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

Molecules

Maria Letícia de Castro Barbosa¹  Thiago José Figueira Ramos¹  Ana Carolina Santos de Arantes¹  Marco Aurélio Martins¹  Patrícia Machado Rodrigues e Silva¹  Eliezer J. Barreiro¹ 

[1] ¹Laboratory 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

关键词: inflammation;    TNF-α;    LASSBio-468;    LASSBio-596;    phthalimide;   

DOI  :  10.3390/molecules171214651

来源: mdpi

【 摘 要 】

In this paper we report the design, synthesis and pharmacological evaluation of a new series of phenyl sulfonamide derivatives 2a–h and 3–8 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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.