Regioselectively controlled synthesis of 3(5)-(trifluoromethyl)pyrazolylbenzenesulfonamides and their effects on a pathological pain model in mice

Lobo, Marcio M.; Oliveira, Sara Marchesan; Brusco, Indiara; Machado, Pablo; Timmers, Luís Fernando Saraiva Macedo; Souza, Osmar Norberto de; Martins, Marcos A. P.; Bonacorso, Hélio G.; Santos, Josiane M. dos; Canova, Bruna; Silva, Thiago V.F. da; Zanatta, Nilo

doi:10.1016/j.ejmech.2015.07.036

Cited by 25 publications

(9 citation statements)

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“…Substrates adorned with a substituent flanking the α‐position of styrene ( 14 – 26 ) as well as alkenes bearing polycyclic aromatic hydrocarbons ( 27 , 28 ) and heterocyclic systems 29 – 31 ( 31 including SC‐XRD), all gave the desired trifluoroacylated adducts. Similarly, the key precursors ( 32 , 33 and 34 ) of most recognized anti‐inflammatory drugs bearing trifluoromethylated pyrazole moieties such as Mavacoxib, Celecoxib, and SC‐560[ 52 , 53 , 54 , 55 ] were all synthesized using this photoredox protocol in satisfactory yields. In most cases, we were unable to observe trifluoromethylated or difunctionalized alkene adducts.…”

Section: Resultsmentioning

confidence: 99%

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

et al. 2021

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Section: Resultsmentioning

confidence: 99%

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

et al. 2021

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“…Aryl substituted olefines containing both electron donating and electron withdrawing common functional groups at ortho-, meta-a nd para-positions were successfully trifluoroacylated in 40-85 %i solated yields.I ti s noteworthy that halogen substituents (3,5,6,9,12)and ester (7)groups remained untouched under the reaction conditions, allowing further structural elaboration besides the trifluoroacetyl group.A lkene building blocks including di-and trisubstituted aryl substrates (9-13)furnished the corresponding unsaturated ketones in 76-94 %c hemical yields.S ubstrates adorned with asubstituent flanking the a-position of styrene (14-26)aswell as alkenes bearing polycyclic aromatic hydrocarbons (27,28)and heterocyclic systems 29-31 (31 including SC-XRD), all gave the desired trifluoroacylated adducts. Similarly,t he key precursors (32, 33 and 34)o fm ost Angewandte Chemie Forschungsartikel 22662 www.angewandte.de recognized anti-inflammatory drugs bearing trifluoromethylated pyrazole moieties such as Mavacoxib,C elecoxib,a nd SC-560 [52][53][54][55] were all synthesized using this photoredox protocol in satisfactory yields.Inmost cases,wewere unable to observe trifluoromethylated or difunctionalized alkene adducts.H aving enabled for the trifluoroacetylation of alkenes with as imple reagent, we subsequently investigated the application of our protocol in late-stage functionalization. In recent decades,trifluoroacetyl-containing compounds have proven to be an important class of molecules for the preparation of biorelevant substances,and as such we foresaw that our approach could be of particular value in the context of medicinal chemistry.…”

Section: Resultsmentioning

confidence: 99%

“…Substrates adorned with a substituent flanking the -position of styrene (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26) as well as alkenes bearing polycyclic aromatic hydrocarbons (27,28) and heterocyclic systems 29-31 (31 including SC-XRD), all gave the desired trifluoroacylated adducts. Similarly, the key precursors (32, 33 and 34) of most recognized antiinflammatory drugs bearing trifluoromethylated pyrazole moieties such as Mavacoxib, Celecoxib and SC-560 [50][51][52] were all synthesized using this photoredox protocol in satisfactory yields. In most cases, we were unable to observe trifluoromethylated or difunctionalized alkene adducts.…”

Section: Reaction Scope and Synthetic Applicationmentioning

confidence: 99%

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

et al. 2021

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Trifluoromethyl ketones are not only found in drug like substances, but are also considered as key synthons for the preparation of various fluorinated heterocyclic molecules.Access to such trifluoromethyl ketone derivatives typically requires the incorporation of the trifluoromethyl group, or a surrogate moiety, at the beginning of a multi-step synthetic sequence. However, direct trifluoroacylation of alkenes could potentially provide a highly efficient and straightforward method for the synthesis of -unsaturated trifluoromethyl ketones. Here we report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low-cost and readily available reagent. This light-mediated process is fundamentally different from conventional methodologies and occurs through an trifluoroacyl radical mechanism promoted by a photocatalyst. Beyond simple alkenes, this method allows for chemo-and regioselective functionalization of small-molecule drugs and common pharmacophores. . 90's, Balenkova and co-workers reported the method for the activation of TFAA by in situ generated BF3(gas)/Me2S complex at -60 ºC, allowing direct olefinic trifluoroacetylation ostensibly via an effect of kH/kD= 1.3 per deuterium further hints on the existence of conjugation effects (for extensive discussions, see ESI). However, this step might also directly employ a proton coupled electron transfer as previously described for the corresponding anions. [62][63][64] On basis of these electrochemical characteristics, we propose a slow depopulation of the equilibrium 59/61 through the reductive quenching by the Ir(IV) ground state. The subsequent irreversible deprotonation of the strongly acidic cation 62 with trifluoroacetate or the TFAA-radical anion occurs with the concurrent formation of the reaction product. ConclusionIn summary, we have developed an efficient and practical protocol where the simple reagent TFAA undergoes chemo-and regioselective trifluoroacylation reaction with a broad range of alkenes including complex natural products to access -unsaturated trifluoromethyl ketone derivatives. Detailed mechanistic studies have provided evidence that C-CF3 and C-COCF3 bond formation can be controlled under different reaction conditions. With this remarkable disclosure, we anticipate that this trifluoroacetylation approach will be a valuable tool for the synthetic chemist in drug discovery and development. MethodsGeneral procedure for photocatalytic trifluoroacetylation of alkenes. A 10-mL glass microwave vial was charged with photocatalyst (1 mol%). The contents of the vial were then subject to 3x argon/vacuum cycles. Anhydrous EtOAc was added and the reaction mixture was sparged with argon for 3 min. Finally, the substrate (1.0 equiv) and TFAA (2.0 equiv) were introduced to the reaction mixture via microsyringe.The obtained red solution was stirred at room temperature under blue LED irradiation. After 12 hours, water was added to the reaction mixture and the product was extracted with CH2Cl2 (...

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“…The X-ray crystallographic structure of COX-1 (PDB ID: 3KK6) and COX-2 (PDB ID: 3LN1) was downloaded from the protein data bank website. 24) In this study, COX-1 (PDB ID: 3KK6) and COX-2 (PDB ID: 3LN1) cocrystalized with celecoxib were chosen for molecular docking. The docking images were analyzed by UCSF Chimera.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Salicylic Acid Analogues of Celecoxib as a New Class of Selective Cyclooxygenase-1 Inhibitor

Yoon

Cho

Choi

et al. 2021

Biological & Pharmaceutical Bulletin

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A series of salicylic acid analogues of celecoxib where the phenylsulfonamide moiety in the structure of celecoxib is replaced by salicylic acid moiety was synthesized and tested for in vitro cyclooxygenase (COX)-1 and COX-2 enzyme inhibition. Among the series, 5-substituted-2-hydroxy-benzoic acid analogues (7a-7h) generally showed better inhibitory activities on both enzymes than 4-substituted-2-hydroxy-benzoic acid analogues (12a-12h). In particular, the chloro analogue 7f which had the highest inhibitory effect (IC 50 0.0057 µM) to COX-1 with excellent COX-1 selectivity (SI 768) can be classified as a new potent and selective COX-1 inhibitor. The high inhibitory potency of 7f was rationalized through the docking simulation of this analogue in the active site of COX-1 enzyme.

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Regioselectively controlled synthesis of 3(5)-(trifluoromethyl)pyrazolylbenzenesulfonamides and their effects on a pathological pain model in mice

Cited by 25 publications

References 66 publications

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

Radical Trifluoroacetylation of Alkenes Triggered by a Visible‐Light‐Promoted C–O Bond Fragmentation of Trifluoroacetic Anhydride

Synthesis and Biological Evaluation of Salicylic Acid Analogues of Celecoxib as a New Class of Selective Cyclooxygenase-1 Inhibitor

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