Potential Antileishmanial Activity of 4-N-Acylhydrazone Pyrazolo[3,4-d]pyridazin-7-ones: Synthesis, in vitro Biological Evaluations and Computational Studies

Jacomini, Andrey P.; Silva, Michael J. V. da; Poletto, Julia; Ribeiro, Gessica M.; Yokoyama, Jéssica T.C.; Bidóia, Danielle Lazarin; Paula, Fávero Reisdorfer; Nakamura, Celso V.; Sarragiotto, María Helena; Rosa, Fernanda A.

doi:10.21577/0103-5053.20180134

Cited by 6 publications

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“…Our strategy offers a method for synthesizing pyrazolo-pyridazinone systems that might have potential antileishmanial activity. 18 Furthermore, we successfully obtained a single crystal suitable for X-ray crystallographic analysis of derivative 7a (see Figure S1 and Table S3 for full details, Supporting Information). The X-ray structure of 7a allowed unambiguously to confirm the structure of regioisomer 4.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…At last, product 4a was easily converted to corresponding hydrazide 6a and N -acyl-hydrazone derivative 7a , in good yields (Scheme ). Our strategy offers a method for synthesizing pyrazolo-pyridazinone systems that might have potential antileishmanial activity . Furthermore, we successfully obtained a single crystal suitable for X-ray crystallographic analysis of derivative 7a (see Figure S1 and Table S3 for full details, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

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Controlled Pyrazole-Hydrazone Annulation: Regiodivergent Synthesis of 1H- and 2H-Pyrazolo[3,4-d]pyridazinones

et al. 2023

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An efficient and controlled site-selective annulation of 3,5-diethoxycarbonyl 4-hydrazonyl pyrazoles is described. The relative proportion of the products is affected by hydrazone intermediate configuration, reaction temperature, and Lewis acid employed. At a temperature of 110–120 °C, the reaction preferentially afforded 1H-pyrazolo[3,4-d]pyridazin-7(6H)-ones, whereas using Yb(OTf)3 in MeCN reflux, 2H-pyrazolo[3,4-d]pyridazin-7(6H)-ones were favored. Computational investigations were performed to clarify the mechanism and the origin of the regiodivergence.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Controlled Pyrazole-Hydrazone Annulation: Regiodivergent Synthesis of 1H- and 2H-Pyrazolo[3,4-d]pyridazinones

et al. 2023

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“…Using a similar approach, but aiming for the synthesis of novel NAH derivatives, pyrazole 19 (in which R = CO 2 Et) was converted into the pyridazinones 66 (hydrazine hydrate, AcOH, reflux for 12 h) at yields of 69–87 %, which were later reacted with hydrazine hydrate in refluxing EtOH/MeCN for 24 h to yield hydrazides 67 at yields of 92–95 %. [ 43,77 ] The NAH derivatives 68 were finally achieved by reaction with benzaldehydes, to yield the products at 94–98 % (Scheme 24).…”

Section: Synthesis Of Pyridazinonesmentioning

confidence: 99%

The Wonderful World of β‐Enamino Diketones Chemistry

et al. 2020

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The simple preparation and functionalization of oxa/aza heterocycles requires new and efficient starting materials to be discovered so that regioselective methodologies with a wide range of applications in organic synthesis can be developed. With this in mind, β‐enamino diketones have emerged as a suitable building block for preparing the most diverse (poly)heterocyclic systems, through cyclocondensation or cycloaddition reactions. This review compiles all the reactions that have been conducted using these starting materials, ever since they were first disclosed in 1980.

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“…Thus, our research group has focused on the development of methodologies for the synthesis of these hybrids and evaluated their antileishmanial effects. We reported the synthesis and in vitro antileishmanial activity of a series of 1,4,6‐trisubstituted pyrazolo[3,4‐ d ]pyridazin‐7‐one‐ N ‐acylhydrazone hybrids forward promastigote and amastigote forms of Leishmania amazonensis (Jacomini et al, 2016; Jacomini et al, 2018). Hybrids I , II , and III exhibited good activity values against both forms of L. amazonensis , with excellent values for compound II (IC 50(pro) = 3.63 μM, IC 50(ama) = 2.32 μM) and remarkable selectivity index (SI > 52.71 and 82.48) (Figure 1a).…”

Section: Introductionmentioning

confidence: 99%

Antiparasitic activities of novel pyrimidine N‐acylhydrazone hybrids

Poletto

Silva

Jacomini

et al. 2020

Drug Development Research

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In this article, a series of 29 new pyrimidine N‐acylhydrazone hybrids were synthesized and evaluated in vitro against Leishmania amazonensis and Trypanosoma cruzi protozoa that cause the neglected diseases cutaneous leishmaniasis and Chagas disease, respectively. Eight of the target compounds showed significant antiprotozoal activities with IC50 values in 4.3–33.6 μM range. The more active compound 4f exhibited selectivity index greater than 15 and drug‐like properties based on Lipinski's rule.

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Potential Antileishmanial Activity of 4-N-Acylhydrazone Pyrazolo[3,4-d]pyridazin-7-ones: Synthesis, in vitro Biological Evaluations and Computational Studies

Cited by 6 publications

References 0 publications

Controlled Pyrazole-Hydrazone Annulation: Regiodivergent Synthesis of 1H- and 2H-Pyrazolo[3,4-d]pyridazinones

Controlled Pyrazole-Hydrazone Annulation: Regiodivergent Synthesis of 1H- and 2H-Pyrazolo[3,4-d]pyridazinones

The Wonderful World of β‐Enamino Diketones Chemistry

Antiparasitic activities of novel pyrimidine N‐acylhydrazone hybrids

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