Синтез, будова та афінітет до рецепторів ЦНС 8-бром‑11-метил‑6-феніл‑11-піримідо[4,5-b][1,4] бензодіазепіну
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Дата
2022
Науковий керівник
Укладач
Редактор
Назва журналу
ISSN
E-ISSN
Назва тому
Видавець
Одеський національний університет імені І. І. Мечникова
Анотація
Взамодією 7-бром‑1-метил‑5-феніл‑1,3-дигідро‑2Н‑1,4-бенздіазепін‑2-ону з формамідом
в присутності хлорокису фосфору синтезовано 8-бром‑11-метил‑6-феніл‑11-піримідо[
4,5-b][1,4]бензодіазепін, будову якого підтверджено методами мас-спектрометрiї,
1Н ЯМР спектроскопії, а також рентгеноструктурним аналізом. Вивчено афінітет
синтезованої сполуки до центральних і периферичних бензодіазепінових рецепторів
ЦНС.
The purpose of this work is the synthesis of an annelated with pyrimidine system at position 2–3 of the diazepine cycle and the study of the affinity of the synthesized compound for the central benzodiazepine receptors (CBDR) and peripheral benzodiazepine receptors (PBDR) of the CNS, as well as, in the future, the study of pharmacological properties. The synthesis of 8-bromo‑11-methyl‑6-phenyl‑11-pyrimido[4,5-b][1,4]benzodiazepine II was carried out by heating 7-bromo‑1-methyl‑5-phenyl‑1,3-dihydro‑2Н‑1,4-benzodiazepin‑2-one I with formamide in a solution of phosphorus oxychloride. The structure of compound II was confirmed by mass spectrometry and 1H NMR spectroscopy, as well as by X‑ray diffraction analysis. 1Н NMR spectrum was recorded in ~2% solution of the compound in CDCl3 on the Bruker (300 MHz), internal standard TMS. Mass spectrum of the compound was obtained by electron impact on an mass spectrometer, “MX‑1321”, ionizing voltage 70 eV, ionizationchamber temperature 220 °C. The X‑ray diffraction study of the single crystal was carried out on a KUMA‑4CCD diffractometer using MoKa – radiation with ω-scanning at 100 K. The affinity of compound II to the central and peripheral benzodiazepine receptors of the CNS was studied by radioligand analysis. The experiment was carried out on nonpedigreed male rats with mass 180–220 g. The following radioligands were used: [3H]flumazenil (CBDR) and [3H]RK 11195 (PBDR). As a result of radioligand studies, it was found that compound II at a concentration of 1 10–6 M inhibits the specific binding of the radioligand [3H]flumazenil to CBDR by 43.7%, which indicates the presence of a moderate affinity for CBDR. It was also found that compound II at a concentration of 1 10–6 M inhibits the specific binding of the radioligand [3H]RK 11195 with PBDR by 3.7%, which indicates the practical absence of affinity for PBDR. The presence of a moderate affinity of compound II for CBDR and the selectivity of the binding of this compound to CBDR with respect to PBDR is of interest for further studies of this class of compounds as potential anxiolytics of a new type.
The purpose of this work is the synthesis of an annelated with pyrimidine system at position 2–3 of the diazepine cycle and the study of the affinity of the synthesized compound for the central benzodiazepine receptors (CBDR) and peripheral benzodiazepine receptors (PBDR) of the CNS, as well as, in the future, the study of pharmacological properties. The synthesis of 8-bromo‑11-methyl‑6-phenyl‑11-pyrimido[4,5-b][1,4]benzodiazepine II was carried out by heating 7-bromo‑1-methyl‑5-phenyl‑1,3-dihydro‑2Н‑1,4-benzodiazepin‑2-one I with formamide in a solution of phosphorus oxychloride. The structure of compound II was confirmed by mass spectrometry and 1H NMR spectroscopy, as well as by X‑ray diffraction analysis. 1Н NMR spectrum was recorded in ~2% solution of the compound in CDCl3 on the Bruker (300 MHz), internal standard TMS. Mass spectrum of the compound was obtained by electron impact on an mass spectrometer, “MX‑1321”, ionizing voltage 70 eV, ionizationchamber temperature 220 °C. The X‑ray diffraction study of the single crystal was carried out on a KUMA‑4CCD diffractometer using MoKa – radiation with ω-scanning at 100 K. The affinity of compound II to the central and peripheral benzodiazepine receptors of the CNS was studied by radioligand analysis. The experiment was carried out on nonpedigreed male rats with mass 180–220 g. The following radioligands were used: [3H]flumazenil (CBDR) and [3H]RK 11195 (PBDR). As a result of radioligand studies, it was found that compound II at a concentration of 1 10–6 M inhibits the specific binding of the radioligand [3H]flumazenil to CBDR by 43.7%, which indicates the presence of a moderate affinity for CBDR. It was also found that compound II at a concentration of 1 10–6 M inhibits the specific binding of the radioligand [3H]RK 11195 with PBDR by 3.7%, which indicates the practical absence of affinity for PBDR. The presence of a moderate affinity of compound II for CBDR and the selectivity of the binding of this compound to CBDR with respect to PBDR is of interest for further studies of this class of compounds as potential anxiolytics of a new type.
Опис
Ключові слова
7-бром‑1-метил‑5-феніл‑1,3-дигідро‑2Н‑1,4-бензодиазепін‑2-он, формамід, хлорокис фосфору, 8-бром‑11-метил‑6-феніл‑11-піримідо[4,5-b][1,4]бензодиазепін, бензодіазепінові рецептори, TSPO‑рецептори, афінітет, 7-bromo‑1-methyl‑5-phenyl‑1,3-dihydro‑2Н‑1,4-benzodiazepin‑2-one, formamide, phosphorus oxychloride, 8-bromo‑11-methyl‑6-phenyl‑11-pyrimido[4,5-b][1,4] benzodiazepine, X‑ray analysis, benzodiazepine receptors, TSPO receptors, affinity
Бібліографічний опис
Вісник Одеського національного університету = Odesa National University Herald