Действующие проекты

• Медицинская химия, дизайн и биологическая активность малых молекул

Проект РНФ 22-13-00005“Расширение химического инструментария для целенаправленной деградации белков”

Терапевтические подходы к целому ряду заболеваний (прежде всего, онкологических) традиционно основаны на снижении уровней (ингибировании) различных белков (ферментов) моноклональными антителами (MAB) или низкомолекулярными ингибиторами (SMI). Оба этих подхода обременены недостатками, снижающими продуктивность фармацевтической промышленности в создании новых препаратов. Это, прежде всего, чрезвычайная дороговизна MAB и высокий риск провала программ по разработке SMI, особенно на поздних стадиях клинических исследований, ввиду возникновения нежелательных побочных явлений. Около 20 лет назад в академической среде родилась идея использовать – как альтернативу MAB и SMI – естественную способность наших клеток избавляться от ненужных или дефектных белков за счет убиквитин-зависимой протеасомной деградации таких белков. Подобный подход к деградации нежелаемых белков получил название PROTAC (от английского “PROteolysis TArgeting Chimeras). Сегодня в эту технологию инвестируются миллиарды долларов, практически любая крупная фармацевтическая компания (среди них Roche, Pfizer, Merck, Novartis и GlaxoSmithKline) ведет исследования в этой области, а сегодняшнее состояние дел в сфере PROTAC зачастую называют «золотой лихорадкой».

Наши исследования по поиску новых, потенциальных лигандов убиквитин-лигазы CRBN, применяемых в создании молекул PROTACи новых, эффективныхдеградаторов белков ведутся совместноcлабораторией профессора Маркуса Хартманна (Институт биологии развития Макса Планка) ицентром медицинской химии под руководством Александра Бунева (Тольяттинский университет).

• Мультикомпонентные реакции

Международный проект РФФИ20-53-56002“Использование возможностей постконденсационных модификаций продуктов реакции GBB (Гребке-Блакберна-Бьенеме) в конструировании новых молекулярных скаффолдов для дизайна биологически активных веществ”

Многокомпонентные реакции (МКР) представляют собой непревзойденный по своей эффективности инструмент для быстрого и высокоэффективного конструирования сложных органических молекул. В сочетании с так называемыми постконденсационными модификациями (заранее запланированными реакциями второго уровня, в которые вовлекаются попарно реакционноспособные группы в составе продукта МКР) наращивание молекулярной сложности получаемых структур происходит с удивительной быстротой. И эффективность конструирования новых молекул, и быстрота наращивания молекулярной сложности имеют самостоятельную ценность в поиске биологически активных веществ и новых лекарств, поскольку все это позволяет работать в не занятых никем ранее областях химического пространства, что обеспечивает уникальность структур, их биологического профиля, а также облегчает в конечном итоге защиту прав интеллектуальной собственности.

• Использование химии диазосоединений в скаффолд-ориентированном синтезе

Проект РНФ 20-13-00024“Диазогетероциклы: новая платформа для скаффолд-ориентированного синтеза”

Основной целью настоящего направления является разработка новых, удобных методов построения и модификации гетероциклических скаффолдов, представляющих интерес для медицинской химии. Разрабатываемый нами комплекс подходов основан на использовании диазогетероциклических реагентов различной природы в ряде химических превращений, приводящих к образованию структурно-разнообразных гетероциклических производных на основе привилегированных скаффолдов. Учитывая широчайшие синтетические возможности, обусловленные огромным разнообразием путей превращения диазомолекул, заполнение пробелов в этой области органической химии и валидация ее как новой платформы для синтеза потенциально биоактивных, подобных лекарству (‘drug-like’) и подобных природным соединениям (‘natural-like’), гетероциклических соединений, представляет чрезвычайно актуальную проблему.

Публикации

2024

1. Kantin, G.; Sapegin, A.; Dar’in, D. 5‑Diazo Dihydrouracils: Preparation and Some Transformations. J. Org. Chem. 2024, published on line. DOI: 10.1021/acs.joc.4c01973
2. Paramonova, P.; Lebedev, R.; Sokolov, A.; Dar'in, D.; Kanov, E.; Murtazina, R.; Gainetdinov, R.; Kalinin, S.; Bakulina, O., Azide-based in situ preparation of fused heterocyclic imines and their multicomponent reactions. Org Biomol Chem 2024, 22, (41), 8328-8336
3. Paramonova, P.; Eliseev, I.; Dar'in, D.; Bakulina, O., Imines with rare alpha-heteroatom substituted amine components generated in situ via the Staudinger/aza-Wittig tandem reaction and their application in multicomponent reactions. Org Biomol Chem 2024, 22, (8), 1733-1744
4. Karchuganova, E.; Martynova, S.; Kalinin, S.; Angeli, A.; Dar'in, D.; Vullo, D.; Supuran, C. T.; Bakulina, O., Direct assembly of N-sulfamoyl lactam scaffolds bearing a zinc-binding group for inhibiting metalloenzymes based on desymmetrization of sulfamide and the Castagnoli-Cushman reaction. Tetrahedron 2024, 154
5. Guranova, N.; Bakulina, O.; Kantin, G.; Dar'in, D., Concise Approach towards Tetramic Acid Derivatives via Ugi Reaction/Dieckmann Cyclization Sequence. ChemistrySelect 2024, 9, (8)
6. Bakulina, O. Y.; Sapegin, A. V.; Yarovaya, O. I., Second All-Russian School on Medicinal Chemistry for Young Scientists. Russian Journal of Organic Chemistry 2024, 59, (12), 2038-2062
7. Malkova, K.; Tatarinov, I.; Kantin, G.; Dar’in, D. Utilizing Allenic Acids and Heterocyclic Diazo Compounds in the Synthesis of Polysubstituted Spirocyclic Butenolides and β‑Methylidene 2‑Furanones. J. Org. Chem. 2024, 89(4), 2782–2786.
8. Krivovicheva, V.; Lyutin, I.; Kantin, G.; Dar’in, D. Access to Spiro Bis-β-lactams via a Metal-Free Microwave-Assisted Wolff Rearrangement/Staudinger [2+2] Cycloaddition Cascade Involving 3‑Diazotetramic Acids and Imines. J. Org. Chem. 2024, 89(5), 3585–3589
9. Yanovich, A.; Vepreva, A.; Malkova, K.; Kantin, G.; Dar’in, D. Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides. Beilstein J. Org. Chem. 2024, 20, 561–569
10. Kashina, M. V.; Luzyanin,K. V.; Dar’in, D. V.; Bezzubov, S. I.; Kinzhalov M. A. Phosphorescent Cyclometalated Palladium(II) and Platinum(II) Complexes Derived from Diaminocarbene Precursors. Inorg. Chem. 2024, 63, 5315−5319
11. Dar'in, D.; Kantin, G.; Glushakova, D.; Sharoyko, V.; Krasavin, M. Diazo Tetramic Acids Provide Access to Natural-Like Spirocyclic Δα,β-Butenolides through Rh(II)-catalyzed O-H Insertion/Base-Promoted Cyclization. J. Org. Chem., 2024, 89, 11, 7366–7375

 2023

1. Lukin, A.; Komarova, K.; Vinogradova, L.; Rogacheva, E.; Kraeva, L.; Krasavin, M. Synthesis and antibacterial evaluation of ciprofloxacin congeners with spirocyclic amine periphery. Int. J. Mol. Sci. 2023, 24, 954
2. Dar'in, D.; Kantin, G.; Glushakova, D.; Sharoyko, V.; Krasavin, M. Diazo Tetramic Acids Provide Access to Natural-Like Spirocyclic Δα,β-Butenolides through Rh(II)-catalyzed O-H Insertion/Base-Promoted Cyclization. J. Org. Chem., accepted 26.12.2022
3. Krivovicheva, V.; Bubyrev, A.; Kalinin, S.; Dar'in, D.; Gureev, M.; Vullo, D.; Krasavin, M.; Korsakov, M.; Supuran, C. T. A new way of synthesizing heterocyclic primary sulfonamide probes for carbonic anhydrase. Mendeleev Commun., accepted 23.12.2022
4. Krasavin, M.; Adamchik, M.; Bubyrev, A.; Heim, C.; Maiwald, S.; Zhukovsky, D.; Zhmurov, P.; Bunev, A.; Hartmann, M. D. Synthesis of novel glutarimide ligands for the E3 ligase substrate receptor Cereblon (CRBN): investigation of their binding mode and antiproliferative effects against myeloma cell lines. Eur. J. Med. Chem. 2023, 246, 114990
5. Lukin, A.; Vinogradova, L.; Komarova, K.; Krasavin, M. Spirocyclic azetidines for drug discovery: novel Boc-protected 7'H-spiro[azetidine-3,5'-furo[3,4-d]pyrimidines]. Mendeleev Commun. 2022, accepted 10.11.2022
6. Lukin, A.; Vinogradova, L.; Komarova, K.; Kalinin, S.; Krasavin, M. Synthesis of 1-oxa-9-azaspiro[5.5]undecane-9-sulfonamides bearing a diverse molecular periphery and a rare zinc-binding group for carbonic anhydrase interrogation. Mendeleev Commun., accepted 01.11.2022
7. Solovyev, I.; Dar'in, D.; Krasavin, M. Synthetic enabling of spirocyclic oxetane fatty acid mimetics based on 1-oxa-6,7-diazaspiro[3.4]oct-7-en-5-one scaffold via diazo chemistry. Mendeleev Commun. 2023, 33, 21-23
8. Lukin, A.; Komarova, K.; Vinogradova, L.; Rogacheva, E.; Kraeva, L.; Dogonadze, M.; Vinogradova, T.; Krasavin, M. Urea derivatives of spirocyclic piperidines endowed with antibacterial activity. Mendeleev Commun. 2023, 33, 109-111
9. Adamchik, M.; Bubyrev, A.; Zhukovsky, D.; Zhmurov, P.; Bunev, A.; Krasavin, M. Synthesis of novel glutarimide derivatives via the Michael addition of (hetero)aromatic thiols: pronounced effect of sulfur oxidation on cytotoxicity towards multiple myeloma cell lines. Mendeleev Commun. 2023, 33, 67-69
10. Sibinčić, N.; Kalinin, S.; Sharoyko, V.; Efimova, J.; Gasilina, O. A.; Korsakov, M.; Gureev, M.; Krasavin, M. A Series of Trifluoromethylisoxazolyl- and Trifluoromethylpyrazolyl-Substituted (Hetero)aromatic Sulfonamide Carbonic Anhydrase Inhibitors: Synthesis and Convenient Prioritization Workflow for Further In Vivo studies. Med. Chem. 2023, 19, 193-210
11. Kazantsev, A.; Rodionov, I. A.; Bakulina, O.; Kantin, G.; Dar'in, D.; Krasavin, M., Catalyst Loading Controls Chemoselectivity: Unusual Effect in Rhodium(II) Carbene Insertion Reactions with Tetrahydrofuran. Catalysts 2023, 13, (2), 12
12. Moshnenko, N.; Kazantsev, A.; Chupakhin, E.; Bakulina, O.; Dar'in, D., Synthetic Routes to Approved Drugs Containing a Spirocycle. Molecules 2023, 28, (10), 47
13. Levashova, E.; Adamchik, M.; Kantin, G.; Dar’in, D. Chemo- and Diastereoselective Entries into All-Carbon α-Quaternary Aldehydes via C–C Insertion of 4-Diazoisoquinolin-3-ones into C–CHO Bonds. J. Org. Chem. 2023, 88, 15, 11217–11226
14. Peshkov, A.A.; Gapanenok, D.; Puzyk, A.; Amire, N.; Novikov, A.S.; Martynova, S.D.; Kalinin, S.; Dar’in, D.; Peshkov, V.A.; Krasavin, M. Substrate-Controlled Three-Component Synthesis of Diverse Fused Heterocycles. J. Org. Chem. 2023, 88(15), 10508–10524
15. Lukin, A.; Nichugovskaya, A.; Vinogradova, L.; Komarova, K.; Balalaie, S.; Dar’in, D.; Krasavin, M. Convenient, DBU-promoted anti-Markovnikov hydration of 2-methyl-1-(3-arylprop-2-yn-1-yl)-1H-imidazoles in wet NMP. Mendeleev Commun. 2023, 33(4), 455-457
16. Rezaei-Gohar, M.; Amiri, K.; Aghaie, K.; Nayebzadeh, B.; Ariafard, A.; Shiri, F.; Rominger, F.; Dar’in, D.; Krasavin, M.; Balalaie, S. Domino Cyclization Reaction of o-Diisocyanoarenes for the Synthesis of Imidazo[1,2-a]pyridinobenzimidazole Backbones. Org. Lett. 2023, 25(30), 5682–5686.
17. Kantin, G.; Golubev, P.; Sapegin, A.; Bunev, A.; Dar’in, D. N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction. Beilstein J. Org. Chem. 2023, 19, 1841–1848
18. Shcherbakov, N.; Kotikova, P.; Chikunova, E.; Dar'in, D.; Kukushkin, V.; Dubovtsev, A. Gold-Catalyzed Annulation of Ynamides with Aminocarbonyls as a Route to 2-Aminoquinolines Diversely Substituted at the 4th-Position. Adv. Synth. Catal. 2023, 365, 2428-2434
19. Malkova, K.; Bubyrev, A.; Kalinin, S.; Dar’in, D. Facile access to 3-sulfonylquinolines via Knoevenagel condensation/aza-Wittig reaction cascade involving ortho-azidobenzaldehydes and β-ketosulfonamides and sulfones. Beilstein J. Org. Chem. 2023, 19, 800–807
20. Shevalev R.; Sapegin A.; Bischof L.; Bunev A.; Grigor'eva O.; Kantin G.; Kalinin S.; Hartmann M.D. Discovery and characterization of potent spiro-isoxazole-based cereblon ligands with a novel binding mode.  Eur. J. Med. Chem. 2024, 270(15), 116328
21. Aghaie K.; Amiri K.; Rezaei-Gohar M.; Rominger F.; Dar’in D.; Sapegin, A.; Balalaie S. Transition-metal-free intramolecular double hydrofunctionalization of alkyne to access 6/7/5-fused heterocyclic skeletons. Chem. Commun., 2024, 60, 2661-2664
22. Kasparavichius M.G., Weber D.I.,  Bunev A.S., Sapegin, A.V. Novel 2-amino-substituted (thio)morpholine-3,5-diones: synthesis and cytotoxicity studies. Mendeleev Commun. 2024, 34(2), 262-264
23. Smirnova, D.S.; Sharoiko, V.V.; Kalinin S.A.;  Sapegin, A.V. The synthesis and study of carbonic anhydrase activity of sulfonamide-containing dibenzo[1,4]thiazepines. Chem. Heterocycle. Cmpd. 2023, 59(11/12), 833–838
24. Rastorgueva, M.S, Weber D.I., Sapegin, A.V. Hydrated imidazoline ring expansion reaction in 2,3-dihydro-9H-dibenzo[b,f]imidazo[2,1-d][1,5]oxazocinone derivatives. Chem. Heterocycle. Cmpd. 2023, 59(9/10), 692–697.
25. Kalinin, S., Sapegin, A. Ring Expansion Reactions through Intramolecular Transamidation. Eur. J. Org. Chem., 2023, 26(44), e202300754

 2022

1. Moshnenko, N.; Kazantsev, A.; Bakulina, O.; Dar'in, D.; Krasavin, M. The Use of Aryl-Substituted Homophthalic Anhydrides in the Castagnoli–Cushman Reaction Provides Access to Novel Tetrahydroisoquinolone Carboxylic Acid Bearing an All-Carbon Quaternary Stereogenic Center. Molecules 2022, 27, 8462
2. Lebedev, R.; Dar'in, D.; Kantin, G.; Bakulina, O.; Krasavin, M. One-pot sequence of Staudinger/aza-Wittig/Castagnoli-Cushman reactions provides facile access to novel natural-like polycyclic ring system. Molecules 2022, 27, 8130
3. Paramonova, P.; Lebedev, R.; Bakulina, O.; Dar'in, D.; Krasavin, M. In situ generation of imines by Staudinger/aza-Wittig tandem combined with thermally induced Wolff rearrangement for one-pot three-component β-lactam synthesis. Org. Biomol. Chem. 2022, 20, 9679-9683
4. Vepreva, A.; Yanovich, A.; Dar'in, D.; Kantin, G.; Bunev, A.; Krasavin, M. Novel spirocyclic scaffold accessed via tandem Claisen rearrangement – intramolecular oxa-Michael addition. Beilstein J. Org. Chem. 2022, 18, 1649-1655
5. Malkova, K.; Bubyrev, A.; Krivovicheva, V.; Dar'in, D.; Bunev, A.; Krasavin, M. Novel Bis-Triazole Scaffold Accessed via Two Tandem [3+2] Cycloaddition Events Including an Uncatalyzed, Room-Temperature Azide-Alkyne Click Reaction. Beilstein J. Org. Chem. 2022, 18, 1636–1641
6. Krasavin, M.; Lukin, A.; Sukhanov, I.; Gerasimov, A.; Kuvarzin, S.; Efimova, E. V.; Dorofeikova, M.; Nichugovaskaya, A.; Matveev, A.; Onokhin, K.; Zakharov, K.; Gureev, M.; Gainetdinov, R. R. Discovery of Trace Amine Associated Receptor 1 (TAAR1) Ag-onist 2-(5-(4'-Chloro-[1,1'-biphenyl]-4-yl)-4H-1,2,4-triazol-3-yl)ethan-1-amine (LK00764) for the Treatment of Psychotic Disorders. Biomolecules 2022, 12, 1650
7. Krivovicheva, V.; Bubyrev, A.; Kalinin, S.; Dar'in, D.; Krasavin, M. Synthetic Exploration of Novel Sulfamoyl Cyanide N-Oxides in Heterocycle Synthesis. Eur. J. Org. Chem. 2022, e202201162
8. Malkova, K.; Bubyrev, A.; Balalaie, S.; Dar'in, D.; Krasavin, M. Metal-free synthetic approaches to 1,5-disubstituted 1,2,3-triazoles. Tetrahedron Lett. 2022, 112, 154228
9. Guranova, N.; Yakovleva, L.; Bakulina, O.; Dar'in, D.; Krasavin, M. Extending the scope of the new variant of the Castagnoli-Cushman cyclocondensation onto o-methyl benzoic acids bearing various electron-withdrawing groups in the α-position. Molecules 2022, 27, 7211
10. Bannykh, A.; Levashova, E.; Bakulina, O.; Krasavin, M. New Reagent Space and New Scope for the Castagnoli-Cushman Reaction of Oximes. Org. Biomol. Chem. 2022, 20, 8643–8648
11. Krasavin, M.; Peshkov, A. A.; Lukin, A.; Komarova, K.; Vinogradova, L.; Smirnova, D.; Kanov, E. V.; Kuvarzin, S. R.; Murtazina, R. Z.; Efimova, E. V.; Gureev, M.; Onokhin, K.; Zakharov, K.; Gainetdinov, R. R. Discovery and In Vivo Efficacy of Trace Amine-Associated Receptor 1 (TAAR1) Agonist 4-(2-Aminoethyl)-N-(3,5-dimethylphenyl)piperidine-1-carboxamide Hydrochloride (AP163) for the Treatment of Psychotic Disorders. Int. J. Mol. Sci. 2022, 23, 11579
12. Lavit, K.; Sapegin, A.; Linnik, S.; Ryazantsev, M.; Krasavin, M. Steric Push Towards the [n+3] Hydrated Imidazoline Ring Expansion (HIRE) of Dibenzo[1.4]oxazepines and Thiazepines. Eur.J. Org.Chem. 2022, e202200818
13. Sapegin, A.; Rogacheva, E.; Kraeva.; Gureev, M.; Dogonadze, M.; Vinogradova, T.; Yablonsky, P.; Balalaie, S.; Baykov, S. V.; Krasavin, M. Novel 5-Nitrofuran-Tagged Imidazo-Fused Azines and Azoles Amenable by the Groebke-Blackburn-Bienaymé Multicomponent Reaction: Activity Profile against ESKAPE Pathogens and Mycobacteria. Biomedicines 2022, 10, 2203
14. Lukin, A.; Chudinov, M.; Rogacheva, E.; Kraeva, L.; Bakulina, O.; Krasavin, M. Exploration of spirocyclic derivatives of ciprofloxacin as antibacterial agents. Molecules 2022, 27, 4864
15. Barkhatova, D.; Zhukovsky, D.; Heim, D.; Maiwald, S.; Hartmann, M. D.; Krasavin, M. Synthesis of novel glutarimide derivatives via the Ugi multicomponent reaction: affinity towards the E3 ubiquitin ligase substrate receptor Cereblon. Mendeleev Commun. 2022, 32, 747-749
16. Dar'in, D.; Kantin, G.; Bunev, A.; Krasavin, M. Facile and Diastereoselective Arylation of the Privileged 1,4-Dihydroisoquinolin-3(2H)-one Scaffold. Beilstein J. Org. Chem. 2022, 18, 1070-1078
17. Kazantsev, A.; Bakulina, O.; Dar'in, D.; Kantin, G.; Bunev, A.; Krasavin, M. Unexpected Ring Contraction of Homophthalic Anhydrides Under Diazo Transfer Conditions. Org. Lett. 2022, 24, 4762-4765
18. Bakulina, O.; Bannykh, A.; Levashova, E.; Krasavin, M. Conjugates of Iron-Transporting N-Hydroxylactams with Ciprofloxacin. Molecules 2022, 27, 3910
19. Bakulina, O.; Sapegin, A.; Bunev, A.; Krasavin, M. Synthetic Approaches to Constructing Proteolysis Targeting Chimeras (PROTACs). Mendeleev Commun. 2022, 32, 419-432
20. Zhukovsky, D.; Kanov, E.; Gainetdinov, R.; Krasavin, M. Synthesis of a Library of 2-Aryl-2H-tetrazole-5-carboxamides for Photoaffinity Labeling of Aminergic G-Protein Coupled Receptors. Mendeleev Commun. 2022, 32, 604–605
21. Gapanenok, D.; Makhmet, A. Peshkov, A. A.; Smirnova, D.; Amire, N.; Peshkov, V. A.; Spiridonova, D.; Dar'in, D.; Balalaie, S.; Krasavin, M. Multicomponent Assembly of Trisubstituted Imidazoles and Their Photochemical Cyclization into Fused Polyheterocyclic Scaffolds. J. Org. Chem. 2022, 87, 7838-7851
22. Vepreva, A.; Bunev, A. S.; Kudinov, A. Yu.; Kantin, G.; Krasavin, M.; Dar'in, D. Unusual Highly Diastereoselective Rh(II)-catalyzed Dimerization of Diazo Arylidene Succinimides Provides Access to New Dibenzazulene Scaffold. Beilstein J. Org. Chem. 2022, 18, 533–538
23. Krasavin, M.; Jovanović, M.; Podolski-Renić, A.; Pešić, M. The role of the thioredoxin detoxification system in cancer progression and resistance. Front. Mol. Biosci. 2022, 8, 883297
24. Ananeva, A.; Bakulina, O.; Dar'in, D.; Kantin, G.; Krasavin, M. Dicarboxylic Acid Monoesters in β- and δ-Lactam Synthesis. Molecules 2022, 27, 2469
25. Kalinin, S.; Kovalenko, A.; Valtari, A.; Nocentini, A.; Gureev, M.; Urtti, A.; Korsakov, M.; Supuran, C. T.; Krasavin, M. 5-(Sulfamoyl)thien-2-yl 1,3-Oxazole Inhibitors of Carbonic Anhydrase II with Hydrophilic Periphery. J. Enzyme Inhib. Med. Chem. 2022, 37, 1005-1011
26. Krasavin, M.; Shetnev, A.; Panova, V.; Ivanovskyi, S.; Kalinin, S.; Vinogradova, T.; Sharoyko, V.; Yablonsky, P. Hetaryl- and heteroarylvinyl-substituted nitrofurans identified as non-cytotoxic selective antitubercular agents. Mendeleev Commun. 2022, 32, 452-453
27. Zhukovsky, D.; Dar'in, D.; Bakulina, O. Krasavin, M. Preparation and synthetic applications of five-to-seven-membered cyclic α-diazo monocarbonyl compounds. Molecules 2022, 27, 2030
28. Grintsevich, S.; Sapegin, A.; Krasavin, M. Heteroatom is not needed: access to dibenzo[e,h][1,4]diazecin-9-ones from dibenzo[b,e]azepin-6-one via the hydrated imidazoline ring expansion (HIRE) approach. Tetrahedron Lett. 2022, 94, 153718
29. Sharonova, T.; Zhmurov, P.; Kalinin, S.; Nocentini, A.; Angeli, A.; Ferraroni, M.; Korsakov, M.; Supuran, C.; Krasavin, M. Diversely Substituted Sulfamides for Fragment-Based Drug Discovery of Carbonic Anhydrase Inhibitors: Synthesis and Inhibitory Profile. J. Enzyme Inhib. Med. Chem. 2022, 37, 857–865
30. Chupakhin, E. G.; Krasavin, M. Natural compounds as inhibitors of thioredoxin reductase (TrxR1). Russ. Chem. Bull. 2022, 71, 443–448
31. Chupakhin, E. G.; Kantin, G. P.; Dar’in, D. D.; Krasavin, M. Novel chromeno[2,3-c]pyrroles synthesized via intramolecular rhodium(II) carbene trapping. Mendeleev Commun. 2022, 32, 382-383
32. Geyl, K. K.; Baykov, S. V.; Kalinin, S. A.; Bunev, A. S.; Troshina, M. A.; Sharonova, T. V.; Skripkin, M. Y.; Kasatkina, S. O.; Presnukhina, S. I.; Shetnev, A. A.; Krasavin, M. Y.; Boyarskiy, V. P. Synthesis, structure, and antiproliferative action of 2-pyridyl urea-based Cu(II) complexes. Biomedicines 2022, 10, 461
33. Guranova, N.; Bakulina, O.; Dar'in D.; Kantin, G.; Krasavin, M. Homophthalic Esters: A New Type of Reagents for the Castagnoli-Cushman Reaction. Eur. J. Org. Chem. 2022, e202101281
34. Paramonova, P.; Bakulina, O.; Nabiyev, A.; Dar'in, D.; Krasavin, M. The Castagnoli-Cushman reaction of 3-aryl glutaric acids: a convenient, diastereoselective entry into medicinally important 6-oxo-2,4-diarylpiperidine-3-carboxylic acid scaffold. ChemistrySelect 2022, 7, e202104011
35. Zhukov, A. S.; Khairutdinov, V. R.; Samtsov, A. V.; Krasavin, M.; Garabadzhiu, A. V. Preclinical Efficacy Investigation of Human Neutrophil Elastase Inhibitor Sivelestat in Animal Model of Psoriasis. Skin Health Dis. 2022, 2, e90
36. Grintsevich, S.; Sapegin, A.; Krasavin, M. Significant Broadening of the Substrate Scope for the Hydrated Imidazoline Ring Expansion (HIRE) via the Use of Lithium Hexamethyldisylazide. Synthesis 2022, 54, 2494-2510
37. Vepreva, A.; Kantin, G.; Krasavin, M.; Dar'in. A General Way to Spiro-Annulated 2-Benzoxepines via Rh₂(esp)₂-catalyzed [5+2] Cycloaddition of Diazo Arylidene Succinimides to Ketones. Synthesis 2022, 54, 5128-5138
38. Peshkov, A. A.; Makhmet, A.; Bakulina, O.; Kanov, E.; Gainetdinov, R.; Peshkov, V. A.; Dar'in, D.; Krasavin, M. A general approach to spirocyclic piperidines via Castagnoli-Cushman chemistry. Synthesis 2022, 54, 2604-2615
39. Paramonova, P.; Sharonova, S.; Kalinin, S.; Chupakhin, E.; Bunev, A.; Krasavin, M. (E)-3-Arylidene-4-diazopyrrolidine-2,5-diones conveniently elaborated into cytotoxic compounds bearing a primary sulfonamide and a Michael acceptor moieties. Mendeleev Commun. 2022, 32, 176-177
40. Krasavin, M.; Bubyrev, A.; Kazantsev, A.; Heim, C.; Maiwald,S.; Zhukovsky, D.; Dar'in, D.; Hartmann, M. D.; Bunev, A. Replacing the Phthalimide Core in Thalidomide with Benzotriazole. J. Enzyme Inhib. Med. Chem. 2022, 37, 527-530
41. Kazantsev, A.; Krasavin, M. Ligands for Cereblon: 2017–2021 Patent Overview. Exp. Opin. Ther. Pat. 2022, 32, 171-190
42. Grintsevich, S.; Sapegin, A.; Duszyńska, B.; Bojarski, A. J.; Krasavin, M. An attempt at the hydrated imidazoline ring expansion (HIRE) of diarene-fused [1,4]diazepinones delivers selective dopamine D₂ receptor ligands. Synthesis 2022, 54, 658-666
43. Firsov, A.; Bakulina, O.; Dar´in, D.; Sokolov, V.; Krasavin, M. Synthesis of γ-sultam-annelated δ-lactams via the Castagnoli-Cushman reaction of sultam-based dicarboxylic acids. J. Org. Chem. 2022, 87, 1537-1540

2021

1. Kalinin, S.; Malkova, A.; Sharonova, T.; Sharoyko, V.; Bunev, A.; Supuran, C. T.; Krasavin, M. Carbonic anhydrase IX inhibitors as candidates for combination therapy of solid tumors. Int. J. Mol. Sci. 2021, 22, 13405
2. Budeev, A.; Kantin, G.; Dar'in, D.; Krasavin, M. Ugi reaction-derived 1H-pyrrol-2(5H)-ones proved as valid precursors to a new class of heterocyclic α-diazocarbonyl compounds. Tetrahedron Lett. 2021, 89, 153598
3. Levashova, E.; Bakulina, O.; Dar'in, D.; Krasavin, M. Catalyst-Free Synthesis of Diastereomerically Pure 3-Cyanoazetidin-2-ones via Thermally Promoted Tandem Wolff Rearrangement–Staudinger [2+2] Cycloaddition. ChemistrySelect 2021, 6, 13582-13588
4. Bubyrev, A.; Malkova, K.; Kantin, G.; Dar´in, D.; Krasavin, M. Metal-free synthesis of 1,5-disubstituted 1,2,3-triazoles. J. Org. Chem. 2021, 86, 17516-17522
5. Krasavin, M.; Dar'in, D.; Balalaie, S. Post-condensational modifications of the Groebke‐Blackburn‐Bienaymé reaction products for scaffold-oriented synthesis. Tetrahedron Lett. 2021, 86, 153521
6. Bakulina, O.; Inyutina, A.; Dar'in, D.; Krasavin, M. Multicomponent Reactions Involving Diazo Reagents: A 5-Year Update. Molecules 2021, 26, 6563
7. Chupakhin, E.; Bakulina, O.; Dar'in, D.; Krasavin, M. Facile entry into the 1H-pyrrolo[3,4-b]indolizine-1,3(2H)-dione scaffold via intramolecular Rh(II) carbene trapping. Tetrahedron Lett. 2021, 85, 153467
8. Nayebzadeh, B.; Amiri, K.; Khosravi, H.; Mirzaei, S.; Rominger, F.; Dar’in, D.; Krasavin, M.; Bijanzadeh, H. R.; Balalaie, S. Synthesis of Spiro[chromene-imidazo[1,2-a]pyridin]-3'-imines via 6-exo-dig Cyclization Reaction. J. Org. Chem. 2021, 86, 13693-13701
9. Inyutina, A.; Kantin, G.; Dar´in, D.; Krasavin, M. Diastereoselective Formal [5+2] Cycloaddition of Diazo Arylidene Succinimides-Derived Rhodium Carbenes and Aldehydes: A Route to 2-Benzoxepines. J. Org. Chem. 2021, 86, 13673-13683
10. Bubyrev, A.; Adamchik, M.; Dar´in, D.; Kantin, G.; Krasavin, M. Metal-Free Three-Component Synthesis of 1,2,3-Triazoline-4-Sulfonamides. J. Org. Chem. 2021, 86, 13454-13464
11. Safrygin, A.; Zhmurov, P.; Dar'in, D.; Silonov, S.; Kasatkina, M.; Zonis, Y.; Gureev, M.; Krasavin, M. 1-Oxo-3,4-dihydroisoquinoline-4-carboxamides as novel druglike inhibitors of poly(ADP-ribose) polymerase (PARP) with favorable ADME characteristics. J. Enzyme Inhib. Med. Chem. 2021, 36, 1968-1983
12. Safrygin, A.; Zhmurov, P.; Dar'in, D.; Silonov, S.; Kasatkina, M.; Zonis, Y.; Gureev, M.; Krasavin, M. Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP). J. Enzyme Inhib. Med. Chem. 2021, 36, 1916-1921
13. Pilipenko, I.; Korzhikov-Vlakh, V.; Valtari, A.; Anufrikov, Y.; Kalinin, S.; Ruponen, M.; Krasavin, M.; Urtti, A.; Tennikova, T. Mucoadhesive properties of nanogels based on stimuli-sensitive glycosaminoglycan-graft-pNIPAAm copolymers. Int. J. Biol. Macromol. 2021, 186, 8644-872
14. Solovyev, I.; Dar'in, D.; Krasavin, M. Novel 3,4-dihydro-1,4-oxazine (dehydromorpholine) sulfonamides and sulfones conveniently accessed from suitable alpha-diazoketones via O—H carbene insertion – Cyclization sequence. Tetrahedron Lett. 2021, 78, 153269
15. Lukin, A.; Bakholdina, A.; Chudinov, M.; Onopchenko, O.; Zhuravel, E.; Zozulya, S.; Gureev, M.; Krasavin, M. Strained contacts with the cell membrane may influence ligand affinity to G protein coupled receptors: a case of free fatty acid receptor 1 agonists. J. Enzyme Inhib. Med. Chem. 2021, 36, 1651-1658
16. Krasavin, M.; Zhukovsky, D.; Solovyev, I.; Barkhatova, D.; Dar’in, I.; Frank, D.; Martinelli, G.; Weizel, L.; Proschak, A.; Rotter, M.; Kramer, J. S.; Brunst, S.; Wichelhaus, T. A.; Proschak, E.* Rh^II-Catalyzed De-symmetrization of Ethane-1,2-dithiol and Propane-1,3-dithiol Yields Metallo-β-lactamase Inhibitors, ChemMedChem 2021, 16, 3410-3417. Nominated VERY IMPORTANT PAPER.
17. Guranova, N.; Dar'in, D.; Kantin, G.; Krasavin, M. Oxonium ylides generated from 1,4-disubstituted α-diazo glutaconimides: a rich source of diverse oxygen heterocyclic frameworks. Eur. J. Org. Chem. 2021, 3411-3420
18. Dar'in, D.; Kantin, G.; Kalinin, S.; Sharonova, T.; Bunev, A.; Ostapenko, G. I.; Nocentini, A.; Sharoyko, V.; Supuran, C. T.; Krasavin, M. Investigation of 3-sulfamoyl coumarins against cancer-related IX and XII isoforms of human carbonic anhydrase as well as cancer cells leads to the discovery of 2-oxo-2H-benzo[h]chromene-3-sulfonamide – a new caspase-activating proapoptotic agent. Eur. J. Med. Chem. 2021, 222, 113589
19. Inyutina, A.; Dar'in, D.; Kantin, G.; Krasavin, M. Tricyclic 2-Benzazepines Obtained via an Unexpected Cyclization Involving Nitrilium Ylides. Org. Biomol. Chem. 2021, 19, 5068-5071
20. Supuran, C. T.; Nocentini, A.; Yakubova, E.; Savchuk, N.; Kalinin, S.; Krasavin, M. Biochemical profiling of anti-HIV prodrug Elsulfavirine (Elpida®) and its active form VM1500A against a panel of twelve human carbonic anhydrase isoforms. J. Enzyme Inhib. Med. Chem. 2021, 36, 1056-1060
21. Budeev, A.; Kantin, G.; Dar'in, D.; Krasavin, M. Diazocarbonyl and Related Compounds in the Synthesis of Azoles. Molecules 2021, 26, 2530
22. Dar'in, D.; Kantin, G.; Chupakhin, E.; Sharoyko, V.; Krasavin, M. Natural-like Spirocyclic Δ^α,β-Butenolides Obtained from Diazo Homophthalimides. Chem. Eur. J. 2021, 27, 8221-8227
23. Sapegin, A. V.; Peshkov, A. A.; Kanov, E. V.; Gainetdinov, R. R.; Duszyńska, B.; Bojarski, A. J.; Krasavin, M. Novel medium-sized di(het)areno-fused 1,4,7-(oxa)thiadiazecines as probes for aminergic receptors. Mendeleev Commun. 2021, 31, 501-503
24. Guranova, N.; Golubev, P.; Bakulina, O.; Dar'in, D.; Kantin, G.; Krasavin, M. Unexpected formal [4+2]-cycloaddition of chalcone imines and homophthalic anhydrides: preparation of dihydropyridin-2(1H)-ones. Org. Biomol. Chem. 2021, 19, 3829-3833
25. Levashova, E.; Firsov, A.; Bakulina, O.; Peshkov, A.; Kanov, E.; Gainetdinov, R. R.; Krasavin, M. Rare cis-configured 2,4-disubstituted-1-alkylpiperidines synthesized and tested against trace-amine-associated receptor 1 (TAAR1). Mendeleev Commun. 2021, 31, 488-489
26. Reutskaya, E.; Sapegin, A.; Peintner, S.; Erdélyi, M.; Krasavin, M. Sulfur Oxidation Increases the Rate of HIRE-type [1.4]Thiazepinone Ring Expansion and Influences the Conformation of a Medium-Sized Heterocyclic Scaffold. J. Org. Chem. 2021, 86, 5778-5791
27. Chupakhin, E.; Krasavin, M. Thioredoxin reductase inhibitors: updated patent review (2017-present). Exp. Opin. Ther. Pat. 2021, 31, 745-758
28. Kazantsev, A.; Zhukovsky, D.; Bubyrev, A.; Dar'in, D.; Krasavin, M. Fluorination of α-diazo-γ-lactams with the Olah reagent. Tetrahedron Lett. 2021, 69, 152969
29. Sharonova, T.; Paramonova, P.; Kalinin, S.; Bunev, A.; Gasanov, R. E.; Nocentini, A.; Sharoyko, V.; Tennikova, T. B.; Dar'in, D.; Supuran, C. T.; Krasavin, M. Insertion of Metal Carbenes Into the Anilinic N–H Bond of Unprotected Aminobenzenesulfonamides Delivers Low Nanomolar Inhibitors of Human Carbonic Anhydrase IX and XII isoforms. Eur. J. Med. Chem. 2021, 218, 113352
30. Kalinin, S.; Vedekhina, T.; Paramonova, P.; Krasavin, M. Antimicrobial activity of 5-membered nitroheteroaromatic compounds beyond nitrofurans and nitroimidazoles: recent progress. Curr. Med. Chem. 2021, 28, 5926-5982
31. Peshkov, A. A.; Bakulina, O.; Dar'in, D.; Kantin, G.; Bannykh, A.; Peshkov, V. A.; Krasavin, M. Three-component Castagnoli-Cushman reaction of 3-arylglutaconic acid anhydrides, carbonyl compounds and ammonium acetate: a quick and flexible way to assemble polysubstituted NH-δ-lactams. Eur. J. Org. Chem. 2021, 1726–1731. COVER FEATURE
32. Klochkova, A.; Bubyrev, A.; Dar'in, D. Bakulina, O.*; Krasavin, M.; Sokolov, V. Straightforward Route to γ-Sultams via Novel Tandem S_N/Michael Addition. Synthesis 2021, 53, 1795-1804
33. Budeev, A. V.; Kantin, G. P.; Dar'in, D.; Krasavin, M. Continued exploration of trifunctional alkyl 4-chloro-2-diazo-3-oxobutanoates: streamlined entry into [1,2,3]triazolo[5,1-c][1,4]benzoxazines and [1,2,3]triazolo[5,1-c][1,4]benzoxazepines. Synthesis 2021, 53, 2155-2166
34. Chupakhin, E. G.; Kantin, G. P.; Dar'in, D. V.; Krasavin, M. Convenient preparation of (E)-3-arylidene-4-diazopyrrolidine-2,5-diones in array format. Mendeleev Commun. 2021, 31, 36-38
35. Chupakhin, E.; Gecht, M.; Ivanov, A.; Kantin, G.; Dar'in, D.; Krasavin, M. (E)-3-Arylidene-4-diazopyrrolidine-2,5-diones: preparation and use in Rh^II-catalyzed X–H insertion reactions towards novel, medicinally important Michael acceptors. Synthesis 2021, 53, 1292-1300
36. Solovyev, I.; Eremeyeva, M.; Zhukovsky, D.; Dar'in, D.; Krasavin, M. Cyclic diazo compounds in the construction of spirocyclic scaffolds. Tetrahedron Lett. 2021, 62, 152671
37. Burianova, V.; Kalinin, S.; Krasavin, M.; Supuran, C. T. Radiotracers for positron emission tomography (PET) targeting tumour-associated carbonic anhydrase isoforms. Eur. J. Med. Chem. 2021, 213, 113046
38. Bubyrev, A.; Kantin, G.; Dar'in, D.; Krasavin, M. CH-Diazomethane sulfonamides generated in situ for intramolecular [3+2] cycloaddition of alkynes: an entry into novel pyrazole-fused five-membered sultams. Synthesis 2021, 53, 1434-1442 (Featured Article)
39. Hiesinger, K.; Dar'in, D.; Proschak, E.; Krasavin, M. Spirocyclic Scaffolds in Medicinal Chemistry. J. Med. Chem. 2021, 64, 150–183
40. Guranova, N.; Kantin, G.; Dar'in, D.; Krasavin, M. Diazo glutaconimides: an unexplored type of heterocyclic α-diazocarbonyl compounds conveniently evolved into pyridine-2,6(1H,3H)-diones and oxazolo[5,4-b]pyridin-5(4H)-ones. Eur. J. Org. Chem. 2021, 623-631
41. Lukin, A.; Bakholdina, A.; Zhurilo, N.; Onopchenko, O.; Zhuravel, E.; Zozulya, S.; Gureev, M.; Safrygin, A.; Krasavin, M. Exploration of nitrogen heterocyclic periphery around the core of advanced FFA1 agonist fasiglifam (TAK-875). Arch. Pharm. 2021, 354, 2000275