RU2829463C1 - 2-((6-(4-BROMOPHENYL)-3-OXO-2,3-DIHYDROPYRIDAZIN-4-YL)AMINO)-4,5,6,7-TETRAHYDROBENZO[b]THIOPHENE-3-CARBONITRILE, HAVING ANTIMICROBIAL ACTIVITY WITH RESPECT TO CANDIDA ALBICANS - Google Patents
2-((6-(4-BROMOPHENYL)-3-OXO-2,3-DIHYDROPYRIDAZIN-4-YL)AMINO)-4,5,6,7-TETRAHYDROBENZO[b]THIOPHENE-3-CARBONITRILE, HAVING ANTIMICROBIAL ACTIVITY WITH RESPECT TO CANDIDA ALBICANS Download PDFInfo
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- -1 2-((6-(4-BROMOPHENYL)-3-OXO-2,3-DIHYDROPYRIDAZIN-4-YL)AMINO)-4,5,6,7-TETRAHYDROBENZO[b]THIOPHENE-3-CARBONITRILE Chemical compound 0.000 title claims abstract description 9
- 230000000845 anti-microbial effect Effects 0.000 title claims abstract description 5
- 241000222122 Candida albicans Species 0.000 title description 5
- 229940095731 candida albicans Drugs 0.000 title description 4
- 231100000053 low toxicity Toxicity 0.000 abstract description 5
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract description 3
- 239000013543 active substance Substances 0.000 abstract description 2
- 239000000126 substance Substances 0.000 abstract description 2
- AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical class OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 abstract 1
- 229940125904 compound 1 Drugs 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 230000000843 anti-fungal effect Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 244000005700 microbiome Species 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- DOMXUEMWDBAQBQ-WEVVVXLNSA-N terbinafine Chemical compound C1=CC=C2C(CN(C\C=C\C#CC(C)(C)C)C)=CC=CC2=C1 DOMXUEMWDBAQBQ-WEVVVXLNSA-N 0.000 description 3
- 229960002722 terbinafine Drugs 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- 206010007134 Candida infections Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 201000003984 candidiasis Diseases 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Abstract
Description
Изобретение относится к области органической химии, к новым биологически активным веществам класса замещенных пиридазин-3(2H/)-онов, а именно к 2-((6-(4-бромфенил)-3-оксо-2,3-дигидропиридазин-4-ил)амино)-4,5,6,7-тетрагидробензо[b]тиофен-3-карбонитрилу формулы:The invention relates to the field of organic chemistry, to new biologically active substances of the class of substituted pyridazin-3(2H/)-ones, namely to 2-((6-(4-bromophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile of the formula:
который обладает противомикробной активностью, что позволяет предположить его использование в медицине в качестве лекарственного средства с противогрибковыми свойствами и низкой токсичностью.which has antimicrobial activity, which suggests its use in medicine as a drug with antifungal properties and low toxicity.
Аналогом по структуре заявляемому соединению является этиловый эфир 2-[(3-оксо-6-фенил-2-этил-2,3-дигидропиридазин-4-ил)амино]-4,5,6,7-тетрагидробензо[b]тиофен-3-карбоновой кислоты [S.A. Shipilovskikh, А.Е. Rubtsov, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 12, pp. 1853-1855, doi: 10.1134/S1070428014120288] формулы:A structural analogue of the claimed compound is ethyl ester of 2-[(3-oxo-6-phenyl-2-ethyl-2,3-dihydropyridazin-4-yl)amino]-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid [S.A. Shipilovskikh, A.E. Rubtsov, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 12, pp. 1853-1855, doi: 10.1134/S1070428014120288] of the formula:
Эталоном сравнения биологической активности был выбран тербинафин формулы:Terbinafine of the formula was chosen as the standard for comparison of biological activity:
который широко применяется в лечебной практике и является аналогом по действию [Машковский М.Д. Лекарственные средства. - 16-е изд., перераб., испр. и доп. - М.: Новая волна, 2012. - с. 925].which is widely used in medical practice and is similar in action to [Mashkovsky M.D. Medicines. - 16th ed., revised, corrected and supplemented. - M.: Novaya Volna, 2012. - p. 925].
Задачей изобретения является расширение арсенала противогрибковых средств по отношению к кандидозу, в частности разработка средства, обладающего выраженной противогрибковой активностью по отношению к Candida albicans и низкой токсичностью.The objective of the invention is to expand the arsenal of antifungal agents against candidiasis, in particular to develop an agent that has pronounced antifungal activity against Candida albicans and low toxicity.
Поставленная задача достигается получением 2-((6-(4-бромфенил)-3-оксо-2,3-дигидропиридазин-4-ил)амино)-4,5,6,7-тетрагидробензо[b]тиофен-3-карбонитрила, который обладает противогрибковой активностью.The set task is achieved by obtaining 2-((6-(4-bromophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile, which has antifungal activity.
Заявляемое соединение 1 синтезируют взаимодействием 2-((5-(4-бромфенил)-2-оксофуран-3(2H)-илиден)амино)-4,5,6,7-тетрагидробензо[b]тиофен-3-карбонитрила с гидразином. Реакция протекает в диоксане при перемешивании и температуре 60°С в течение 1 часа, с последующим удалением растворителя и выделением целевого продукта известными методами по схеме:The claimed compound 1 is synthesized by the reaction of 2-((5-(4-bromophenyl)-2-oxofuran-3(2H)-ylidene)amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile with hydrazine. The reaction takes place in dioxane with stirring and a temperature of 60°C for 1 hour, followed by removal of the solvent and isolation of the target product by known methods according to the scheme:
Получение соединения 1: к 412 мг (0,001 моль) 2-((5-(4-бромфенил)-2-оксофуран-3(2H)-илиден)амино)-4,5,6,7-тетрагидробензо[b]тиофен-3-карбонитрила добавили 5 мл диоксана, 60 мг (0,0012 моль) гидразина гидрата и перемешивали в течение 1 ч при 60°С. Раствор охлаждали до 0°С, образовавшийся осадок отфильтровывали и перекристаллизовывали из этанола.Preparation of compound 1: 5 ml of dioxane and 60 mg (0.0012 mol) of hydrazine hydrate were added to 412 mg (0.001 mol) of 2-((5-(4-bromophenyl)-2-oxofuran-3(2H)-ylidene)amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile and the mixture was stirred for 1 h at 60°C. The solution was cooled to 0°C, the resulting precipitate was filtered off and recrystallized from ethanol.
Выход 320 мг (75%), желтые кристаллы, т. пл. 212-214°С (этанол). Спектр 1Н ЯМР (ДМСО-d6), δ, м.д.: 1.81 м (4Н, 2СН2), 2.59 м (2Н, СН2), 2.68 м (2Н, СН2), 6.99 с (1H, СН), 7.65 м (2Н, Наром), 7.74 м (2Н, Наром), 9.49 уш. с. (1H, NH), 13.23 уш. с. (1Н, NH). Спектр 13С ЯМР (ДМСО-d6), δ, м.д.: 22.0, 23.1, 24.4, 24.5, 101.6, 114.3, 122.9, 127.8, 128.6, 131.5, 132.2, 133.8, 135.6, 141.1, 145.1, 149.0, 156.4. Найдено, %: С 53.42; Н 3.55; N 13.13; S 7.52. C19Hi5BrN4OS. Рассчитано, %: С 53.40; Н 3.54; N 13.11; S 7.50.Yield 320 mg (75%), yellow crystals, mp 212-214°C (ethanol). 1 H NMR (DMSO-d 6 ), δ, ppm: 1.81 m (4H, 2CH 2 ), 2.59 m (2H, CH 2 ), 2.68 m (2H, CH 2 ), 6.99 s (1H, CH), 7.65 m (2H, Harom ), 7.74 m (2H, Harom ), 9.49 br s (1H, NH), 13.23 br s (1H, NH). 13C NMR spectrum (DMSO-d 6 ), δ, ppm: 22.0, 23.1, 24.4, 24.5, 101.6, 114.3, 122.9, 127.8, 128.6, 131.5, 132.2, 133.8, 135.6, 141.1, 145.1, 149.0, 156.4. Found, %: C 53.42; H 3.55; N 13.13; S 7.52. C 19 Hi 5 BrN 4 OS. Calculated, %: C 53.40; H 3.54; N 13.11; S 7.50.
Полученное соединение 1 представляет собой оранжевое кристаллическое вещество, растворимое в ДМСО, ацетоне, не растворимое в воде и гексане.The obtained compound 1 is an orange crystalline substance, soluble in DMSO, acetone, insoluble in water and hexane.
Пример 2. Острую токсичность (ЛД50, мг/мл) соединения 1 определяли по методу Г.Н. Першина [Першин Г.Н. Методы экспериментальной химиотерапии // М., С. 100, 109-117 (1971)]. Соединение 1 вводили внутрибрюшинно белым мышам массой 16-18 г в виде взвеси в 2% крахмальной слизи и наблюдали за поведением и гибелью животных в течение 10 суток. Для исследуемого соединения 1 ЛД50 составляет >1500 мг/кг.Example 2. Acute toxicity (LD 50 , mg/ml) of compound 1 was determined by the method of G.N. Pershin [Pershin G.N. Methods of experimental chemotherapy // Moscow, pp. 100, 109-117 (1971)]. Compound 1 was administered intraperitoneally to white mice weighing 16-18 g as a suspension in 2% starch mucus and the behavior and mortality of the animals were observed for 10 days. For the studied compound 1, LD 50 is >1500 mg/kg.
Согласно классификации токсичности препаратов соединение 1 относится к V классу практически нетоксичных препаратов [Измеров Н.Ф., Саноцкий И.В., Сидоров К.К. Параметры токсикометрии промышленных ядов при однократном воздействии: Справочник. М., 1977. - с. 196].According to the classification of drug toxicity, compound 1 belongs to class V of practically non-toxic drugs [Izmerov N.F., Sanotsky I.V., Sidorov K.K. Toximetry parameters of industrial poisons with a single exposure: Handbook. Moscow, 1977. - p. 196].
Пример 3. Для характеристики противогрибковой активности соединений использовали стандартные параметры: минимальная подавляющая концентрация (МПК), которую определяли модифицированным методом двукратных серийных разведений [МУК 4.2.1890-04 Определение чувствительности микроорганизмов к антибактериальным препаратам] и минимальная бактерицидная концентрация (МБК) [Медицинские лабораторные технологии: Руководство по клинической лабораторной диагностике, п/р Каприщенко, 2013, Т 2, стр. 407]. Тесты проводили с использованием культуры модельного микроорганизма Candida albicans АТСС 10231 (Всероссийская коллекция патогенных микроорганизмов) на питательной среде Мюллера-Хинтона с добавлением 0,4% глюкозы в 96-луночных полистироловых планшетах. Концентрация микроорганизмов в лунках перед началом культивирования составляла 5*105 КОЕ/мл. Культивирование проводили при 37°С без перемешивания. Определение МПК и высевы для определения МБК производили через 24 ч. Исследуемое соединение растворяли в диметилсульфоксиде (ДМСО) в концентрации 20 мг/мл до полного растворения. Максимальная действующая концентрация составляла 1000 мкг/мл. Эффект сравнивали с тербинафином.Example 3. To characterize the antifungal activity of the compounds, the following standard parameters were used: the minimum inhibitory concentration (MIC), which was determined by a modified method of two-fold serial dilutions [MUK 4.2.1890-04 Determination of the sensitivity of microorganisms to antibacterial drugs] and the minimum bactericidal concentration (MBC) [Medical Laboratory Technologies: Guide to Clinical Laboratory Diagnostics, edited by Kaprishchenko, 2013, Vol. 2, p. 407]. The tests were carried out using a culture of the model microorganism Candida albicans ATCC 10231 (All-Russian Collection of Pathogenic Microorganisms) on Mueller-Hinton nutrient medium with the addition of 0.4% glucose in 96-well polystyrene plates. The concentration of microorganisms in the wells before cultivation was 5*10 5 CFU/ml. Cultivation was carried out at 37°C without stirring. Determination of MIC and inoculation for determination of MBC were carried out after 24 h. The test compound was dissolved in dimethyl sulfoxide (DMSO) at a concentration of 20 mg/ml until complete dissolution. The maximum effective concentration was 1000 μg/ml. The effect was compared with terbinafine.
Результаты испытаний представлены в таблице:The test results are presented in the table:
Как видно из таблицы, заявляемое соединение 1 обладает выраженной противогрибковой активностью на уровне препарата сравнения (тербинафин) по отношению к Candida albicans АТСС 10231, а также показывает низкую токсичность. Таким образом, 2-((6-(4-бромфенил)-3-оксо-2,3-дигидропиридазин-4-ил)амино)-4,5,6,7-тетрагидробензо[b]тиофен-3-карбонитрил 1 проявляет выраженную активность по сравнению с эталоном сравнения, что делает возможным его использование для создания новых лекарственных средств целенаправленного действия.As can be seen from the table, the claimed compound 1 has a pronounced antifungal activity at the level of the reference drug (terbinafine) in relation to Candida albicans ATCC 10231, and also shows low toxicity. Thus, 2-((6-(4-bromophenyl)-3-oxo-2,3-dihydropyridazin-4-yl)amino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile 1 exhibits pronounced activity compared to the reference standard, which makes it possible to use it to create new drugs with targeted action.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| RU2763735C1 (en) * | 2021-06-29 | 2021-12-30 | Федеральное государственное автономное образовательное учреждение высшего образования "Пермский государственный национальный исследовательский университет" (ПГНИУ) | Application of antimicrobial agent for golden staphylococcus with multiple drug resistance based on 2-((4-r1-5-r2-3-(ethoxicarbonyl)thiophene-2-yl)amino-4-r3-oxo-enoic acids |
| RU2766564C1 (en) * | 2021-06-29 | 2022-03-15 | Федеральное государственное автономное образовательное учреждение высшего образования "Пермский государственный национальный исследовательский университет" (ПГНИУ) | USE OF AN ANTIFUNGAL AGENT BASED ON ETHYL ESTER OF 2-[(5-(4-METHOXYPHENYL)-2-OXOFURAN-3(2H)-YLIDENE)AMINO]-4,5,6,7-TETRAHYDROBENZO[b]THIOPHENE-3-CARBOXYLIC ACID |
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2763735C1 (en) * | 2021-06-29 | 2021-12-30 | Федеральное государственное автономное образовательное учреждение высшего образования "Пермский государственный национальный исследовательский университет" (ПГНИУ) | Application of antimicrobial agent for golden staphylococcus with multiple drug resistance based on 2-((4-r1-5-r2-3-(ethoxicarbonyl)thiophene-2-yl)amino-4-r3-oxo-enoic acids |
| RU2766564C1 (en) * | 2021-06-29 | 2022-03-15 | Федеральное государственное автономное образовательное учреждение высшего образования "Пермский государственный национальный исследовательский университет" (ПГНИУ) | USE OF AN ANTIFUNGAL AGENT BASED ON ETHYL ESTER OF 2-[(5-(4-METHOXYPHENYL)-2-OXOFURAN-3(2H)-YLIDENE)AMINO]-4,5,6,7-TETRAHYDROBENZO[b]THIOPHENE-3-CARBOXYLIC ACID |
Non-Patent Citations (2)
| Title |
|---|
| Shams, HodaZaki et al. "Design and synthesis of novel antimicrobial acyclic and heterocyclic dyes and their precursors for dyeing and/or textile finishing based on 2-n-acylamino-4,5,6,7-tetrahydrobenzo[b]thiophene systems", Molecules, 2011, vol. 16, No 8, p. 6271 - 6305. * |
| Shipilovskikh, S. A.; Rubtsov, A. E. "Chemistry of iminofurans. Recyclization of ethyl 2-[2-oxo-5-phenylfuran-3(2H)-ylideneamino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate by the action of hydrazines", Russian Journal of Organic Chemistry, 2014, vol. 50, No 12, p. 1853 - 1855. Шипиловских Сергей Александрович "Синтез и химические превращения замещенных 3-(тиофен-2-ил)имино-3Н-фуран-2-онов", Диссертация, Пермь, 2015, 173 с. * |
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