Synthesis of Six-membered Ring Analogues of RK-682 and Meldrum’s acid derivatives. Evaluation on the Inhibition of Protein Tyrosine Phosphatases

Synthesis of Six-membered Ring Analogues of RK-682 and Meldrum’s acid derivatives. Evaluation on the Inhibition of Protein Tyrosine Phosphatases

Carneiro, Vânia M. T.; Trivella, Daniela B. B.; Aparicio, Ricardo; Pilli, Ronaldo A.

Abstract:

Protein tyrosine phosphatases (PTPs) together with protein tyrosine kinases (PTKs) regulate protein tyrosine phosphorylation. Their abnormal functions are involved in the initiation and maintenance of the oncogenic state in human. Several synthetic tetronic acid derivatives related to the natural product RK-682 (R)-1 (Figure 1) have been evaluated as inhibitors of dual-specificity phosphatases VHR and CDC-25B and four derivatives were shown to be the most potent inhibitors of CDC-25B described so far. The scope of this work includes the synthesis of sixmembered ring homologues of RK-682 and Meldrum’s acid derivatives and evaluation of their inhibition against human protein tyrosine phosphatases (LMW-PTP, CDC-25B and PTP-1B).

Protein tyrosine phosphatases (PTPs) together with protein tyrosine kinases (PTKs) regulate protein tyrosine phosphorylation. Their abnormal functions are involved in the initiation and maintenance of the oncogenic state in human. Several synthetic tetronic acid derivatives related to the natural product RK-682 (R)-1 (Figure 1) have been evaluated as inhibitors of dual-specificity phosphatases VHR and CDC-25B and four derivatives were shown to be the most potent inhibitors of CDC-25B described so far. The scope of this work includes the synthesis of sixmembered ring homologues of RK-682 and Meldrum’s acid derivatives and evaluation of their inhibition against human protein tyrosine phosphatases (LMW-PTP, CDC-25B and PTP-1B).

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DOI: 10.5151/chempro-15bmos-BMOS2013_201382195919

Referências bibliográficas

• [1] 1 Scott, M. L. et al. Curr. Pharm. Des. 2010, 16, 1843.
• [2] 2 Sodeoka, M. et al. J. Med. Chem. 2001, 44, 3216.
• [3] 3 Pashkovskii, F. S. et al. Russ. J. Org. Chem. 2003, 39, 1060.

Como citar:

Carneiro, Vânia M. T.; Trivella, Daniela B. B.; Aparicio, Ricardo; Pilli, Ronaldo A.; "Synthesis of Six-membered Ring Analogues of RK-682 and Meldrum’s acid derivatives. Evaluation on the Inhibition of Protein Tyrosine Phosphatases", p-60-60. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_201382195919