. de; Souza, Marcos C.; "Design and Synthesis of New Phosphoramidates Chloroquine Analogs", p-213-213. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 1, Setembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-14bmos-R0213-2