RU-2861478-C1 - USE OF COMPOUND 4-METHOXY-N-((1-(4-METHOXYPHENYL)-1H-IMIDAZO[1,2-a]INDOL-9-yl)METHYLENE)BENZENAMINIUM CHLORIDE AS ANTIDIABETIC AGENT FOR INSULIN-DEPENDENT DIABETES

RU2861478C1RU 2861478 C1RU2861478 C1RU 2861478C1RU-2861478-C1

Abstract

FIELD: pharmaceuticals; medicine. SUBSTANCE: proposed is the use of 4-methoxy-N-((1-(4-methoxyphenyl)-1H-imidazo[1,2-a]indol-9-yl)methylene)benzenaminium chloride or a pharmaceutically acceptable salt thereof as an antidiabetic agent for insulin-dependent diabetes mellitus. EFFECT: reducing mortality, body weight loss, hyperglycaemia, insulinaemia, serum C-reactive protein levels, disorders of carbohydrate, protein and lipid metabolism, morphological damage to the pancreas. 1 cl, 10 dwg, 16 tbl, 9 ex

Inventors

Chuian Elena Nikolaevna
Liventsov Stanislav Iurevich
Makalish Tatiana Pavlovna
Ravaeva Marina Iurevna
Belinskaia Daria Aleksandrovna
Galenko-Iaroshevskii Pavel Aleksandrovich
SUZDALEV KONSTANTIN FILIPPOVICH
Ishkhanian Narek Norairovich

Dates

Publication Date: 20260505
Application Date: 20251211

Claims (2)

The use of the compound 4-methoxy-N-((1-(4-methoxyphenyl)-1 H -imidazo[1,2- a ]indol-9-yl)methylene)benzeneammonium chloride of the formula
as an antidiabetic agent for insulin-dependent diabetes mellitus.

Description

The invention relates to medicine, in particular to experimental physiology, pharmacology and can be used for the prevention and treatment of hyperglycemia, absolute insulinopenia, disorders of carbohydrate, protein and fat metabolism, morphological damage to the pancreas in insulin-dependent diabetes mellitus (type 1 diabetes) and its complications. Diabetes mellitus is one of the most widespread non-communicable diseases, leading in terms of increasing morbidity, disability, and mortality in modern society. According to the International Diabetes Federation (IDF), this disease has become a serious global problem not only for public health but also for the economy. In 2023, the total number of people with diabetes reached 630 million, representing approximately 10% of the adult population worldwide. By 2030, this number is projected to increase to 643 million, and by 2045, this figure will rise to 783 million worldwide. According to WHO estimates, between 2005 and 2030, the mortality rate from diabetes will double, and in 2030 this disease will become the seventh leading cause of death worldwide, which will lead to medical, social and economic costs (Sun H. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045 / H. Sun, P. Saeedi, S. Karuranga [et al.] // Diabetes Research and Clinical Practice. - 2022. - Vol. 183. - P. 109119 doi: 10.1016/j.diabres.2021.109119; Ong K. L. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021 / K. L. Ong, L. K. Stafford, S. A. McLaughlin [et al.] // The Lancet. - 2023. - Vol. 402, No. 10397. - P. 203-234 doi: 10.1016/S0140-6736(23)01301-6). Diabetes mellitus is characterized by chronic hyperglycemia caused by absolute insulin deficiency in type 1 diabetes mellitus and pancreatic β-cell secretory defect combined with insulin resistance in type 2 diabetes mellitus. Research is aimed at finding the possibility of replacing the loss of pancreatic β-cells to achieve a stable euglycemic state [Beamish C.A., Strutt B.J., Arany E.J., Hill D.J. (2016) Insulin-positive, Glut2-low cells present within mouse pancreas exhibit lineage plasticity and are enriched within extra-islet endocrine cell clusters. Islets 8 (3): 65–82. https://doi.org/10.1080/19382014.2016.1162367]. Therefore, existing approaches to the treatment of diabetes mellitus are reduced to insulin replacement therapy in the case of absolute insulin deficiency in type 1 diabetes mellitus, or to the administration of agents that stimulate insulin secretion and increase the sensitivity of target cells to it in type 2 diabetes mellitus. In clinical practice, oral antidiabetic agents are used mainly nitrogen- and sulfur-containing organic compounds, such as sulfonylurea derivatives, biguanides, alpha-glucosidase inhibitors, etc., but to a greater extent for the treatment of type 2 diabetes and can cause side effects, especially with long-term use (Diabetes mellitus: diagnosis, treatment, prevention. Edited by I. I. Dedov and M. V. Shestakova. Moscow, 2011. - 808 p.; Spasov A. A., Petrov V. I., Cheplyaeva N. I., Lenskaya K. V. Fundamental principles of searching for drugs for the treatment of type 2 diabetes mellitus // Bulletin of the Russian Academy of Medical Sciences. - 2013 - No. 2. - P. 43-49). Therefore, given the growing prevalence of diabetes and its complications, the search for new drugs for the treatment of diabetes is very relevant. Indole compounds, both natural and synthetic, due to their structural diversity, a wide range of biological and pharmacological activity (anticonvulsant, anti-inflammatory, antimicrobial, antiviral, antifungal, anti-tuberculosis, antimalarial, antitumor, antihypertensive, analgesic, antidepressant, antioxidant, etc.), due to various mechanisms of action, are attracting more and more attention of organic chemists, pharmacists, researchers, their biological activity is being actively studied, preclinical and clinical studies of new compounds are being conducted (Srikanth Y, Reddy DH, Anusha VL, Dumala N, Viswanadh MK, Chakravarthi G, Nalluri BN, Yadagiri G, Ramakrishna K. Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review. Plants (Basel). 2025 Mar 6;14(5):827. doi: 10.3390/plants14050827; Kumari A, Singh RK Medicinal chemistry of indole derivatives: Current to future therapeutic prospects. Bioorg Chem. 2019 Aug;89:103021. doi: 10.1016/j.bioorg.2019.103021, PMID: 31176854; Zhu Y, Zhao J, Luo L, Gao Y, Bao H, Li P, Zhang H. Research progress of indole compounds with potential antidiabetic activity. Eur J Med Chem. 2021 Nov 5;223:113665. doi: 10.1016/j.ejmech.2021.113665. PMID: 34192642). Indole-based compounds may be promising resources for the development of new antidiabetic drugs (Zhu Y, Zhao J, Luo L, Gao Y, Bao H, Li P, Zhang H. Research p