The competitive N1-, N2-, O- and C-methylation of 3-trifluoromethyl-1H-pyrazol-5-ol for synthesis of analgesic compounds

Burgart, Yanina V.; Agafonova, N. A.; Shchegolkov, Evgeny V.; Borisevich, Sophia S.; Хурсан, С. Л.; Маслова, Вера В.; Триандафилова, Галина А.; Solodnikov, S. Yu.; Красных, О. П.; Салоутин, В. И.

doi:10.1016/j.jfluchem.2018.11.009

Cited by 8 publications

(7 citation statements)

References 31 publications

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“…4, Fig. 5 to be used as complementary data for crystal of ( Z )-1-[4-(trifluoromethyl)benzylidene]thiosemicarbazide [1] with CCDC:1507979 and were supported by other previous publications [2,3]. Both Fig.…”

Section: Datasupporting

confidence: 60%

Correlation data of (Z)-1-[4-(trifluoromethyl)benzylidene]thiosemicarbazide via spectroscopic methods and Density Functional Theory studies

et al. 2019

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New compound, namely (Z)-1-[4-(trifluoromethyl)benzylidene]thiosemicarbazide was successfully synthesized using thiosemicarbazide with 4-(trifluoromethyl)-benzaldehyde in ethanol solution. The data presented in this articles is related to our research articles entitled “Crystal Structure of (Z)-1-[4-(Trifluoromethyl)benzylidene]thiosemicarbazide” (Osman et al., 2017) [1]. This work shows the continue data from experimental spectroscopic measurement which are Fourier Transform Infrared (FTIR) and 13C Nuclear Magnetic Resonance (13C NMR). Assessment on the correlation with theoretical computational data was also carried out through GaussView 5.0.9 and Gaussian09 software. Molecular Electrostatic Potential (MEP) and Highest Occupied Molecular Orbital–Lowest Unoccupied Molecular Orbital (HOMO-LUMO) were also illustrated.

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Section: Datasupporting

confidence: 60%

Correlation data of (Z)-1-[4-(trifluoromethyl)benzylidene]thiosemicarbazide via spectroscopic methods and Density Functional Theory studies

et al. 2019

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“…Later the authors performed analogous studies with fluorinated pyrazolone 549 (Scheme 94). 219 With an excess of Me 2 SO 4 , dimethyl-substituted compound 550 was obtained. With 1 equiv of Me 2 SO 4 in toluene, formation of N-alkylated product 551 was observed.…”

Section: Derivatizations Of Fluorinated Pyrazolesmentioning

confidence: 99%

Fluorinated Pyrazoles: From Synthesis to Applications

2020

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Fluorinated pyrazoles play an important role in medicinal chemistry, drug discovery, agrochemistry, coordination chemistry, and organometallic chemistry. Since the early 1990s, their popularity has grown exponentially. Moreover, more than 50% of all contributions on the topic have been published in the last 5 years. In this review, analysis of novel synthetic approaches to fluorinated pyrazoles that appeared in recent years is performed. A particular emphasis is devoted to a detailed consideration of reaction mechanisms. In addition, the reasons that have led to the ever-increasing popularity of fluorinated pyrazoles in various areas of science are discussed. At the end of the review, several potentially interesting but yet mostly unknown classes of fluorinated pyrazoles are outlined.

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“…We have found earlier the similar alternative course of reactions in the study of polyfluoroalkylpyrazoles 1 a,b methylation. [26] In this work, N-methylation was established to occur predominantly under conditions without a base, while the use of a base leads to selective Omethylation. Diagnostic features were also found that allowed us to attribute the resulting products to the O-or N-isomer series.…”

Section: Resultsmentioning

confidence: 99%

“…[25] We are also actively carrying out research on the development of analgesics based on fluorine-containing pyrazoles. [26][27][28][29][30][31][32] Recently, we have synthesized polyfluoroalkylcontaining MeN-and MeO-derivatives of pyrazol-5-ols as analogues of antipyrine and celecoxib, [33] which revealed the pronounced analgesic activity in the hot plate test. Among the obtained derivatives, 5-methoxy-3-(trifluoromethyl)-1phenylpyrazole was distinguished by a combination of high analgesic activity in the in vivo hot plate test with low acute toxicity, which is a very important point for the development of new analgesics.…”

Section: Introductionmentioning

confidence: 99%

“…We are also actively carrying out research on the development of analgesics based on fluorine‐containing pyrazoles [26–32] . Recently, we have synthesized polyfluoroalkyl‐containing MeN‐ and MeO‐derivatives of pyrazol‐5‐ols as analogues of antipyrine and celecoxib, [33] which revealed the pronounced analgesic activity in the hot plate test.…”

Section: Introductionmentioning

confidence: 99%

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5‐Alkoxy‐1‐aryl‐3‐polyfluoroalkylpyrazoles with Antinociceptive Activity: Partial Agonists of TRPV1 Ion Channels

et al. 2023

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Chemoselective O‐alkylation of 1‐aryl‐3‐polyfluoroalkylpyrazol‐5‐oles under basic conditions resulted in a series of 5‐alkoxypyrazoles (26 derivatives). They showed an acceptable ADME profile (in silico) and can be considered as drug‐like. In experiments in vivo (CD‐1 mice), it was found that the obtained compounds do not have toxic properties at a dose of more than 150 mg/kg (for most compounds at a dose of >300 mg/kg, and for lead compounds – >600 mg/kg). 22 Compounds from this series demonstrated from moderate to high analgesic effects (28–104 % at 1 h and 37–109 % at 2 h after administration) in vivo in the hot plate test (SD rats, 15 mg/kg, intraperitoneal (ip)). The lead compound was 4‐([1‐phenyl‐3‐(trifluoromethyl)pyrazol‐5‐yl]oxy)butan‐1‐ol, which not only increased the latent period in the hot plate test by 103 % at both measurement points but also showed a pronounced analgesic effect under conditions of capsaicin‐induced nociception (CD‐1 mice, 15 mg/kg, ip). According to molecular modeling, all synthesized compounds can interact with the TRPV1 ion channel. This biological target was confirmed in in vitro experiments on Chinese hamster ovary cells expressing rTRPV1. 5‐Alkoxypyrazoles were partial agonists of the TRPV1 ion channel in various degree, and the most active was the same pyrazole as in in vivo tests.

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The competitive N1-, N2-, O- and C-methylation of 3-trifluoromethyl-1H-pyrazol-5-ol for synthesis of analgesic compounds

Cited by 8 publications

References 31 publications

Correlation data of (Z)-1-[4-(trifluoromethyl)benzylidene]thiosemicarbazide via spectroscopic methods and Density Functional Theory studies

Correlation data of (Z)-1-[4-(trifluoromethyl)benzylidene]thiosemicarbazide via spectroscopic methods and Density Functional Theory studies

Fluorinated Pyrazoles: From Synthesis to Applications

5‐Alkoxy‐1‐aryl‐3‐polyfluoroalkylpyrazoles with Antinociceptive Activity: Partial Agonists of TRPV1 Ion Channels

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