Synthesis and Characterization of Dihydrouracil Analogs Utilizing Biginelli Hybrids
Abstract
:1. Introduction
2. Results and Discussion
3. Materials and Methods
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Krokan, H.E.; Drabløs, F.; Slupphaug, G. Uracil in DNA–occurrence, consequences and repair. Oncogene 2002, 21, 8935–8948. [Google Scholar] [CrossRef] [Green Version]
- Inada, M.; Hirao, Y.; Koga, T.; Itose, M.; Kunizaki, J.-i.; Shimizu, T.; Sato, H. Relationships among plasma [2-13C] uracil concentrations, breath 13CO2 expiration, and dihydropyrimidine dehydrogenase (DPD) activity in the liver in normal and DPD-deficient dogs. Drug Metab. Disp. 2005, 33, 381–387. [Google Scholar] [CrossRef] [Green Version]
- Hollywood, F.; Suschitzky, H.; Hull, R. Chlorosulphonyl isocyanate addition to o-dialkylaminostyrenes: Preparation of 6-(O-dialkylaminophenyl)-uracils. Synthesis 1982, 8, 662–665. [Google Scholar] [CrossRef]
- Strekowski, L.; Watson, R.A.; Michelle, F.A. A new route to 5, 6-dihydropyrimidin-4 (3H)-ones. Synthesis 1987, 6, 579–581. [Google Scholar] [CrossRef]
- Pair, E.; Levacher, V.; Briere, J.-F. Modified multicomponent Biginelli–Atwal reaction towards a straightforward construction of 5,6-dihydropyrimidin-4-ones. RSC Adv. 2015, 57, 46267–46271. [Google Scholar] [CrossRef]
- Schneider, N.; Hauer, B.; Ditrich, K.; O’Neil, M.; Turner, N. Preparation of Beta-Amino Acids. Patent WO 2011032990 A1, 24 March 2011. [Google Scholar]
- O’Neill, M.; Hauer, B.; Schneider, N.; Turner, N.J. Enzyme-catalyzed enantioselective hydrolysis of dihydrouracils as a route to enantiomerically pure β-Amino Acids. ACS Catal. 2011, 9, 1014–1016. [Google Scholar] [CrossRef]
- Jones, K.A.; Weaver, D.F.; Tiedje, K.E. Dihydrouracil Compounds as Anti-Ictogenic or Anti-Epileptogenic Agents. Patent WO 2004009559 A2, 29 January 2004. [Google Scholar]
- Sun, G.; Fecko, C.J.; Nicewonger, R.B.; Webb, W.W.; Begley, T.P. DNA-protein cross-linking: Model systems for pyrimidine-aromatic amino acid cross-linking. Org. Lett. 2006, 8, 681–683. [Google Scholar] [CrossRef]
- Wu, S.; Janusz, J.M. Solid-phase synthesis of 3-aminohydantoin, dihydrouracil, thiohydantoin and dihydrothiouracil derivatives. Tetrahedron Lett. 2000, 41, 1165–1169. [Google Scholar]
- Blanco-Ania, D.; Valderas-Cortina, C.; Hermkens, P.H.H.; Sliedregt, L.A.J.M.; Scheeren, H.W.; Rutjes, F.P.J.T. Synthesis of dihydrouracils spiro-fused to pyrrolidines: Druglike molecules based on the 2-arylethyl amine scaffold. Molecules 2010, 15, 2269–2301. [Google Scholar] [CrossRef] [Green Version]
- Chang, K.L.; Jeung, Y.S. A Synthesis of 5,6-Dihydrouracils in a Sealed-tube and Their Conformational Analysis. Bull. Korean Chem. Soc. 1991, 12, 343–347. [Google Scholar]
- Wurm, J.P.; Griese, M.; Bahr, U.; Held, M.; Heckel, A.; Karas, M.; Soppa, J.; Wöhnert, J. Identification of the enzyme responsible for N1-methylation of pseudouridine 54 in archaeal tRNAs. RNA 2012, 18, 412–420. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Svitkin, Y.V.; Cheng, Y.M.; Chakraborty, T.; Presnyak, V.; John, M.; Sonenberg, N. N1-methyl-pseudouridine in mRNA enhances translation through eIF2α-dependent and independent mechanisms by increasing ribosome density. Nucleic Acids Res. 2017, 45, 6023–6036. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morais, P.; Adachi, H.; Yu, Y.-T. The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines. Front. Cell Dev. Biol. 2021, 9, 789427. [Google Scholar] [CrossRef]
- Richner, J.M.; Himansu, S.; Dowd, K.A.; Butler, S.L.; Salazar, V.; Fox, J.M.; Julander, J.G.; Tang, W.W.; Shresta, S.; Pierson, T.C.; et al. Modified mRNA vaccines protect against Zika virus infection. Cell 2017, 168, 1114–1125. [Google Scholar] [CrossRef] [Green Version]
- Pardi, N.; Hogan, M.J.; Naradikian, M.S.; Parkhouse, K.; Cain, D.W.; Jones, L.; Moody, M.A.; Verkerke, H.P.; Myles, A.; Willis, E.; et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J. Exp. Med. 2018, 215, 1571–1588. [Google Scholar] [CrossRef]
- Meyer, M.; Huang, E.; Yuzhakov, O.; Ramanathan, P.; Ciaramella, G.; Bukreyev, A. Modified mRNA-based vaccines elicit robust immune responses and protect guinea pigs from Ebola virus disease. J. Infect. Dis. 2018, 217, 451–455. [Google Scholar] [CrossRef]
- Das, D. Chapter 8—Design and Development of HCV NS5B Polymerase Inhibitors. In Viral Proteases and Their Inhibitors; Academic Press: Cambridge, MA, USA, 2017; pp. 189–219. [Google Scholar]
- Malik, V.; Singh, P.; Kumar, S. Unique chlorine effect in regioselective one-pot synthesis of 1-alkyl-/allyl-3-(o-chlorobenzyl) uracils: Anti-HIV activity of selected uracil derivatives. Tetrahedron 2006, 62, 5944–5951. [Google Scholar] [CrossRef]
- Maruyama, T.; Kozai, S.; Demizu, Y.; Witvrouw, M.; Pannecouque, C.; Balzarini, J.; Snoecks, R.; Andrei, G.; De Clercq, E. Synthesis and anti-HIV-1 and anti-HCMV activity of 1-substituted 3-(3,5-dimethylbenzyl) uracil derivatives. Chem. Pharm. Bull. 2006, 54, 325–333. [Google Scholar] [CrossRef] [Green Version]
- Barral, K.; Courcambeck, J.; Pepe, G.; Balzarini, J.; Neyts, J.; Clercq, E.D.; Camplo, M. Synthesis and Antiviral Evaluation of Cis-Substituted Cyclohexenyl and Cyclohexanyl Nucleosides. J. Med. Chem. 2005, 48, 450–456. [Google Scholar] [CrossRef]
- Dolman, N.P.; Troop, H.M.; More, J.C.A.; Alt, A.; Knauss, J.L.; Nistico, R.; Jack, S.; Morley, R.M.; Bortolotto, Z.A.; Roberts, P.J.; et al. Synthesis and pharmacology of willardiine derivatives acting as antagonists of kainate receptors. Med. Chem. 2005, 48, 7867–7881. [Google Scholar] [CrossRef]
- Mai, A.; Sbardella, G.; Artico, M.; Ragno, R.; Massa, S.; Novellino, E.; Greco, G.; Lavecchia, A.; Musiu, C.; Colla, M.L.; et al. Structure-Based Design, Synthesis, and Biological Evaluation of Conformationally Restricted Novel 2-Alkylthio-6-[1-(2,6-difluorophenyl)alkyl]- 3,4-dihydro-5-alkylpyrimidin-4(3H)-ones as Non-nucleoside Inhibitors of HIV-1 Reverse Transcriptase. J. Med. Chem. 2001, 44, 2544–2554. [Google Scholar] [CrossRef] [PubMed]
- Heidelberger, C.; Chaudhuri, N.K.; Danneberg, P.; Mooren, D.; Griesbach, L.; Duschinsky, R.; Schnitzer, R.J.; Pleven, E.; Scheiner, J. Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature 1957, 179, 663–666. [Google Scholar] [CrossRef] [PubMed]
- Udayakumar, V.; Gowiska, J.; Pandurangan, A.J. A novel synthesis and preliminary in vitro cytotoxic evaluation of dihydropyrimidine-2,4(1H,3H)-dione derivatives. J. Chem. Sci. 2017, 129, 249–258. [Google Scholar] [CrossRef] [Green Version]
- Embrey, M.W.; Wai, J.S.; Funk, T.W.; Homnick, C.F.; Perlow, D.S.; Young, S.D.; Vacca, J.P.; Hazuda, J.D.; Felock, P.J.; Stillmock, K.A.; et al. A series of 5-(5,6)-dihydrouracil substituted 8-hydroxy-[1,6] naphthyridine-7-carboxylic acid 4-fluorobenzylamide inhibitors of HIV-1 integrase and viral replication in cells. Bioorg. Med. Chem. Lett. 2005, 15, 4550–4554. [Google Scholar] [CrossRef]
- Sganappa, A.; Bellucci, M.C.; Nizet, V.; Tor, Y.; Volonterio, A. Multicomponent Domino Synthesis and Antibacterial Activity of Neomycin–Sugar Conjugates. Synthesis 2016, 48, 4443–4445. [Google Scholar]
- Aytemir, M.D.; Çalış, U.; Özalp, M. Synthesis of Some New 3-Ethyl-6-phenylhexahydropyrimidine-2,4-dione Derivatives and Evaluation of Their In vitro Antimicrobial Activities. Hacet. Univ. J. Fac. Pharm. 2002, 22, 9–18. [Google Scholar]
- Heravi, M.M.; Moradi, R.; Mohammadkhani, L.; Moradi, B. Current progress in asymmetric Biginelli reaction: An update. Mol. Divers. 2018, 22, 751–767. [Google Scholar] [CrossRef]
- Chopda, L.V.; Dave, P.N. Recent Advances in Homogeneous and Heterogeneous Catalyst in Biginelli Reaction from 2015-19: A Concise Review. Chem. Sel. 2020, 5, 5552–5572. [Google Scholar] [CrossRef]
- Qin, H.-L.; Shang, Z.-P.; Jantan, I.; Tan, Q.A.; Hussain, M.A.; Sherd, M.; Bukhari, S.N.A. Molecular docking studies and biological evaluation of chalcone based pyrazolines as tyrosinase inhibitors and potential anticancer agents. RSC Adv. 2015, 5, 46330–46338. [Google Scholar] [CrossRef]
- Bukhari, S.N.A.; Zhang, X.; Jantan, I.; Zhu, H.-L.; Amjad, M.W.; Masand, V.H. Synthesis, molecular modeling, and biological evaluation of novel 1,3-diphenyl-2-propen-1-one based pyrazolines as anti-inflammatory agents. Chem. Biol. Drug Des. 2015, 85, 729–742. [Google Scholar] [CrossRef]
- Abdelrahman, M.H.; Youssif, B.G.M.; Abdelgawad, M.A.; Abdelazeem, A.H.; Ibrahim, H.M.; Moustafa, A.G.A.; Treamblu, L.; Bukhari, S.N.A. Synthesis, biological evaluation, docking study and ulcerogenicity profiling of some novel quinoline-2-carboxamides as dual COXs/LOX inhibitors endowed with anti-inflammatory activity. Eur. J. Med. Chem. 2017, 127, 972–985. [Google Scholar] [CrossRef] [PubMed]
- Bukhari, S.N.A.; Butt, A.M.; Amjad, M.V.B.; Ahmad, W.; Shah, W.H.; Trivedi, A.R. Synthesis and evaluation of chalcone analogues based pyrimidines as angiotensin converting enzyme inhibitors. Pak. J. Biol. Sci. 2013, 16, 1368–1372. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Milović, E.; Petronijević, J.; Joksimović, N.; Beljkaš, M.; Ružić, D.; Nikolić, K.; Vraneš, M.; Tot, A.; Đorđić Crnogorac, M.; Stanojković, T.; et al. Anticancer evaluation of the selected tetrahydropyrimidines: 3D-QSAR, cytotoxic activities, mechanism of action, DNA, and BSA interactions. Mol. Struct. 2022, 1257, 132621. [Google Scholar] [CrossRef]
- Janković, N.; Trifunović, J.; Vraneš, M.; Tot, A.; Petronijević, J.; Joksimović, N.; Stanojković, T.; Đorđić Crnogorac, M.; Petrović, N.; Boljević, I.; et al. Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels. Bioorg. Chem. 2019, 86, 569–582. [Google Scholar] [CrossRef] [PubMed]
- Muškinja, J.; Janković, N.; Ratković, Z.; Bogdanović, G.; Bugarčić, Z. Vanillic aldehydes for the one-pot synthesis of novel 2-oxo-1,2,3,4-tetrahydropyrimidines. Mol. Divers. 2016, 20, 591–604. [Google Scholar] [CrossRef] [PubMed]
- Gavrilović, M.; Janković, N.; Joksović, L.J.; Petronijević, J.; Joksimović, N. Bugarčić, Z. Water ultrasound-assisted oxidation of 2-oxo-1,2,3,4-tetrahydropyrimidines and benzylic acid salts. Environ. Chem. Lett. 2018, 16, 1501–1506. [Google Scholar] [CrossRef]
- Milović, E.; Janković, N.; Bogdanović, G.; Petronijević, J.; Joksimović, N. On water synthesis of the novel 2-oxo-1,2,3,4-tetrahydropyrimidines. Tetrahedron 2021, 78, 131790. [Google Scholar] [CrossRef]
- Janković, N.; Stefanović, S.; Petronijević, J.; Joksimović, N.; Novaković, S.B.; Bogdanović, G.A.; Muškinja, J.; Vraneš, M.; Ratković, Z.; Bugarčić, Z. Water-Tuned Tautomer-Selective Tandem Synthesis of the 5,6-Dihydropyrimidin-4(3H)-ones, Driven under the Umbrella of Sustainable Chemistry. ACS Sustain. Chem. Eng. 2018, 6, 13358–13366. [Google Scholar] [CrossRef]
- Mayer, U.; Gutmann, V.; Gerger, W. The acceptor number—A quantitative empirical parameter for the electrophilic properties of solvents. Mon. Chem. 1975, 106, 1235–1257. [Google Scholar] [CrossRef]
- Hayamizu, K.; Aihara, Y.; Arai, S.; Martinez, C.G. Pulse-Gradient Spin-Echo 1H, 7Li, and 19F NMR Diffusion and Ionic Conductivity Measurements of 14 Organic Electrolytes Containing LiN(SO2CF3)2. J. Phys. Chem. B 1999, 103, 519–524. [Google Scholar] [CrossRef]
- Kamlet, M.J.; Taft, R.W. The solvatochromic comparison method. I. The .beta.-scale of solvent hydrogen-bond acceptor (HBA) basicities. J. Am. Chem. Soc. 1976, 98, 377–383. [Google Scholar] [CrossRef]
- Kamlet, M.J.; Abboud, J.-L.M.; Abraham, M.H.; Taft, R.W. Linear solvation energy relationships. 23. A comprehensive collection of the solvatochromic parameters,. pi.*,. alpha., and. beta., and some methods for simplifying the generalized solvatochromic equation. J. Org. Chem. 1983, 48, 2877–2887. [Google Scholar] [CrossRef]
- Singh, S.; Schober, A.; Gebinog, M.; Groß, A. Facile conversion of Biginelli 3, 4-dihydropyrimidin-2(1H)-thiones to 2-(2-hydroxy-2-arylvinyl) dihydropyrimidines via Eschenmoser coupling. Tetrahedron Lett. 2009, 50, 1838–1843. [Google Scholar] [CrossRef]
Entry | Conditions | Yields of 2a (%) |
---|---|---|
1 | mCPBA/toluene | 51 |
2 | mCPBA/dioxane | 32 |
3 | mCPBA/water | - |
4 | mCPBA/CHCl3 | 40 |
5 | mCPBA/DCM | 75 |
6 | mCPBA/THF a | 29 |
Solvent | Solvent Parameter | ||
---|---|---|---|
ε | HBA | π* | |
Toluene | 2.4 | - | 0.54 |
DCM | 9.1 | - | 0.82 |
CHCl3 | 4.8 | - | 0.58 |
Dioxane | 2.3 | 0.37 | 0.55 |
Water | 80 | 0.18 | 1.09 |
THF | 7.6 | 0.55 | 0.58 |
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Bukhari, S.N.A.; Ejaz, H.; Elsherif, M.A.; Janković, N. Synthesis and Characterization of Dihydrouracil Analogs Utilizing Biginelli Hybrids. Molecules 2022, 27, 2939. https://doi.org/10.3390/molecules27092939
Bukhari SNA, Ejaz H, Elsherif MA, Janković N. Synthesis and Characterization of Dihydrouracil Analogs Utilizing Biginelli Hybrids. Molecules. 2022; 27(9):2939. https://doi.org/10.3390/molecules27092939
Chicago/Turabian StyleBukhari, Syed Nasir Abbas, Hasan Ejaz, Mervat A. Elsherif, and Nenad Janković. 2022. "Synthesis and Characterization of Dihydrouracil Analogs Utilizing Biginelli Hybrids" Molecules 27, no. 9: 2939. https://doi.org/10.3390/molecules27092939