Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response
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 tetraflu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2012-12-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/17/12/14651 |
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| author | Lídia Moreira Lima Eliezer J. Barreiro Marco Aurélio Martins Patrícia Machado Rodrigues e Silva Thiago José Figueira Ramos Ana Carolina Santos de Arantes Maria Letícia de Castro Barbosa |
| author_facet | Lídia Moreira Lima Eliezer J. Barreiro Marco Aurélio Martins Patrícia Machado Rodrigues e Silva Thiago José Figueira Ramos Ana Carolina Santos de Arantes Maria Letícia de Castro Barbosa |
| author_sort | Lídia Moreira Lima |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T10:18:18Z |
| format | Article |
| id | doaj.art-8b16ce12ee7a4efe8c6700c3b4a3a081 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-21T10:18:18Z |
| publishDate | 2012-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8b16ce12ee7a4efe8c6700c3b4a3a0812022-12-21T19:07:32ZengMDPI AGMolecules1420-30492012-12-011712146511467210.3390/molecules171214651Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory ResponseLídia Moreira LimaEliezer J. BarreiroMarco Aurélio MartinsPatrícia Machado Rodrigues e SilvaThiago José Figueira RamosAna Carolina Santos de ArantesMaria Letícia de Castro BarbosaIn this paper we report the design, synthesis and pharmacological evaluation of a new series of phenyl sulfonamide derivatives 2a&#8211;h and 3&#8211;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-&#945; 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.http://www.mdpi.com/1420-3049/17/12/14651inflammationTNF-&#945</keyword> <keyword>LASSBio-468LASSBio-596phthalimide |
| spellingShingle | Lídia Moreira Lima Eliezer J. Barreiro Marco Aurélio Martins Patrícia Machado Rodrigues e Silva Thiago José Figueira Ramos Ana Carolina Santos de Arantes Maria Letícia de Castro Barbosa Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response Molecules inflammation TNF-&#945 </keyword> <keyword>LASSBio-468 LASSBio-596 phthalimide |
| title | Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response |
| title_full | Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response |
| title_fullStr | Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response |
| title_full_unstemmed | Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response |
| title_short | Synthesis and Pharmacological Evaluation of Novel Phenyl Sulfonamide Derivatives Designed as Modulators of Pulmonary Inflammatory Response |
| title_sort | synthesis and pharmacological evaluation of novel phenyl sulfonamide derivatives designed as modulators of pulmonary inflammatory response |
| topic | inflammation TNF-&#945 </keyword> <keyword>LASSBio-468 LASSBio-596 phthalimide |
| url | http://www.mdpi.com/1420-3049/17/12/14651 |
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