Multiple biological active 4-aminopyrazoles containing trifluoromethyl and their 4-nitroso-precursors: Synthesis and evaluation

Burgart, Yanina V.; Agafonova, N. A.; Shchegolkov, Evgeny V.; Красных, О. П.; Kushch, Svetlana O.; Евстигнеева, Н. П.; Герасимова, Н. А.; Маслова, Вера В.; Триандафилова, Галина А.; Solodnikov, S. Yu.; Улитко, М. В.; Махаева, Галина Ф.; Рудакова, Е. В.; Borisevich, Sophia S.; Зильберберг, Н. В.; Кунгуров, Н. В.; Салоутин, В. И.; Чупахин, О. Н.

doi:10.1016/j.ejmech.2020.112768

Cited by 22 publications

(12 citation statements)

References 96 publications

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“…From the current state of facts, it appears that research activity toward the synthesis and properties of fluorinated pyrazoles will continue to grow. In the coming years, we are about to see novel intriguing applications of fluorinated pyrazoles in various areas of chemistry and the development of more efficient synthetic methods for their preparation. − …”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

Fluorinated Pyrazoles: From Synthesis to Applications

2020

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“…Further, the analgesic activity of pyrazoles 3 was studied in the “hot plate” test on SD rats at the dose of 15 mg/kg; metamizole and diclofenac sodium were used as reference drugs (Table 2). It has been previously shown [29] that aminopyrazoles 2 a , b (i. e. hydrochlorides) have analgesic activity at the level of the reference drugs: the hot plate latency period prolongation (LPP) after 1 h was 91.8 and 100.7 %, respectively. The corresponding base form – aminopyrazole 1a – turned out to be less toxic than compound 2a , however, its activity decreased markedly: LPP for 1st hour of the experiment was 56.7 % and for 2nd hour LPP 66.7 % (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…The initial compounds 1 a , b , 2 a , b [29] and 1 c [30] were synthesized by referring previously published methods.…”

Section: Methodsmentioning

confidence: 99%

Modifications of 4‐Amino‐substituted 5‐Phenyl‐3‐(trifluoromethyl)pyrazoles for the Development of New Analgesics

Shchegolkov,

Perminova,

Malkova

et al. 2023

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To develop the new analgesics, different approaches to the modification of 4‐amino‐5‐phenyl‐3‐(trifluoromethyl)pyrazoles were proposed. A series of 4‐(het)arylimino‐3‐(trifluoromethyl)‐5‐phenylpyrazoles, existing as the E‐isomer, was synthesized by condensation of the 4‐aminopyrazoles with various aldehydes. Methylation of the initial substrates occurred at the NH2 group, while alkylation with bromobutyl was successfully carried out only for NH‐pyrazole to yield 3‐ and 5‐CF3‐isomeric N‐butyl‐substituted pyrazoles. The addition of phenylisothiocyanate to 4‐aminopyrazoles allowed us to introduce a thiourea fragment into their structure. According to computer calculations, all derivatives of aminopyrazoles have an acceptable ADME profile. Using the “hot plate” test in vivo, the analgesic activity of a number of the synthesized compounds was evaluated. Introducing the phenylmethanimine fragment allows us to obtain 1‐phenyl‐N‐(5‐phenyl‐3‐(trifluoromethyl)pyrazol‐4‐yl)methan‐imine as the lead compound with the analgesic activity in 1.4–2.2 times more than effect of the initial 4‐aminopyrazole, diclofenac and metamizole. In addition, the lead compound had low acute toxicity.

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“…For example, 4‐nitrosopyrazoles are characterized by the formation of a resonance‐stabilized anion [7d] . Nitroso compounds have unique reactivities and can be reduced to amino compounds, [7f,8] oxidized to nitro compounds, [9] or enter into the nitroso Diels‐Alder (NDA) reaction [10] . A large number of works have been devoted to the condensation reactions of nitroso compounds with nucleophilic reagents [11]…”

Section: Introductionmentioning

confidence: 99%

First N‐Functionalization of 4‐Nitroso‐1H‐Pyrazoles Using Monofunctional and Bifunctional Alkylating Agents

et al. 2023

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The direct N‐alkylation reactions of ambident 3,5‐substituted 4‐nitroso‐1H‐pyrazoles are described for the first time. An efficient method of the 4‐nitroso‐1H‐pyrazoles and their sodium alkyl‐, allyl‐ salts regioselective N‐alkylation by benzyl halides, halocarboxylic acids esters, and related bifunctional alkylating agents is established with the use of superbasic conditions or reflux in acetone. A series of new N‐functionalized nitrosopyrazoles and bis(4‐nitrosopyrazole) compounds is successfully obtained with a yield of up to 85 %. Using quantum‐chemical calculations, it is shown that in terms of kinetics and thermodynamics, the N‐alkylation of the considered pyrazoles is a more advantageous process than O‐alkylation.

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Multiple biological active 4-aminopyrazoles containing trifluoromethyl and their 4-nitroso-precursors: Synthesis and evaluation

Cited by 22 publications

References 96 publications

Fluorinated Pyrazoles: From Synthesis to Applications

Fluorinated Pyrazoles: From Synthesis to Applications

Modifications of 4‐Amino‐substituted 5‐Phenyl‐3‐(trifluoromethyl)pyrazoles for the Development of New Analgesics

First N‐Functionalization of 4‐Nitroso‐1H‐Pyrazoles Using Monofunctional and Bifunctional Alkylating Agents

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