Molecules 2012, 17(12), 14651-14672; doi:10.3390/molecules171214651
Article

Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response

1 Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio®), Federal University of Rio de Janeiro, P.O. Box 68024, 21944-971, Rio de Janeiro, RJ, Brazil 2 Graduate Program of Chemistry (PGQu), Chemistry Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-909, RJ, Brazil 3 Laboratory of Inflammation—Oswaldo Cruz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, 21045-900, RJ, Brazil
* Author to whom correspondence should be addressed.
Received: 17 October 2012; in revised form: 19 November 2012 / Accepted: 5 December 2012 / Published: 10 December 2012
(This article belongs to the Section Medicinal Chemistry)
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Abstract: In this paper we report the design, synthesis and pharmacological evaluation of a new series of phenyl sulfonamide derivatives 2ah and 38 planned by structural modification on the anti-inflammatory prototype LASSBio-468 (1). Among the synthesized analogues, the tetrafluorophthalimide LASSBio-1439 (2e) stands out showing an in vitro anti-TNF-α effect similar to the standard thalidomide. The relevance of tetrafluorination of the phthalimide nucleus was also confirmed by the anti-inflammatory profile of 2e, through oral administration, in a murine model of pulmonary inflammation. The corresponding tetrafluorocarboxyamide metabolite LASSBio-1454 (15), generated from partial hydrolysis of the derivative 2e, presented a significant in vitro effect and a pronounced anti-inflammatory activity in vivo.
Keywords: inflammation; TNF-α; LASSBio-468; LASSBio-596; phthalimide

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MDPI and ACS Style

Barbosa, M.L.C.; Ramos, T.J.F.; de Arantes, A.C.S.; Martins, M.A.; Silva, P.M.R.; Barreiro, E.J.; Lima, L.M. Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response. Molecules 2012, 17, 14651-14672.

AMA Style

Barbosa MLC, Ramos TJF, de Arantes ACS, Martins MA, Silva PMR, Barreiro EJ, Lima LM. Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response. Molecules. 2012; 17(12):14651-14672.

Chicago/Turabian Style

Barbosa, Maria L.C.; Ramos, Thiago J.F.; de Arantes, Ana C.S.; Martins, Marco A.; Silva, Patrícia M.R.; Barreiro, Eliezer J.; Lima, Lídia M. 2012. "Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response." Molecules 17, no. 12: 14651-14672.

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