vestichИзвестия Национальной академии наук Беларуси. Серия химических наукProceedings of the National Academy of Sciences of Belarus, Chemical Series1561-83312524-2342The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1561-8331-2020-56-1-81-87vestich-569Research ArticleБИООРГАНИЧЕСКАЯ ХИМИЯBIOORGANIC CHEMISTRYПотенциальные ингибиторы ароматазы и антиэстрогенные агенты на основе производных стильбена и стильбазоловPotential aromatase inhibitors and antiestrogen agents based on stilbene and stilbazole derivativesАдамчикС. В.AdamchykS. V.

Адамчик Сергей В. – научный сотрудник

ул. акад. Купревича, 5/2, 220141, Минск

Siarhei V. Adamchyk – Researcher

5/2, Cuprevich Str., 220141, Minsk

sergey.adamchik@gmail.comМихальчукА. Л.Michal’chukA. L.

Михальчук Александр Леонидович – кандидат химических наук, ведущий научный сотрудник

ул. акад. Купревича, 5/2, 220141, Минск

Alexander L. Michal’chuk – Ph. D. (Chemistry), Leading Researcher

5/2, Cuprevich Str., 220141, Minsk

lipmal@iboch.byИнститут биоорганической химии Национальной академии наук БеларусиInstitute of Bioorganic Chemistry of the National Academy of Sciences of Belarus2020190320205618187Copyright © Адамчик С.В., Михальчук А.Л., 20202020Адамчик С.В., Михальчук А.Л.Adamchyk S.V., Michal’chuk A.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestichem.belnauka.by/jour/article/view/569

Антиэстрогенная терапия занимает важное место в предупреждении, лечении и профилактике рецидивов гормонозависимого рака молочной железы. Одним из способов снижения продукции женских половых гормонов в постменопаузе является применение ингибиторов ароматазы, фермента семейства цитохромов, превращающего андрогены в эстрогены. С целью поиска новых ингибиторов и исследования взаимосвязи структура функция получен ряд производных E- и Z-стильбенов и стильбазолов: 4-(2-(пиридин-4-ил)-1-(1H-1,2,4-триазол-1-ил)винил) бензонитрила, 4-(2-(пиридин-3-ил)-1-(1H-1,2,4-триазол-1-ил)винил)бензонитрила, 4-(2-(4-фторфенил)-1-(1H-1,2,4триазол-1-ил)винил)бензонитрила, 4-(2-(4-хлорфенил)-1-(1H-1,2,4-триазол-1-ил)винил)бензонитрила, 4-(2-(4-бромфенил)1-(1H-1,2,4-триазол-1-ил)винил)бензонитрила и 4-(2-(3,4-диметоксифенил)-1-(1Р-1,2,4-триазол-1-ил)винил)бензонитрила. Соединения получены конденсацией 4-((1H-1,2,4-триазол-1-ил)метил)бензонитрила с соответствующим альдегидом с последующей дегидратацией образующегося спирта. Обнаружено, что в ходе дегидратации образуются преимущественно Z-изомеры стильбенов и стильбазолов. Соответствующие им E-изомеры получены фотоизомеризацией Z-олефинов.

Abstract. Widely used forms of endocrine therapy for women with hormone-dependent breast cancer include blocking the biosynthesis of estrogens through using inhibitors of cytochrome P450 19A1 (aromatase). A series of new stilbene and stilbazole based aromatase inhibitors on are prepared. Z-isomers of 4-(2-(pyridin-4-yl)-1-(1H-1,2,4-triazol-1-yl)vinyl) benzonitrile, 4-(2-(pyridin-3-yl)-1-(1H-1,2,4-triazol-1-yl)vinyl)benzonitrile, 4-(2-(4-fluorophenyl)-1-(1H-1,2,4-triazol1-yl)vinyl)benzonitrile, 4-(2-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)vinyl)benzonitrile, 4-(2-(4-bromophenyl)-1-(1H-1,2,4triazol-1-yl)vinyl)benzonitrile, 4-(2-(3,4-dimethoxyphenyl)-1-(1H-1,2,4-triazol-1-yl)vinyl)benzonitrile were prepared by condensation of 4-((1H-1,2,4-triazol-1-yl)methyl)benzonitrile and corresponding aldehyde in presence of strong base followed by dehydration of obtained alcohols. Isomerization to corresponded E-isomers was carried out in the presence of UV light.

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The authors declare that there are no conflicts of interest present.