New pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors

Ceruso, Mariangela; Bielawska, Anna; Bielawski, Krzysztof; Fornal, Emilia; Supuran, Claudiu T.

doi:10.1016/j.bmc.2015.04.011

Cited by 41 publications

(34 citation statements)

References 44 publications

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“…This derivative had a K i value of 82.8, >50 000, and 810 nM against hCA XII, hCA II and hCA I, respectively. 293 Carradori et al synthesized amide derivatives of probenecid which has demonstrated effective and selective inhibition against hCA IX/hCA XII. These probenecids did not display inhibition against hCA I and hCA II (K i s > 10 000 nM).…”

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confidence: 99%

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Mishra

Tiwari

Supuran

2020

Medicinal Research Reviews

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188

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Carbonic anhydrases (CAs, EC 4.2.1.1) are widely distributed metalloenzymes in both prokaryotes and eukaryotes. They efficiently catalyze the reversible hydration of carbon dioxide to bicarbonate and H + ions and play a crucial role in regulating many physiological processes. CAs are wellstudied drug target for various disorders such as glaucoma, epilepsy, sleep apnea, and high altitude sickness. In the past decades, a large category of diverse families of CA inhibitors (CAIs) have been developed and many of them showed effective inhibition toward specific isoforms, and effectiveness in pathological conditions in preclinical and clinical settings. The discovery of isoform-selective CAIs in the last decade led to diminished side effects associated with off-target isoforms inhibition. The many new classes of such compounds will be discussed in the review, together with strategies for their development. Pharmacological advances of the newly emerged CAIs in diseases not usually associated with CA inhibition (neuropathic pain, arthritis, cerebral ischemia, and cancer) will also be discussed.

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mentioning

confidence: 99%

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Mishra

Tiwari

Supuran

2020

Medicinal Research Reviews

Self Cite

188

166

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“…Compound 8c , 4‐ethoxy‐ N ‐(2‐hydroxypropyl)‐3‐(3‐methyl‐1‐(p‐tolyl)‐1 H ‐pyrazolo[4,3‐ e ][1,2,4]triazin‐5‐yl)benzenesulfonamide, exhibited the highest activity against Human Carbonic Anhydrase II (hCA II) and Human Carbonic Anhydrase IX (hCA IX) with the inhibition constant (K i ) 13.8 nm, with a tumor associated transmembrane protein (Mojzych et al, ).…”

Section: Synthesis and Anticancer Activity Of Nostocine Derivativesmentioning

confidence: 99%

“…Indeed, 1,3‐dimethyl substituted and 5‐ethoxyphenyl benzene sulfonamide bearing 1,4‐diazepine nucleus were connected at N‐1, C‐3, and C‐5 positions of scaffold pyrazolotriazine moiety (7) , respectively; eventually, the compound had anticancer activity against Abl tyrosine kinase, significantly (Mojzych, Ceruso, et al, ).…”

Section: Sar Of Nostocine Derivatives With Anticancer Activitymentioning

confidence: 99%

Nornostocine congeners as potential anticancer drugs: An overview

Sahoo

Paidesetty

Padhy

2019

Drug Development Research

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The naturally occurring phyco‐constituent nostocine A, bearing the pyrazolotriazine scaffold in its structural frame, belongs to an organic class of pharmacologically curious candidates with a remarkable anticancer activity. This review summarizes the chemistry of numerous synthetic strategies of demethylated nostocine as “nornostocine derivatives,” in which the substitutes are connected to a few functionalities with the pyrazolotriazine moiety at N‐1, C‐3, and C‐5 positions. These strategies may provide a framework to design and develop a novel potent anticancer drug candidate(s) with an augment of structure activity relationship related to anticancer activities.

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“…Interestingly, 1,2,4‐triazine derivatives have been reported for their diverse biological activities such as anticancer , antibacterial , antidiabetic , antifungal , antimalarial , neuroprotective agents , anticonvulsant , and antiviral activities.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

Sahu

Siddiqui

Naim

et al. 2017

Archiv der Pharmazie

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A series of new pyrimidine-triazine hybrids (4a-t) was designed and synthesized, from which potent anticonvulsant agents were identified. Most of the compounds exhibited promising anticonvulsant activity against the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) tests, along with minimal motor impairment with higher safety compared to the standard drugs, phenytoin and carbamazepine. In the series, 5-(4-(4-fluorophenyl)-6-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4o) and 5-(6-(4-hydroxy-3-methoxyphenyl)-4-(4-hydroxyphenyl)-2-thioxo-5,6-dihydropyrimidin-1(2H)-yl)-1,2-dihydro-1,2,4-triazin-3(6H)-one (4s) emerged as most potent anticonvulsant agents with median doses of 22.54 and 29.40 mg/kg (MES ED ), 285.02 and 293.42 mg/kg (scPTZ ED ), and 389.11 and 412.16 mg/kg (TD ), respectively. Docking studies were also performed for all synthesized compounds to get insight into the binding pattern toward the GABA receptor as a possible mechanism of their anticonvulsant action, and in silico ADME studies were carried out to predict the safety and stability of the molecules. The increased GABA level in the experimental animals in the neurochemical estimation assay confirmed their GABAergic modulating activity. The most potent compounds were also evaluated for their neurotoxic and hepatotoxic effects. Fortunately, they did not show any sign of neurotoxicity or hepatotoxicity, suggesting that they have a broad spectrum of anticonvulsant activity with a large safety margin. Together, this research suggested that 4o and 4s may serve as leads in the discovery and development of new anticonvulsant drugs.

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New pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors

Cited by 41 publications

References 44 publications

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Nornostocine congeners as potential anticancer drugs: An overview

Design, Synthesis, and Docking Study of Pyrimidine–Triazine Hybrids for GABA Estimation in Animal Epilepsy Models

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