Abstract
Background: This paper aims to reveal an urgent industrial scheme for a fast and facile total synthesis of umifenovir (arbidol) (by one-pot stages) as an antiviral agent for treating the 2019-nCoV virus via inhibiting its viral replication in the human cells. As COVID-19 takes thousands of lives all around the world, it seems that the medicinal resources would not be enough to supply billions of peoples currently living on the planet. Thus, this pandemic and its subsequent impacts on the natural order of our life would be one of the most important threats against the entire human race.
Methods: In this project, we have made attempts to find an operative approach for synthesizing this compound as an active pharmaceutical ingredient (API), which showed it could be effective in inhibiting the newly emerged coronavirus..
Results: The designed scheme uses relatively cheap precursors and contains one pot stage instead of seven time-consuming and more costly linear steps. Moreover, safe and cheap solvents have been used like water and ethanol, instead of toxic ones like methanol and pyridine which could cause rejection of the API in the organic volatile impurities (OVI) test of pharmacopeia analysis, as well as increase the concern of inflammability, explosivity, and carcinogenic properties of those common solvents.
Conclusion: The most important pharmaceutical analytical methods containing OVI test (mainly ethanol (about 171 ppm) much lower than the limits, by gas chromatography-Flame Ionization Detector (GC-FID) instrument), assay content (about 99.6% by potentiometric titration), and related purity analysis (by high-performance liquid chromatography-Ultraviolet Detector (HPLCUV)) (about 99.8%) were performed and described to give a more clear industrial scheme.
Keywords: Umifenovir, total synthesis, COVID-19 antiviral, GC-FID, HPLC, potentiometric titration.
Graphical Abstract
[1]
Ormsby, C.E.; Reyes-Terán, G. Influenza: making privileged data public. Science, 2009, 325(5944), 1072-1072.
[http://dx.doi.org/10.1126/science.325_1072a] [PMID: 19713511]
[http://dx.doi.org/10.1126/science.325_1072a] [PMID: 19713511]
[2]
Zink, A.R.; Reischl, U.; Wolf, H.; Nerlich, A.G. Molecular analysis of ancient microbial infections. FEMS Microbiol. Lett., 2002, 213(2), 141-147.
[http://dx.doi.org/10.1111/j.1574-6968.2002.tb11298.x] [PMID: 12167530]
[http://dx.doi.org/10.1111/j.1574-6968.2002.tb11298.x] [PMID: 12167530]
[3]
(a) Zhang, L.; Lin, D.; Sun, X.; Curth, U.; Drosten, C.; Sauerhering, L.; Becker, S.; Rox, K.; Hilgenfeld, R. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors. Science, 2020, 368(6489), 409-412.
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
(b) Alexpandi, R.; De Mesquita, J.F.; Pandian, S.K.; Ravi, A.V. Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: An in silico Analysis. Front. Microbiol., 2020, 11, 1796.
[http://dx.doi.org/10.3389/fmicb.2020.01796] [PMID: 32793181]
(c) Ferraz, W.R.; Gomes, R.A.; S Novaes, A.L.; Goulart Trossini, G.H. Ligand and structure-based virtual screening applied to the SARS-CoV-2 main protease: an in silico repurposing study. Future Med. Chem., 2020, 12(20), 1815-1828.
[http://dx.doi.org/10.4155/fmc-2020-0165] [PMID: 32787684]
[http://dx.doi.org/10.1126/science.abb3405] [PMID: 32198291]
(b) Alexpandi, R.; De Mesquita, J.F.; Pandian, S.K.; Ravi, A.V. Quinolines-Based SARS-CoV-2 3CLpro and RdRp Inhibitors and Spike-RBD-ACE2 Inhibitor for Drug-Repurposing Against COVID-19: An in silico Analysis. Front. Microbiol., 2020, 11, 1796.
[http://dx.doi.org/10.3389/fmicb.2020.01796] [PMID: 32793181]
(c) Ferraz, W.R.; Gomes, R.A.; S Novaes, A.L.; Goulart Trossini, G.H. Ligand and structure-based virtual screening applied to the SARS-CoV-2 main protease: an in silico repurposing study. Future Med. Chem., 2020, 12(20), 1815-1828.
[http://dx.doi.org/10.4155/fmc-2020-0165] [PMID: 32787684]
[4]
(a) Shahinshavali, S.; Hossain, K. A.; Kumar, A. V. D. N.; Reddy, A. G.; Kolli, D.; Nakhi, A.; Pal, M. Ultrasound assisted synthesis of 3-alkynyl substituted 2-chloroquinoxaline derivatives: Their in silico assessment as potential ligands for N-protein of SARS-CoV-2. Tetrahedron let., 2020, 61, 152336.
(b) Hagar, M.; Ahmed, H.A.; Aljohani, G.; Alhaddad, O.A. Investigation of Some Antiviral N-Heterocycles as COVID 19 Drug: Molecular Docking and DFT Calculations. Int. J. Mol. Sci., 2020, 21(11), 3922.
[http://dx.doi.org/10.3390/ijms21113922] [PMID: 32486229]
(c) Ngo, S.T.; Quynh Anh Pham, N.; Thi Le, L.; Pham, D.H.; Vu, V.V. Computational determination of potential inhibitors of SARS-CoV-2 main protease. J. Chem. Inf. Model., 2020, 60(12), 5771-5780.
[http://dx.doi.org/10.1021/acs.jcim.0c00491] [PMID: 32530282]
(b) Hagar, M.; Ahmed, H.A.; Aljohani, G.; Alhaddad, O.A. Investigation of Some Antiviral N-Heterocycles as COVID 19 Drug: Molecular Docking and DFT Calculations. Int. J. Mol. Sci., 2020, 21(11), 3922.
[http://dx.doi.org/10.3390/ijms21113922] [PMID: 32486229]
(c) Ngo, S.T.; Quynh Anh Pham, N.; Thi Le, L.; Pham, D.H.; Vu, V.V. Computational determination of potential inhibitors of SARS-CoV-2 main protease. J. Chem. Inf. Model., 2020, 60(12), 5771-5780.
[http://dx.doi.org/10.1021/acs.jcim.0c00491] [PMID: 32530282]
[5]
Stebbing, J.; Phelan, A.; Griffin, I.; Tucker, C.; Oechsle, O.; Smith, D.; Richardson, P. COVID-19: combining antiviral and anti-inflammatory treatments. Lancet Infect. Dis., 2020, 20(4), 400-402.
[http://dx.doi.org/10.1016/S1473-3099(20)30132-8] [PMID: 32113509]
[http://dx.doi.org/10.1016/S1473-3099(20)30132-8] [PMID: 32113509]
[6]
(a) Siadati, S.A.; Rezvanfar, M.A.; Babanezhad, E.; Beheshti, A.; Payab, M. Harmony of operations of some vitamins in controlling the 2019-nCoV virus based on scientific reports. Chem. Rev. Lett., 2020, 3, 202-206.
(b) Grant, W.B.; Lahore, H.; McDonnell, S.L.; Baggerly, C.A.; French, C.B. J. L.; Bhattoa, H. P. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients, 2020, 12, 988.
[http://dx.doi.org/10.3390/nu12040988]
(b) Grant, W.B.; Lahore, H.; McDonnell, S.L.; Baggerly, C.A.; French, C.B. J. L.; Bhattoa, H. P. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients, 2020, 12, 988.
[http://dx.doi.org/10.3390/nu12040988]
[7]
(a) Siadati, S.A.; Afzali, M.; Sayyadi, M. Could silver nano-particles control the 2019-nCoV virus? An urgent glance to the past. Chem. Rev. Lett., 2020, 3, 9-11.
(b) Zachar, O. Formulations for COVID-19 Treatment via Silver Nanoparticles Inhalation Delivery., 2020.osf.io/adnyb
(c) Patel, M. Nanoparticle-based antimicrobial paper as spread-breaker for corona virus. Paper Tech. Int., 2020, 62, 20-25.
(b) Zachar, O. Formulations for COVID-19 Treatment via Silver Nanoparticles Inhalation Delivery., 2020.osf.io/adnyb
(c) Patel, M. Nanoparticle-based antimicrobial paper as spread-breaker for corona virus. Paper Tech. Int., 2020, 62, 20-25.
[8]
Elfiky, A.A.; Ribavirin, R.; Sofosbuvir, G. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci., 2020, 253, 117592.
[http://dx.doi.org/10.1016/j.lfs.2020.117592] [PMID: 32222463]
[http://dx.doi.org/10.1016/j.lfs.2020.117592] [PMID: 32222463]
[9]
Wang, M.; Cao, R.; Zhang, L.; Yang, X.; Liu, J.; Xu, M.; Shi, Z.; Hu, Z.; Zhong, W.; Xiao, G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res., 2020, 30(3), 269-271.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[10]
Eloy, P.; Solas, C.; Touret, F.; Mentré, F.; Malvy, D.; de Lamballerie, X.; Guedj, J. Dose rationale for favipiravir use in patients infected with SARS‐CoV‐2. Clin. Pharmacol. Ther., 2020, 108(2), 188-188.
[http://dx.doi.org/10.1002/cpt.1877] [PMID: 32350860]
[http://dx.doi.org/10.1002/cpt.1877] [PMID: 32350860]
[11]
(a) Li, G.; De Clercq, E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nat. Rev. Drug Discov., 2020, 19(3), 149-150.
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666]
(b) Zhu, Z.; Lu, Z.; Xu, T.; Chen, C.; Yang, G.; Zha, T.; Lu, J.; Xue, Y. Arbidol monotherapy is superior to lopinavir/ritonavir in treating COVID-19. J. Infect., 2020, 81(1), e21-e23.
[http://dx.doi.org/10.1016/j.jinf.2020.03.060] [PMID: 32283143]
(c) Chen, J.; Lin, S.; Niu, C.; Xiao, Q. Clinical evaluation of Shufeng Jiedu Capsules combined with umifenovir (Arbidol) in the treatment of common-type COVID-19: a retrospective study. Expet. Rev. Respir. Med., 2020, 1-9..
[http://dx.doi.org/10.1038/d41573-020-00016-0] [PMID: 32127666]
(b) Zhu, Z.; Lu, Z.; Xu, T.; Chen, C.; Yang, G.; Zha, T.; Lu, J.; Xue, Y. Arbidol monotherapy is superior to lopinavir/ritonavir in treating COVID-19. J. Infect., 2020, 81(1), e21-e23.
[http://dx.doi.org/10.1016/j.jinf.2020.03.060] [PMID: 32283143]
(c) Chen, J.; Lin, S.; Niu, C.; Xiao, Q. Clinical evaluation of Shufeng Jiedu Capsules combined with umifenovir (Arbidol) in the treatment of common-type COVID-19: a retrospective study. Expet. Rev. Respir. Med., 2020, 1-9..
[12]
Haviernik, J.; Štefánik, M.; Fojtíková, M.; Kali, S.; Tordo, N.; Rudolf, I.; Hubálek, Z.; Eyer, L.; Ruzek, D. Arbidol (Umifenovir): a broad-spectrum antiviral drug that inhibits medically important arthropod-borne flaviviruses. Viruses, 2018, 10(4), 184.
[http://dx.doi.org/10.3390/v10040184] [PMID: 29642580]
[http://dx.doi.org/10.3390/v10040184] [PMID: 29642580]
[13]
Annapurna, M. M. New stability indicating ultrafast liquid chromatographic method for the determination of umifenovir in tablets. Int. J Green Pharma. (IJGP), 2018, 12, 01..
[14]
Balakin, K.V.; Filosa, R.; Lavrenov, S.N.; Mkrtchyan, A.S.; Nawrozkij, M.B.; Novakov, I.A. Arbidol: a quarter-century after. Past, present and future of the original Russian antiviral. Russ. Chem. Rev., 2018, 87, 509.
[http://dx.doi.org/10.1070/RCR4791]
[http://dx.doi.org/10.1070/RCR4791]
[15]
Trofimov, F.A.; Tsyshkova, N.G.; Zotova, S.A.; Grinev, A.N. Synthesis of a new antiviral agent, arbidole. Pharm. Chem. J., 1993, 27, 75-76.
[http://dx.doi.org/10.1007/BF00772858]
[http://dx.doi.org/10.1007/BF00772858]
[16]
Granik, V.G.; Lyubchanskaya, V.M.; Mukhanova, T.I. The Nenitzescu reaction. Pharm. Chem. J., 1993, 27, 413-438.
[http://dx.doi.org/10.1007/BF00780660]
[http://dx.doi.org/10.1007/BF00780660]
[17]
Zhao, H.; Dietrich, J. Privileged scaffolds in lead generation. Expert Opin. Drug Discov., 2015, 10(7), 781-790.
[http://dx.doi.org/10.1517/17460441.2015.1041496] [PMID: 25959748]
[http://dx.doi.org/10.1517/17460441.2015.1041496] [PMID: 25959748]
[18]
Trofimov, F.A.; Tsyshkova, N.G.; Grinev, A.N. 2-Bromomethyl derivatives of benzofuran and indole and their reactions with some nucleophilic reagents. Chem. Heterocycl. Compd., 1973, 9, 282-285.
[http://dx.doi.org/10.1007/BF00944494]
[http://dx.doi.org/10.1007/BF00944494]
[19]
Chen, L.; Yu, X.; Li, M.; Li, Y.; Peng, C.; Li, X. Zhou. Z. Synthesis of antivirals mesylate arbidol, J Wuhan Inst. Tech, 2012, 34, 42-45.
[20]
Song, Y.; Zhao, Y. Gong. P. Synthesis of derivatives of N-alkyl-5-hydroxy-1H-indole-3-carboxylic ester hydrochloride. Zhongguo Xin Yao Zazhi, 2004, 13, 335-337.
[21]
Trofimov, F.A. Indole derivative having antiviral, interferon-inducing and immunomodulatory effects US Patent, 5198552A, 1993.
[22]
Grinev, A. N. Chlorohydrate of 1-methyl-2-phenylthiomethyl-3-carboethoxy-4 -dimethylaminomethyl-5-oxy-6-bromoindole having antivirus action and method for obtaining it, SU patent, 1685933, 1991.
[23]
Cao, Zhifei; Dong, Jun; Shi, Lin Process for preparation of arbidol hydrochloride from 3-iodo-4-nitrophenol Faming Zhuanli Shenqing, CN patent, 102351778A, 2012.
[24]
Monti, S.A. The Nentizescu Condensation of Ethyl 3-Aminocrotonate and 1,4-Benzoquinone. J. Org. Chem., 1996, 31, 2669-2672.
[http://dx.doi.org/10.1021/jo01346a503]
[http://dx.doi.org/10.1021/jo01346a503]
[25]
(a) Wright, Z.V.F.; Wu, N.C.; Kadam, R.U.; Wilson, I.A.; Wolan, D.W. Structure-based optimization and synthesis of antiviral drug Arbidol analogues with significantly improved affinity to influenza hemagglutinin. Bioorg. Med. Chem. Lett., 2017, 27(16), 3744-3748.
[http://dx.doi.org/10.1016/j.bmcl.2017.06.074] [PMID: 28689973]
(b) Li, X.; Wang, X.; Jiang, Q.; Chi, F.; Liu, Q.; Zhang, T. The delivery of arbidol by salt engineering: synthesis, physicochemical properties and pharmacokinetics. Drug Dev. Ind., 2017, 43, 151-159.
[http://dx.doi.org/10.1080/03639045.2016.1225755]
[http://dx.doi.org/10.1016/j.bmcl.2017.06.074] [PMID: 28689973]
(b) Li, X.; Wang, X.; Jiang, Q.; Chi, F.; Liu, Q.; Zhang, T. The delivery of arbidol by salt engineering: synthesis, physicochemical properties and pharmacokinetics. Drug Dev. Ind., 2017, 43, 151-159.
[http://dx.doi.org/10.1080/03639045.2016.1225755]
[26]
(a) Schols, D.; Ruchko, E.A.; Lavrenov, S.N.; Kachala, V.V.; Nawrozkij, M.B.; Babushkin, A.S. Structural analogs of umifenovir 2. The synthesis and antiHIV activity study of new regioisomeric (trans-2-phenylcyclopropyl)-1H-indole derivatives. Chem. Heterocycl. Compd., 2015, 51, 978-983.
[http://dx.doi.org/10.1007/s10593-016-1807-9]
(b) Balzarini, J.; Ruchko, E.A.; Zakharova, E.K.; Kameneva, I.Y.; Nawrozkij, M.B. Structural Analogs of Umifenovir. 1. Synthesis and Biological Activity of Ethyl 5-Hydroxy-1-Methyl-2-(Trans-2-Phenylcyclopropyl)-1H-Indole-3-Carboxylate. Chem Heterocycl Compd (N Y), 2014, 50(4), 489-495.
[http://dx.doi.org/10.1007/s10593-014-1499-y] [PMID: 32214417]
[http://dx.doi.org/10.1007/s10593-016-1807-9]
(b) Balzarini, J.; Ruchko, E.A.; Zakharova, E.K.; Kameneva, I.Y.; Nawrozkij, M.B. Structural Analogs of Umifenovir. 1. Synthesis and Biological Activity of Ethyl 5-Hydroxy-1-Methyl-2-(Trans-2-Phenylcyclopropyl)-1H-Indole-3-Carboxylate. Chem Heterocycl Compd (N Y), 2014, 50(4), 489-495.
[http://dx.doi.org/10.1007/s10593-014-1499-y] [PMID: 32214417]
[27]
(a) Brancato, V.; Peduto, A.; Wharton, S.; Martin, S.; More, V.; Di Mola, A.; Massa, A.; Perfetto, B.; Donnarumma, G.; Schiraldi, C.; Tufano, M.A.; de Rosa, M.; Filosa, R.; Hay, A. Design of inhibitors of influenza virus membrane fusion: synthesis, structure-activity relationship and in vitro antiviral activity of a novel indole series. Antiviral Res., 2013, 99(2), 125-135.
[http://dx.doi.org/10.1016/j.antiviral.2013.05.005] [PMID: 23707194]
(b) Rostami-Charati, F.; Hossaini, Z.; Sheikholeslami-Farahani, F.; Azizi, Z.; Siadati, S.A. Synthesis of 9H-furo [2,3-f]Chromene Derivatives by Promoting ZnO Nanoparticles. Comb. Chem. High Throughput Screen., 2015, 18(9), 872-880.
[http://dx.doi.org/10.2174/1386207318666150525094109] [PMID: 26004051]
(c) Hossaini, Z.; Rostami-Charati, F.; Ghambarian, M.; Siadati, S.A. Synthesis of a new class of phosphonate derivatives using a three component reaction of trialkylphosphites or triarylphosphites in water. PHOSPHORUS SULFUR, 2015, 190, 1177-1182.
[http://dx.doi.org/10.1080/10426507.2014.978329]
[http://dx.doi.org/10.1016/j.antiviral.2013.05.005] [PMID: 23707194]
(b) Rostami-Charati, F.; Hossaini, Z.; Sheikholeslami-Farahani, F.; Azizi, Z.; Siadati, S.A. Synthesis of 9H-furo [2,3-f]Chromene Derivatives by Promoting ZnO Nanoparticles. Comb. Chem. High Throughput Screen., 2015, 18(9), 872-880.
[http://dx.doi.org/10.2174/1386207318666150525094109] [PMID: 26004051]
(c) Hossaini, Z.; Rostami-Charati, F.; Ghambarian, M.; Siadati, S.A. Synthesis of a new class of phosphonate derivatives using a three component reaction of trialkylphosphites or triarylphosphites in water. PHOSPHORUS SULFUR, 2015, 190, 1177-1182.
[http://dx.doi.org/10.1080/10426507.2014.978329]
[28]
(a) Bakherad, M.; Keivanloo, A.; Omidian, M.; Samangooei, S. Synthesis of pyrrolo [2, 3-b] pyrazines through Sonogashira coupling reaction of 5, 6-dichloropyrazine-2, 3-dicarbonitrile with hydrazine, phenylacetylene and various aldehydes. J. Chem. Res., 2014, 38, 762-764.
[http://dx.doi.org/10.3184/174751914X14180425794376]
(b) Bakherad, M.; Keivanloo, A.; Samangooei, S.; Omidian, M. A phenyldithiocarbazate-functionalized polyvinyl chloride resin-supported Pd (II) complex as an effective catalyst for solvent-and copper-free Sonogashira reactions under aerobic conditions. J. Organomet. Chem., 2013, 740, 78-82.
[http://dx.doi.org/10.1016/j.jorganchem.2013.04.058]
(c) Bakherad, M.; Keivanloo, A.; Siavashi, M.; Omidian, M. Three-component synthesis of imidazo [1, 2-c] pyrimidines using silica sulfuric acid (SSA). Chin. Chem. Lett., 2014, 25, 149-151.
[http://dx.doi.org/10.1016/j.cclet.2013.10.013]
[http://dx.doi.org/10.3184/174751914X14180425794376]
(b) Bakherad, M.; Keivanloo, A.; Samangooei, S.; Omidian, M. A phenyldithiocarbazate-functionalized polyvinyl chloride resin-supported Pd (II) complex as an effective catalyst for solvent-and copper-free Sonogashira reactions under aerobic conditions. J. Organomet. Chem., 2013, 740, 78-82.
[http://dx.doi.org/10.1016/j.jorganchem.2013.04.058]
(c) Bakherad, M.; Keivanloo, A.; Siavashi, M.; Omidian, M. Three-component synthesis of imidazo [1, 2-c] pyrimidines using silica sulfuric acid (SSA). Chin. Chem. Lett., 2014, 25, 149-151.
[http://dx.doi.org/10.1016/j.cclet.2013.10.013]
[29]
(a) Siadati, S.A. A Theoretical Study on Stepwise- and Concertedness of the Mechanism of 1,3-Dipolar Cycloaddition Reaction Between Tetra Amino Ethylene and Trifluoro Methyl Azide. Comb. Chem. High Throughput Screen., 2016, 19(2), 170-175.
[http://dx.doi.org/10.2174/1386207319666151216145408] [PMID: 26673901]
(b) Siadati, S.A. An example of a stepwise mechanism for the catalyst-free 1, 3-dipolar cycloaddition between a nitrile oxide and an electron rich alkene. Tetrahedron Lett., 2015, 56, 4857-4863.
[http://dx.doi.org/10.1016/j.tetlet.2015.06.048]
(c) Siadati, S.A. The Effect of Position Replacement of Functional Groups on the Stepwise character of 1, 3-Dipolar Reaction of a Nitrile Oxide and an Alkene. Helv. Chim. Acta, 2016, 99, 273-280.
[http://dx.doi.org/10.1002/hlca.201500165]
(d)Zardoost, M.R.; Siadati, S.A. A theoretical study of substitution effect on an electrocyclization reaction. Comb. Chem. High Throughput Screen., 2013, 16(5), 408-412.
[http://dx.doi.org/10.2174/1386207311316050006] [PMID: 23330875]
[http://dx.doi.org/10.2174/1386207319666151216145408] [PMID: 26673901]
(b) Siadati, S.A. An example of a stepwise mechanism for the catalyst-free 1, 3-dipolar cycloaddition between a nitrile oxide and an electron rich alkene. Tetrahedron Lett., 2015, 56, 4857-4863.
[http://dx.doi.org/10.1016/j.tetlet.2015.06.048]
(c) Siadati, S.A. The Effect of Position Replacement of Functional Groups on the Stepwise character of 1, 3-Dipolar Reaction of a Nitrile Oxide and an Alkene. Helv. Chim. Acta, 2016, 99, 273-280.
[http://dx.doi.org/10.1002/hlca.201500165]
(d)Zardoost, M.R.; Siadati, S.A. A theoretical study of substitution effect on an electrocyclization reaction. Comb. Chem. High Throughput Screen., 2013, 16(5), 408-412.
[http://dx.doi.org/10.2174/1386207311316050006] [PMID: 23330875]
[30]
(a) Siadati, S.A. Beyond the alternatives that switch the mechanism of the 1, 3-dipolar cycloadditions from concerted to stepwise or vice versa: a literature review. Prog. React. Kinet. Mech., 2016, 41, 331-344.
[http://dx.doi.org/10.3184/146867816X14719552202168]
(b) Siadati, S.A.; Mahboobifar, A.; Nasiri, R. A theoretical study on the reaction pathways and the mechanism of 1,3- dipolar cycloaddition of vinyl acetylene and methyl azide. Comb. Chem. High Throughput Screen., 2014, 17(8), 703-708.
[http://dx.doi.org/10.2174/138620731708140922163855] [PMID: 24852164]
(c) Jasiński, R.; Dresler, E. On the Question of Zwitterionic Intermediates in the [3+ 2] Cycloaddition Reactions: A Critical Review. Organics, 2020, 1, 49-69.
[http://dx.doi.org/10.3390/org1010005]
[http://dx.doi.org/10.3184/146867816X14719552202168]
(b) Siadati, S.A.; Mahboobifar, A.; Nasiri, R. A theoretical study on the reaction pathways and the mechanism of 1,3- dipolar cycloaddition of vinyl acetylene and methyl azide. Comb. Chem. High Throughput Screen., 2014, 17(8), 703-708.
[http://dx.doi.org/10.2174/138620731708140922163855] [PMID: 24852164]
(c) Jasiński, R.; Dresler, E. On the Question of Zwitterionic Intermediates in the [3+ 2] Cycloaddition Reactions: A Critical Review. Organics, 2020, 1, 49-69.
[http://dx.doi.org/10.3390/org1010005]
[31]
Witschi, C.; Doelker, E. Residual solvents in pharmaceutical products: acceptable limits, influences on physicochemical properties, analytical methods and documented values. Eur. J. Pharm. Biopharm., 1997, 43, 215-242.
[http://dx.doi.org/10.1016/S0939-6411(96)00037-9]
[http://dx.doi.org/10.1016/S0939-6411(96)00037-9]
[32]
Daoudy, D. A. B.; Al-Khayat, M. A.; Karabet, F.; Al-Mardini, M. A. A robust static headspace GC-FID method to detect and quantify formaldehyde impurity in pharmaceutical excipients. J anal. Meth. chem., 2018.
[33]
Poceva Panovska, A.; Acevska, J.; Stefkov, G.; Brezovska, K.; Petkovska, R.; Dimitrovska, A. Optimization of HS-GC–FID–MS method for residual solvent profiling in active pharmaceutical ingredients using DoE. J. Chromatogr. Sci., 2016, 54(2), 103-111.
[PMID: 26290585]
[PMID: 26290585]
[34]
Fedorov, Y.V.; Fedorova, O.A.; Kalmykov, S.N.; Oshchepkov, M.S.; Nelubina, Y.V.; Arkhipov, D.E.; Zubenko, A.D. Potentiometric studies of complex formation of amidopyridine macrocycles bearing pendant arms with proton and heavy metal ions in aqueous solution. Polyhedron, 2017, 124, 229-236.
[http://dx.doi.org/10.1016/j.poly.2016.12.037]
[http://dx.doi.org/10.1016/j.poly.2016.12.037]
[35]
Liang, J.; Zhu, J.; Gong, L.; Liu, X.; Wang, B. Potentiometric titration for the high precision determination of active components in six types of chemical disinfectants. PLoS One, 2018, 13(9), e0203558.
[http://dx.doi.org/10.1371/journal.pone.0203558] [PMID: 30192844]
[http://dx.doi.org/10.1371/journal.pone.0203558] [PMID: 30192844]
[36]
(a) Siadati, S.A.; Payab, M.; Beheshti, A. Development of a reversed-phase HPLC method for determination of related impurities of Lenalidomide. Chem. Rev. Lett, 2020, 3, 61-64.
(b) Siadati, S. A.; Rezvanfar, M. A.; Payab, M.; Beheshti, A. Development and validation of a short runtime method for separation of trace amounts of 4-aminophenol, phenol, 3-nitrosalicylic acid and mesalamine by using HPLC system. Current. Chem. Lett., 2021, 9, 1-10.
[http://dx.doi.org/10.5267/j.ccl.2020.12.002]
(b) Siadati, S. A.; Rezvanfar, M. A.; Payab, M.; Beheshti, A. Development and validation of a short runtime method for separation of trace amounts of 4-aminophenol, phenol, 3-nitrosalicylic acid and mesalamine by using HPLC system. Current. Chem. Lett., 2021, 9, 1-10.
[http://dx.doi.org/10.5267/j.ccl.2020.12.002]
Related Journals
Current Computer-Aided Drug Design
Article Metrics
28
2