Synthesis and pharmacological evaluation of N-phenyl-acetamide sulfonamides designed as novel non-hepatotoxic analgesic candidates

Barbosa, Maria Letícia de Castro; Melo, Gabriela Muniz de Albuquerque; Silva, Yolanda Karla Cupertino da; Lopes, Raquel de Oliveira; Souza, Everton Tenório de; Queiroz, Aline Cavalcanti de; Smaniotto, Salete; Alexandre-Moreira, Magna Suzana; Barreiro, Eliezer J.; Lima, Lı́dia Moreira

doi:10.1016/j.ejmech.2009.02.026

Cited by 18 publications

(6 citation statements)

References 29 publications

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“…The organic layer was then dried over anhydrous Na 2 SO 4 , filtered and concentrated at reduced pressure to give the title compound as a yellow powder, 65% yield, mp 207–209 °C. The melting point, 1 H-NMR, 13 C-NMR and IR data for compound 7 are in agreement with previous reports [ 15 ]. 1 H-NMR (200 MHz, DMSO- d 6 , TMS) δ (ppm): 2.09 (s, 3H, COC H 3 ); 2.65 (t, 4H, J = 5.0 Hz, H2' and H6'); 3.16 (t, 4H, J = 5.0 Hz, H3' and H5'); 7.67 (d, 2H, J = 8.9 Hz, H2 and H6); 7.82 (d, 2H, J = 8.9 Hz, H3 and H5); 10.40 (s, 1H, CON H ).…”

Section: Methodssupporting

confidence: 92%

“…The acetylation of aniline ( 10 ) with acetic anhydride provided acetanilide ( 11 ) in 90% yield [ 14 , 15 ]. The second step in the synthesis of 8 was based on a regioselective electrophilic aromatic substitution employing chlorosulfonic acid, giving 12 in 85% yield [ 16 , 17 ].…”

Section: Resultsmentioning

confidence: 99%

“…The second step in the synthesis of 8 was based on a regioselective electrophilic aromatic substitution employing chlorosulfonic acid, giving 12 in 85% yield [ 16 , 17 ]. With this intermediate in hand, the acetamide LASSBio-1295 ( 7 ) was synthesized in 65% yield by condensation of the 4-(acetylamino)benzenesulfonyl chloride ( 12 ) with thiomorpholine [ 15 , 18 ]. The key intermediate 8 was obtained in 93% yield through alkaline hydrolysis of the acetamide 7 ( Scheme 3 ) [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2012

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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.

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Section: Methodssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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

et al. 2012

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“…30 Four other arylsulfonyl chlorides were reacted with piperazine to obtain the arylsulfonyl piperazine right hand fragments needed to assemble analogs.…”

Section: Chemistrymentioning

confidence: 99%

“…29 The piperazine fragment 3 was obtained in high yield from the reaction of p-fluorobenzenesulfonyl chloride with excess piperazine (Scheme 3). 30 Four other arylsulfonyl chlorides were reacted with piperazine to obtain the arylsulfonylpiperazine right-hand fragments needed to assemble analogues.…”

Section: ■ Chemistrymentioning

confidence: 99%

Structure–Activity Relationship Studies of Sulfonylpiperazine Analogues as Novel Negative Allosteric Modulators of Human Neuronal Nicotinic Receptors

et al. 2011

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Neuronal nicotinic receptors have been implicated in several diseases and disorders such as: autism, Alzheimer’s disease, Parkinson’s disease, epilepsy, and various forms of addiction. To understand the role of nicotinic receptors in these conditions, it would be beneficial to have selective molecules that target specific nicotinic receptors in vitro and in vivo. Our laboratory has previously identified novel negative allosteric modulators of human α4β2 (Hα4β2) and human α3β4 (Hα3β4) nicotinic receptors. In the following studies, the effects of novel sulfonylpiperazine analogs that act as negative allosteric modulators on both Hα4β2 nAChRs and Hα3β4 nAChRs were investigated. This work, through structure-activity relationship (SAR) studies, describes the chemical features of these molecules that are important for both potency and selectivity on Hα4β2 nAChRs.

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Synthesis and Pharmacological Evaluation of New Chemical Entities Based on Paracetamol and Their Ibuprofen Conjugates as Novel and Superior Analgesic and Anti-Inflammatory Candidates

et al. 2014

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Synthesis and pharmacological evaluation of N-phenyl-acetamide sulfonamides designed as novel non-hepatotoxic analgesic candidates

Cited by 18 publications

References 29 publications

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

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

Structure–Activity Relationship Studies of Sulfonylpiperazine Analogues as Novel Negative Allosteric Modulators of Human Neuronal Nicotinic Receptors

Synthesis and Pharmacological Evaluation of New Chemical Entities Based on Paracetamol and Their Ibuprofen Conjugates as Novel and Superior Analgesic and Anti-Inflammatory Candidates

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