Synthesis and molecular modeling of thiethane-containing 3-methoxy-4-oxyphenylmethylidenhydrasides 2-[3-methylxanthinyl-8-sulphanil]acetic acids as promising phosphodiesterase 4 inhibitors
- Авторлар: Urazbaev M.A.1, Sharipov I.M.1, Khaliullin F.A.1, Klen E.E.1
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Мекемелер:
- Bashkir State Medical University
- Шығарылым: Том 26, № 7 (2023)
- Беттер: 26-33
- Бөлім: Pharmaceutical chemistry
- URL: https://bakhtiniada.ru/1560-9596/article/view/250527
- DOI: https://doi.org/10.29296/25877313-2023-07-04
- ID: 250527
Дәйексөз келтіру
Ашық рұқсат
Рұқсат берілді
Тек жазылушылар үшін
Аннотация
Objective – to study the parameters of binding of 3-methoxy-4-hydroxyphenylmethylidenehydrazides of 2-[3-methylxanthinyl-8-sulfanyl]-acetic acids with PDE 4A, 4B, 4C, 4D active centers, evaluate the effect of the thietane ring and select the most promising compound for synthesis
Material and methods: The objects of study are phosphodiesterase 4 and the structures of derivatives of thietanylxanthine. The studies were carried out by molecular docking. The structure of the synthesized compounds was confirmed by IR and NMR spectroscopy.
Results and conclusions. The inhibitory activity of 2-[3-methylxanthinyl-8-sulfanyl]acetic acid 3-methoxy-4-hydroxyphenyl-methylidenehydrazides against phosphodiesterases 4 was studied by molecular modeling. It was found that the studied molecules bind in the same site areas as native ligand roflumilast. Binding energies are comparable to roflumilast and for compound II even surpass it. The influence of the thietane and thietane 1-oxide cycles on the inhibitory activity was studied. The most promising compound II was synthesized.
Толық мәтін
##article.viewOnOriginalSite##Авторлар туралы
M. Urazbaev
Bashkir State Medical University
Хат алмасуға жауапты Автор.
Email: great-blood-mak@mail.ru
Ph.D. (Pharm.)
Ресей, UfaI. Sharipov
Bashkir State Medical University
Email: great-blood-mak@mail.ru
Ph.D. (Pharm.)
Ресей, UfaF. Khaliullin
Bashkir State Medical University
Email: great-blood-mak@mail.ru
Dr.Sc. (Pharm.)
Ресей, UfaE. Klen
Bashkir State Medical University
Email: great-blood-mak@mail.ru
Dr.Sc. (Pharm.)
Ресей, UfaӘдебиет тізімі
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