Synthesis and Analgesic Activity of 3-Arylamino-1,2-Dihydro-3H-1,4-Benzodiazepin-2-Ones

Павловский, В. И.; Ushakov, I. Yu.; Kabanova, T. A.; Khalimova, E. I.; Kravtsov, Victor Ch.; Андронати, С. А.

doi:10.1007/s11094-015-1335-4

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…Дію досліджуваних речовин вивчали за однаковим протоколом експерименту, сполуки вносили в розчин Кребса за 30 хв до реєстрації механічної активності препаратів. Кінцева концентрація похідних 3-заміщених 1,4-бенздіазепінонів в інкубаційному середовищі складала 10 -10 , 10 -8 і 10 -6 М. Синтез та властивості 3-заміщених 1,4-бенздіазепінонів описані в роботах [8,13,14].…”

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Features of the bradykinin-induced contraction of the gastric smooth muscle depending on the concentration of compounds based on 3-substituted-1,4-benzodiazepin-2-ones

2016

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П. Вірич, асп., О. Шелюк, канд. біол. наук, В. Мартинюк, д-р біол. наук Київський національний університет імені Тараса Шевченка, Київ, В. Павловський, д-р хім. наук Фізико-хімічний інститут імені О.В. Богатського НАН України, Одеса ОСОБЛИВОСТІ БРАДИКІНІН-ІНДУКОВАНОГО СКОРОЧЕННЯ ГЛАДЕНЬКИХ М'ЯЗІВ ШЛУНКУ ЗАЛЕЖНО ВІД КОНЦЕНТРАЦІЇ СПОЛУК НА ОСНОВІ 3-ЗАМІЩЕНИХ 1,4-БЕНЗДІАЗЕПІН-2-ОНІВ Досліджено вплив сполук на основі 3-заміщених-1,4-бензидіазепін-2-онів на скоротливу активність гладеньких м'язів шлунку щурів. Дія речовин МХ-1626, МХ-1775 схожа за патернами скорочення з конкурентними інгібітором брадикініну -des-Arg9-[Leu8]-Bradykinin acetate, що спостерігається у вигляді зростання нормованої швидкості скорочення по мірі зростання кількості брадикініну і характеризується помітним сповільненням першої фази скорочення. Найбільш ефективними 3-заміені 1,4-бенздіазепін-2-они виявились за низьких концентрацій брадикініну, при збільшенні якого їх дія зменшується. Ключові слова: гладенькі м'язи, механокінетичні параметри, 3-заміщені 1,4-бенздіазепін-2-они. Список використаних джерел.

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Section: вступunclassified

Features of the bradykinin-induced contraction of the gastric smooth muscle depending on the concentration of compounds based on 3-substituted-1,4-benzodiazepin-2-ones

2016

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“…Biochemical properties of 3-substituted 1,4-benzodiazepine are determined by features of their chemical structure. Using radicals with different chemical and physical properties to obtain derivates of basis molecules we created some compounds with affinity for specific biological targets [11]. These substances can mimic the βbend that is important for their biochemical activity [5].…”

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Effect of 3-substituted 1,4-benzodiazepin-2-ones on bradykinin-induced smooth muscle contraction

Virych¹,

Shelyuk²,

Kabanova³

2017

Ukr.Biochem.J.

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Analgesic effect of a bradykinin antagonist – a 1,4-benzodiazepine-2-one derivative

Aliforenko,

Bykov,

Bykova

et al. 2023

Bûll. sib. med.

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Aim. To study the analgesic effect of a new 1,4-benzodiazepine-2-one derivative (codenamed PAV-0056) in pain models in mice, its anti-inflammatory effect in experimental exudative inflammation in rats, and its potential ulcerogenic effect.Materials and methods. A 1,4-benzodiazepine-2-one derivative (codenamed PAV-0056) was orally administered in polyvinylpyrrolidone (PVP) solution to 192 CD-1 mice weighing 20–25 g and 140 Sprague – Dawley rats weighing 250–300 g. The analgesic effect of the PAV-0056 compound at a dose of 0.01, 0.1, and 1 mg / kg was studied in murine acute thermal pain models (hot plate test, hot water immersion tail-flick test), acute chemogenic pain models (formalin test), and visceral spasticity-related pain models (acetic acid-induced writhing test). The anti-inflammatory effect of PAV-0056 at doses of 0.01, 0.1, and 1 mg / kg was studied in an experimental rat model of inflammation induced by subplantar administration of bradykinin and histamine. The potential ulcerogenic effect was studied in intact rats, who were injected with PAV-0056 at doses of 1 and 50 mg / kg four times. The analgesic effect of the PAV-0056 compound was compared to that of diclofenac sodium at a dose of 10 mg / kg and tramadol at a dose of 20 mg / kg. Its anti-inflammatory and potential ulcerogenic effects were compared to those of diclofenac sodium at a dose of 10 mg / kg.Results. In the hot plate test, the PAV-0056 compound at a dose of 0.1 mg / kg increased response latency in mice by 36%, and at a dose of 1 mg / kg, it increased response latency by 46% (p < 0.05). In the tail-flick test, the PAV-0056 compound at a dose of 1 mg / kg increased response latency to heat stimulation in mice by 46% (p < 0.05). After subplantar administration of formalin, PAV-0056 at doses of 0.01–1 mg / kg had a pronounced analgesic effect, as shown by a decrease in the number of pain responses by 39–55% (p < 0.05). When mice were intraperitoneally injected with an acetic acid solution, the PAV-0056 compound at doses of 0.1 and 1 mg / kg reduced the frequency of writhings by 46 and 57%, respectively; at a dose of 0.1 mg / kg, it delayed the onset of the first writhing by 21% (p < 0.05). In experiments on rats, the PAV-0056 compound prevented the development of exudative inflammation induced by subplantar administration of bradykinin and did not have an anti-inflammatory effect in histamine-induced inflammation. PAV-0056 did not cause formation of gastric ulcers and gastric mucosal bleeding.Conclusion. A 1,4-benzodiazepine-2-one derivative, PAV-0056, has a pronounced analgesic effect in models of thermal, chemogenic, somatic, and visceral pain in a wide range of doses (0.01–1 mg / kg). Its analgesic effects are the same as those of diclofenac sodium at a dose of 10 mg / kg and tramadol at a dose of 20 mg / kg. The analgesic effect of the PAV-0056 compound is selective, depends little on suppression of inflammatory exudation, and is caused by bradykinin antagonism. This substance has low toxicity and does not damage the gastric mucosa.

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Synthesis and Analgesic Activity of 3-Arylamino-1,2-Dihydro-3H-1,4-Benzodiazepin-2-Ones

Cited by 3 publications

References 21 publications

Features of the bradykinin-induced contraction of the gastric smooth muscle depending on the concentration of compounds based on 3-substituted-1,4-benzodiazepin-2-ones

Features of the bradykinin-induced contraction of the gastric smooth muscle depending on the concentration of compounds based on 3-substituted-1,4-benzodiazepin-2-ones

Effect of 3-substituted 1,4-benzodiazepin-2-ones on bradykinin-induced smooth muscle contraction

Analgesic effect of a bradykinin antagonist – a 1,4-benzodiazepine-2-one derivative

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