586333-28-0Relevant academic research and scientific papers
Mild and Regioselective Synthesis of 3-CF3-Pyrazoles by the AgOTf-Catalysed Reaction of CF3-Ynones with Hydrazines
Topchiy, Maxim A.,Zharkova, Daria A.,Asachenko, Andrey F.,Muzalevskiy, Vasiliy M.,Chertkov, Vyacheslav A.,Nenajdenko, Valentine G.,Nechaev, Mikhail S.
supporting information, p. 3750 - 3755 (2018/07/31)
Gold- and silver-catalysed reactions of trifluoromethylated ynones with aryl (alkyl) hydrazines were investigated. The use of (THD-Dipp)AuOTf and AgOTf resulted in quick heterocyclization reactions to selectively give 3-CF3-pyrazoles. AgOTf was found to be the catalyst of choice, and various 3-CF3-pyrazoles were formed in up to 99 % isolated yield with high regioselectivity. The reaction has a broad scope: 3-CF3-pyrazoles with alkyl and aryl substituents as well as different functional groups can be prepared by this approach. The known pyrazole drugs Celebrex and SC-560 were efficiently prepared to demonstrate the utility of the method. Mechanistic investigations revealed that the reaction involves the formation of a hemiaminal as a key intermediate.
Selective, Metal-Free Approach to 3- or 5-CF3-Pyrazoles: Solvent Switchable Reaction of CF3-Ynones with Hydrazines
Muzalevskiy, Vasiliy M.,Rulev, Alexander Yu.,Romanov, Alexey R.,Kondrashov, Evgeniy V.,Ushakov, Igor A.,Chertkov, Vyacheslav A.,Nenajdenko, Valentine G.
, p. 7200 - 7214 (2017/07/26)
A detailed study of the reaction of trifluoroacetylated acetylenes and aryl (alkyl) hydrazines was performed, aimed to the regioselective synthesis of 3- or 5-trifluoromethylated pyrazoles. It was found that the regioselectivity of reaction depends dramatically on the solvent nature. Highly polar protic solvents (hexafluoroisopropanol) favor the formation of 3-trifluoromethylpyrazoles. In contrast, when the reaction was performed in polar aprotic solvents (DMSO), the formation of their 5-CF3-substituted isomers was preferentially observed. Alternatively, the regioselective assembly of 3-CF3-substituted pyrazoles can be performed via two-step one-pot procedure. The reaction of trifluoromethylated ynones with aryl (alkyl) hydrazines in the presence of acidic catalysts leads to formation of the corresponding hydrazones. The latter can be smoothly transformed into 3-CF3-pyrazoles by treatment with a base. This solvent-switchable procedure was used for the preparation of such important drugs as Celebrex and SC-560 as well as their isomers in gram scale. The possible reaction mechanism is discussed.
Synthesis of 3-trifluoromethylpyrazoles via trifluoromethylation/ cyclization of α,β-alkynic hydrazones using a hypervalent iodine reagent
Ji, Guojing,Wang, Xi,Zhang, Songnan,Xu, Yan,Ye, Yuxuan,Li, Ming,Zhang, Yan,Wang, Jianbo
supporting information, p. 4361 - 4363 (2014/04/17)
A mild and efficient method for the synthesis of 3-trifluoromethylpyrazoles has been established via trifluoromethylation/cyclization of α,β-alkynic hydrazones using a hypervalent iodine reagent under transition-metal-free conditions.
Synthesis, biological evaluation and molecular modeling study of pyrazole and pyrazoline derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Part 2
El-Sayed, Magda A.-A.,Abdel-Aziz, Naglaa I.,Abdel-Aziz, Alaa A.-M.,El-Azab, Adel S.,Eltahir, Kamal E.H.
scheme or table, p. 3306 - 3316 (2012/07/14)
New pyrazole and pyrazoline derivatives have been synthesized and their ability to inhibit ovine COX-1/COX-2 isozymes was evaluated using in vitro cyclooxygenase (COX) inhibition assay. Among the tested compounds, N-((5-(4-chlorophenyl)-1-phenyl-3-(triflu
Synergic effects of ionic liquid and microwave irradiation in promoting trifluoromethylpyrazole synthesis
Buriol, Lilian,Frizzo, Clarissa P.,Prola, Lizie D. T.,Moreira, Dayse N.,Marzari, Mara R. B.,Scapin, Elisandra,Zanatta, Nilo,Bonacorso, Helio G.,Martins, Marcos A. P.
experimental part, p. 1130 - 1135 (2012/06/18)
The synthesis of 5-trifluoromethyl-1-phenyl-1H-pyrazoles from the reactions of 4-alkoxy-1,1,1-trifluoro-3-alken-2-ones [CF3C(O)CH=C(R 1)OR, where R = Me, Et; R1= H, Me, Bu, i-Bu, Ph, 4-MeC6H4, 4-FCsu
Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX-2 inhibitors: Molecular docking study
El-Sayed, Magda A.-A.,Abdel-Aziz, Naglaa I.,Abdel-Aziz, Alaa A.-M.,El-Azab, Adel S.,Asiri, Yousif A.,Eltahir, Kamal E.H.
, p. 3416 - 3424 (2011/07/08)
New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesized from 1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione 1. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw oedema model. Moreover, they were tested for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay. Some of the new compounds (2f, 6a and 6d) showed a reasonable in vitro COX-2 inhibitory activity, with IC50 value of 0.45 μM and selectivity index of 111.1. A virtual screening was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. Docking study of the synthesized compounds 2f, 6a and 6d into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.
Improved regioselectivity in pyrazole formation through the use of fluorinated alcohols as solvents: Synthesis and biological activity of fluorinated tebufenpyrad analogs
Fustero, Santos,Roman, Raquel,Sanz-Cervera, Juan F.,Simon-Fuentes, Antonio,Cunat, Ana C.,Villanova, Salvador,Murguia, Marcelo
, p. 3523 - 3529 (2008/09/20)
(Chemical Equation Presented) The preparation of N-methylpyrazoles is usually accomplished through reaction of a suitable 1,3-diketone with methylhydrazine in ethanol as the solvent. This strategy, however, leads to the formation of regioisomeric mixtures of N-methylpyrazoles, which sometimes are difficult to separate. We have determined that the use of fluorinated alcohols such as 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as solvents dramatically increases the regioselectivity in the pyrazole formation, and we have used this modification in a straightforward synthesis of fluorinated analogs of Tebufenpyrad with acaricide activity.
The reaction of aryl and heteroarylhydrazines with aryl-trifluoromethyl β-diketones
Singh, Shiv P.,Kumar, Vinod,Aggarwal, Ranjana,Elguero, Jose
, p. 1003 - 1014 (2007/10/03)
We report the results obtained when five aromatic or heteroaromatic hydrazines react with six β-diketones bearing trifluoromethyl and aryl substituents. Forty-two compounds have been isolated corresponding to two isomeric trifluoromethyl pyrazoles and the
Design and synthesis of novel celecoxib analogues as selective cyclooxygenase-2 (COX-2) inhibitors: Replacement of the sulfonamide pharmacophore by a sulfonylazide bioisostere
Uddin, Md. Jashim,Rao, P.N. Praveen,Knaus, Edward E.
, p. 5273 - 5280 (2007/10/03)
A group of celecoxib analogues in which the para-SO2NH 2 substituent on the N1-phenyl ring was replaced by a para-sulfonylazido (SO2N3) 4, or a meta-SO 2N3 8, substituent were designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 inhibition studies showed that 4-[5-(4-methylphenyl)-3-trifluoromethyl-1H- pyrazol-1-yl]benzenesulfonyl azide (4) with a para-SO2N3 substituent was a selective COX-1 inhibitor. In contrast, 3-[5-(4-methylphenyl)- 3-trifluoromethylpyrazol-1-yl]benzenesulfonyl azide (8a) having a meta-SO 2N3 substituent (COX-1 IC50 >100 μM; COX-2 IC50=5.16 μM; COX-2 selectivity index >19.3) is a selective COX-2 inhibitor. A molecular modeling (docking) study showed that the SO2N3 group of 8a inserts deep inside the secondary pocket of the COX-2 binding site. The SO2N3 moiety of 8a can undergo a dual H-bonding interaction via one of its SO2 oxygen-atoms, and an electrostatic (ion-ion) interaction via the terminal azido (N3) nitrogen-atom, to the guanidino NH2 of Arg 513 in the secondary pocket of COX-2. These observations indicate that an appropriately positioned SO2N3 moiety is a novel alternative bioisostere to the traditional SO2NH2 and SO2Me pharmacophores present in selective COX-2 inhibitors, that are only capable of H-bonding interactions with the COX-2 isozyme, for use in drug design.
