Chemoenzymatic method of 1,2,4-triazole nucleoside synthesis: Possibilities and limitations

Konstantinova, Irina D.; Chudinov, M. V.; Fateev, Ilja V.; Matveev, A. V.; Zhurilo, Nikolay; Швец, В. И.; Мирошников, А. И.

doi:10.1134/s1068162013010056

Cited by 17 publications

(11 citation statements)

References 18 publications

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“…It was previously reported that 1,2,4-triazolecarboxylic acid esters are not PNP substrate [20]. Therefore, only 1,2,4triazole-3-carboxamide 8 (TCA) could be used as a free heterocyclic base in Ribavirin synthesis.…”

Section: Resultsmentioning

confidence: 99%

An Efficient Chemoenzymatic Process for Preparation of Ribavirin

Сахаров

Baykov

Konstantinova

et al. 2015

International Journal of Chemical Engineering

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Ribavirin is an important antiviral drug, which is used for treatment of many diseases. The pilot-scale chemoenzymatic process for synthesis of the active pharmaceutical ingredient Ribavirin was developed with 32% overall yield and more than 99.5% purity. The described method includes the chemical synthesis of 1,2,4-triazole-3-carboxamide, which is a key intermediate and enzyme-catalyzed transglycosylation reaction for preparation of the desired product. 1,2,4-Triazole-3-carboxamide was synthesized from 5-amino-1,2,4-triazole-3-carboxylic acid by classical Chipen-Grinshtein method. Isolated fromE. сoliBL21(DE3)/pERPUPHHO1 strain the purine nucleoside phosphorylase was used as a biocatalytical system. All steps of this process were optimized and scaled.

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Section: Resultsmentioning

confidence: 99%

An Efficient Chemoenzymatic Process for Preparation of Ribavirin

Сахаров

Baykov

Konstantinova

et al. 2015

International Journal of Chemical Engineering

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“…Однако возможны и альтернативные пути фосфорилирования, не связанные с hADK, и другие типы фармакологической активности. В ходе исследования субстратной специфичности генно-инженерной PNP E. сoli [97,98] был получен ряд аналогов рибавирина, N-алкилированных по амидной группе. Как выяснилось, даже объемные заместители в карбоксамидном фрагменте не препятствуют реакции трансгликозилирования, катализируемой PNP (рис.…”

Section: изостерические аналоги по карбоксамидной группеunclassified

“…Выяснилось, что противовирусную активность проявляют не только нуклеозиды или ациклические нуклеозидные аналоги, но и их защищенные производные, и сами гетероциклические основания, у которых активность оказалась максимальна. Предположить в этом случае механизм, включающий синтез нуклеозида из основания с участием PNP, невозможно, так как столь объемный заместитель в 5-ом положении ограничивает субстратную специфичность фермента [97,105]. Остается полагать, что за противовирусную активность отвечает само гетероциклическое основание, а гликозидный фрагмент несет скорее транспортную функцию.…”

Section: аналоги рибавирина замещенные по 5-му положению гетероциклаunclassified

Ribavirin and its analogs: Сan you teach an old dog new tricks?

Chudinov

2019

Fine Chem. Tech.

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The review article focuses on the current state of synthetic and biological studies of ribavirin analogs. Ribavirin is a broad-spectrum nucleoside antiviral drug with a 50-year long history of research and application, but its mechanism of action still remains unclear. This article examines contemporary views on the antiviral and antitumor effects of ribavirin and its analogs and describes the contradictions and gaps that exist in our knowledge. In recent years, new nucleoside analogs of ribavirin have been synthesized. These ribavirin derivatives modified at the heterocyclic base, have the potential to become the antiviral and antitumor agents of the new generation. Thus, this paper presents a systematic review of antiviral activities, antitumor activities and structure–activity relationship (SAR) correlations of 39 ribavirin analogs created in the past 15 years. Biological targets and possible mechanisms of action of these new compounds are also discussed, as well as the prospects and possible directions for further research.

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“…Once absorbed into the bloodstream, viramidine is transformed to ribavirin in the liver and doesn't accumulate in erythrocytes, thus lowering the risks of adverse effects associated with anemia. [47] The research and production of all 1,2,4-triazole compounds as antiviral products have been extensively reviewed in the literature published in the last decade via searching in the SciFinder database. The review article consists of three main sections, based on the ligand chemical structure of the 1,2,4triazole nucleus.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in 1,2,4‐Triazole Scaffolds as Antiviral Agents

El‐Sebaey

2020

ChemistrySelect

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In recent years, severe viral infections have emerged, and antiviral chemotherapeutic agents are not adequately effective in curing these infections, leading to serious human diseases and loss of life. Consequently, a novel antiviral is urgently needed, which undoubtedly essential for the therapy of various fatal and debilitating viral infections. 1,2,4-Triazole derivatives occupy a pivotal position in modern medicinal chemistry and have been incorporated in numerous clinical drugs, including antiviral drugs. To my best knowledge, there are few review articles exclusively handling 1,2,4-triazole scaffold with the antiviral potential. This review aims to figure out recent perspectives and advances of 1,2,4-triazole nucleus roles in various kinds of antiviral agents over the past decade, with some examples of rational design and some structure-activity relationships. This review will hopefully provide perception into especially powerful compounds as lead structures and help in the rational design and development of novel 1,2,4-triazolebased compounds with strong anti-virus efficacy.

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Chemoenzymatic method of 1,2,4-triazole nucleoside synthesis: Possibilities and limitations

Cited by 17 publications

References 18 publications

An Efficient Chemoenzymatic Process for Preparation of Ribavirin

An Efficient Chemoenzymatic Process for Preparation of Ribavirin

Ribavirin and its analogs: Сan you teach an old dog new tricks?

Recent Advances in 1,2,4‐Triazole Scaffolds as Antiviral Agents

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