Bis-methylamides of 1,2-dialkyl substituted imidazole-4,5-dicarboxylic acids: preparation and antinociceptive activity



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Abstract

BACKGROUND: Searching for substances with high analgesic activity is one of the main problems of modern medicine.

NMDA receptors present in all areas of the central nervous system responsible for reaction on pain stimulation. Moreover, peripheral glutamate receptors may be directly involved in the genesis of pain reactions. Therefore, it is of interest to search for new analgesics among NMDA receptor ligands.

AIM: To develop a preparative method of synthesis and to investigate the antinociceptive activity of 1,2-dialkyl imidazole-4,5-dicarboxylic acids (4,5-IDC) bis-methylamides on the example of 2-propyl-1-ethylimidazole-4,5-dicarboxylic acid bis-methylamide.

MATHERIALS AND METHODS: 1-Ethyl-2-propyl-4,5-IDC bis-methylamide was obtained using methods of organic synthesis. The Gaffner test of mechanical irritation of the base of the tail and the hot water tail-flick test in mice were selected to study the antinociceptive activity.

RESULTS: It was shown that the amidation of 2-substituted 4,5-IDC dimethyl ether followed by the alkylation of the resulting 2-substituted 4,5-IDC bis-amide is а preferable method of the two alternative for obtaining of 1,2-dialkyl 4,5-IDC bis-amides. It was shown that 1-ethyl-2-propyl-4,5-IDC bis-methylamide exhibits pronounced antinociceptive activity exceeding the activity of the comparative drugs analgin and ketorolac.

CONCLUSIONS: A preparative method for the synthesis of 1,2-dialkyl-4,5-IDC bis-amides is proposed. The dose-dependent antinociceptive activity of 1-ethyl-2-propyl-4,5-IDC bis-methylamide was shown. 1-ethyl-2-propyl-4,5-IDC bis-methylamide exhibits antinociceptive activity exceeding the activity of analgin and ketorolac.

About the authors

Polina Pavlovna Kropacheva

Санкт-Петербургский государственный технологический институт (технический университет); ФГБНУ «ИЭМ»

Author for correspondence.
Email: p.kropacheva99@mail.ru
ORCID iD: 0009-0005-1625-1108
Russian Federation, 190013, Россия, Санкт-Петербург, Московский проспект, дом 24-26/49 литера А; 197376, г. Санкт-Петербург, ул. Академика Павлова, д.12

Larisa Georgievna Kubarskaya

ФГБНУ «ИЭМ»; ФГБУ НКЦТ им. С.Н. Голикова ФМБА России

Email: larkub@yandex.ru
ORCID iD: 0000-0001-7622-0390
Scopus Author ID: 6506065231
Russian Federation, 197376, г. Санкт-Петербург, ул. Академика Павлова, д.12; 192019, Санкт-Петербург, ул. Бехтерева, д. 1

Mariia Alexandrovna Brusina

ФГБНУ «ИЭМ»

Email: mashasemen@gmail.com
ORCID iD: 0000-0001-8433-120X
Scopus Author ID: 57192072255
Russian Federation, 197376, г. Санкт-Петербург, ул. Академика Павлова, д.12

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