A facile atom – economical synthesis of highly substituted pyrazolo-N-methyl-piperidine grafted spiro-indenoquinoxaline pyrrolidine heterocycles via a sequential multicomponent reaction

References

• (a) Trost, B. M. The Atom Economy – A Search for Synthetic Efficiency. Science 1991, 254, 1471–1477. DOI: 10.1126/science.1962206.
   PubMed Web of Science ®Google Scholar
  (b) Schreiber, S. L. Target-Oriented and Diversity-Oriented Organic Synthesis in Drug Discovery. Science 2000, 287, 1964–1969. DOI: 10.1126/science.287.5460.1964.
   PubMed Web of Science ®Google Scholar
• (a) Ibarra, I. A.; Islas-Jacome, A.; Gonzalez-Zamora, E. Synthesis of Polyheterocycles via Multicomponent Reactions. Org. Biomol. Chem. 2018, 16, 1402–1418. DOI: 10.1039/c7ob02305g.
   PubMed Web of Science ®Google Scholar
  (b) Biggs-Houck, J. E.; Younai, A.; Shaw, J. T. Recent Advances in Multicomponent Reactions for Diversity-Oriented Synthesis. Curr. Opin. Chem. Biol. 2010, 14, 371–382. DOI: 10.1016/j.cbpa.2010.03.003.
   PubMed Web of Science ®Google Scholar
  (c) Rotstein, B. H.; Zaretsky, S.; Rai, V.; Yudin, A. K. Small Heterocycles in Multicomponent Reactions. Chem. Rev. 2014, 114, 8323–8359. DOI: 10.1021/cr400615v.
   PubMed Web of Science ®Google Scholar
• Grigg, R.; Sridharan, V. In Advances in Cycloaddition; Curran, D. P., Ed.; Jai: London, 1993;Vol. 3, p 161.
   Google Scholar
• (a) Gothelf, K. V.; Jorgensen, K. A. Asymmetric 1,3-Dipolar Cycloaddition Reactions. Chem. Rev. 1998, 98, 863–910. DOI: 10.1021/cr970324e.
   PubMed Web of Science ®Google Scholar
  (b) Coldham, I.; Hufton, R. Intramolecular Dipolar Cycloaddition Reactions of Azomethine Ylides. Chem. Rev. 2005, 105, 2765–2810. DOI: 10.1021/cr040004c.
   PubMed Web of Science ®Google Scholar
  (c) Ryan, J. H. 1,3 Dipolar Cycloaddition Reactions of Azomethineylides. Arkivoc. 1 2015, 160–183. DOI: 10.3998/ark.5550190.p008.928
   Google Scholar
• O’Hagan, D. Pyrrole, Pyrrolidine, Pyridine, Piperidine, Andtropane Alkaloids. Nat. Prod. Rep. 2000, 17, 435–446. DOI: 10.1039/a707613d.
   PubMed Web of Science ®Google Scholar
• (a) Zhang, H.; Wu, J. S.; Peng, F. The Use of Spirocyclic Scaffolds in Drug Discovery. Anticancer Drugs 2008, 19, 125–132. DOI: 10.1016/j.bmcl.2014.06.081.
   PubMed Web of Science ®Google Scholar
  (b) Young, J. R.; Eid, R.; Turner, C.; Devita, R. J.; Kurtz, M. M.; Tsao, K. L.; Chicchi, G. G.; Wheeldon, A.; Carlson, E.; Mills, S. G. Pyrrolidine-carboxamides and Oxadiazoles as Potent hNK1 Antagonists. Bioorg. Med. Chem. Lett. 2007, 17, 5310–5315. DOI: 10.1016/j.bmcl.2007.08.028.
   PubMed Web of Science ®Google Scholar
• Abou-Gharbia, M. A.; Doukas, P. H. Synthesis of Tricyclic Aryl Spiro Compounds as Potential Antileukemic and Anticonvulsant Agents. Heterocycles 1979, 12, 637–640. DOI: 10.3987/R-1979-05-0637.
   Web of Science ®Google Scholar
• Pandey, S. H.; Shukla, S. H.; Pandey, D.; Srivastava, R. S. Studies on Anticonvulsant Agents Achievements and Prospects. Russ. Chem. Rev. 2011, 80, 187–208. DOI: 10.1070/RC2011v080n02ABEH004185.
   Web of Science ®Google Scholar
• Lundahl, K.; Schut, J.; Schlatmann, J. L. M. A.; Paerels, G. B.; Peters, A. Synthesis and Antiviral Activities of Adamantane Spiro Compounds. 1. Adamantane and Analogous Spiro-3′-pyrrolidines. J. Med. Chem. 1972, 15, 129–132. DOI: 10.1021/jm00272a003.
   PubMed Web of Science ®Google Scholar
• Tenthorey, P. A.; Ronfeld, R. A.; Feldman, H. S.; Sandberg, R. V.; Mcmaster, P. D.; Smith, E. R. New Antiarrhythmic agents. 4. 1′-(Aminoalkyl)-1,2,3,4-tetrahydronaphthalene-1-spiro-3′-pyrrolidine-2′,5′-dione derivatives. J. Med. Chem. 1981, 24, 47–53. DOI: 10.1021/jm00133a011.
   PubMed Web of Science ®Google Scholar
• Obniska, J.; Zagorska, A. Synthesis and Anticonvulsant Properties of New N-(4-Arylpiperazin-1-yl)-Methyl Derivatives 3-Aryl Pyrrolidine-2,5-Dione and 2-Aza-Spiro[4.4]Nonane-1,3-Dione. Farmacocta. 2003, 58, 1227–1234. DOI: 10.1016/S0014-827X(03)00187-3.
   PubMedGoogle Scholar
• Kornet, M. J.; Thio, A. P. Oxindole-3-Spiropyrrolidines and -Piperidines. Synthesis and Local Anesthetic Activity. J. Med. Chem. 1976, 19, 892–898. DOI: 10.1021/jm00229a007.
   PubMed Web of Science ®Google Scholar
• Hussein, E. M.; Abdel-Monem, M. I. Regioselective Synthesis and Anti-inflammatory Activity of Novel dispiro[pyrazolidine-4,3′-pyrrolidine-2′,3″-indoline]-2″,3,5-triones. Arkivoc. 2011, 10, 85–98. DOI: 10.3998/ark.5550190.0012.a07.
   Google Scholar
• Pearson, W. H.; In Studies in Natural Product Chemistry; Rahman, A. U. Ed.; Elsevier: Amsterdam, 1998; Vol. 1, pp 323–358
   Google Scholar
• Pharmaceutical Sales 2009. Drug information online, Drugs.com. April 5, 2011. http://www.drugs.com/top200_units.html.
   Google Scholar
• Singh, A. K.; Chawla, R.; Rai, A.; Yadav, L. D. S. NHC-catalysed Diastereoselective Synthesis of Multifunctionalised Piperidines via Cascade Reaction of Enals with Azalactones. Chem. Commun. 2012, 48, 3766–3768. DOI: 10.1039/C2CC00069E..
   PubMed Web of Science ®Google Scholar
• (a) Pereira, J. A.; Pessoa, A. M.; Natalia, M.; Cordeiro, D. S.; Fernandes, R.; Prudenicio, C.; Noronha, J. P.; Vieira, M. Quinoxaline, Its Derivatives and Applications: A State of the Art Review. Eur. J. Med. Chem. 2015, 97, 664–672. DOI: 10.1016/j.ejmech.2014.06.058.
   PubMed Web of Science ®Google Scholar
  (b) Naim, M. J.; Alam, O.; Nawaz, F.; Alam, M.; Alam, P. Current Status of Pyrazole and Its Biological Activities. J Pharm. Bioallied Sci. 2016, 8, 2–17. DOI: 10.4103/0975-7406.171694.
   PubMed Web of Science ®Google Scholar
• Saloni, P.; Bhumika, P.; Christophe, P.; Hardik, B. Design,Synthesis and Anti-HIV Activity of Novel Quinoxaline Derivatives. Eur. J. Med. Chem. 2016, 117, 230–240. DOI: 10.1016/j.ejmech.2016.04.019
   PubMed Web of Science ®Google Scholar
• (a) Guillon, J.; Forfar, I.; Mamani-Matsuda, M.; Desplat, V.; Saliège, M.; Thiolat, D.; Massip, S.; Tabourier, A.; Léger, J.-M.; Dufaure, B.; et al. Synthesis, Analytical Behaviour and Biological Evaluation of New 4-Substituted Pyrrolo[1,2-a]quinoxalines as Antileishmanial Agents. Bioorg. Med. Chem. 2007, 15, 194–210. DOI: 10.1016/j.bmc.2006.09.068.
   PubMed Web of Science ®Google Scholar
  (b) Cogo, J.; Kaplum, V.; Sangi, D. P.; Ueda-Nakamura, T.; Corrêa, A. G.; Nakamura, C. VSynthesis and Biological Evaluation of Novel 2,3-Disubstituted Quinoxaline Derivatives as Antileishmanial and Antitrypanosomal Agent. Eur. J. Med. Chem. 2015, 90, 107–123. DOI: 10.1016/j.ejmech.2014.11.018.
   PubMed Web of Science ®Google Scholar
  (c) Barea, C.; Pabón, A.; Pérez-Silanes, S.; Galiano, S.; Gonzalez, G.; Monge, A.; Deharo, E.; Aldana, I. New Amide Derivatives of Quinoxaline 1,4-Di-N-oxide with Leishmanicidal and Antiplasmodial Activities. Molecules 2013, 18, 4718–4727. DOI: 10.3390/molecules18044718
   PubMed Web of Science ®Google Scholar
• (a) Rangisetty, J. B.; Gupta, C. N. V. H. B.; Prasad, A. L.; Srinivas, P.; Sridhar, N.; Parimoo, P.; Veeranjaneyulu, A. Synthesis of New Arylaminoquinoxalines and Their Antimalarial Activity in miceJ. J. Pharm. Pharmacol. 2001, 53, 1409–1413. DOI: 10.1211/0022357011777765.
   PubMed Web of Science ®Google Scholar
  (b) Quiliano, M.; Aldana, I. Quinoxaline and Aryl Aminoalcohol Derivatives as Antiplasmodial and Leishmanicidal Agents: A Review of Our First Ten Years in the Field. Rev. Virtual Quim. 2013, 5, 1120–1133. DOI: 10.5935/1984-6835.20130081.
   Google Scholar
   (c) Vaidya, A. B.; Morrisey, M.; Zhang, Z.; Das, S.; Daly, T. M.; Otto, T. D.; Spillman, N. J.; Wyvratt, M.; Siegl, P.; Marfurt, J.; Wirianata; et al. Pyrazole Amide Compounds Are Potent Antimalarials That Target Na Homeostasis in Intraerythrocytic Plasmodium Falciparam. Nat.Comm. 2014, 5, 1–10. DOI: 10.1038/ncomms6521.
   Web of Science ®Google Scholar
• (a) Hassan, S. Y.; Khattab, S. N.; Bekhit, A. A.; Amer, A. Synthesis of 3-Benzyl-2-substituted Quinoxalines as Novel Monoamine Oxidase A Inhibitors. Bioorg. Med. Chem. Lett. 2006, 16, 1753–1756. DOI: 10.1016/j.bmcl.2005.11.088.
   PubMed Web of Science ®Google Scholar
  (b) Abdel-Aziz, M.; Abuo-Rahma, G. D.; Hassan, A. A. Synthesis of Novel Pyrazole Derivatives and Evaluation of Their Antidepressant and Anticonvulsant Activities. Eur. J. Med. Chem. 2009, 44, 3480–3487. DOI: 10.1016/j.ejmech.2009.01.032.
   PubMed Web of Science ®Google Scholar
• Danylkova, N. O.; Alcala, S. R.; Pomeranz, H. D.; McLoon, L. K. Neuroprotective Effects of Brimonidine Treatment in a Rodent Model of Ischemic Optic Neuropathy. Exp. Eye Res. 2007, 84, 293–301. DOI: 10.1016/j.exer.2006.10.002.
   PubMed Web of Science ®Google Scholar
• Mohanasundaram, U. M.; Chitkara, R.; Krishna, G. Smoking Cessation Therapy with Varenicline. Int. J. Chron. Obstruct. Pulmon. Dis. 2008, 3, 239–251. DOI: 10.2147/copd.s1848.
   PubMedGoogle Scholar
• Suresh Babu, A. R.; Raghunathan, R.; Gayatri, G.; Narahari Sastry, G. A. Highly Regioselective Synthesis of 1-N-Methyl-Spiro-[2.3′]-Oxindole-Spiro-[3.2″]-Indane-1″,3″-Dione-4-Aryl-Pyrrolidines through 1,3-Dipolar Cycloaddition Protocol. J. Heterocycl. Chem. 2006, 43, 1467–1472. DOI: 10.1002/jhet.5570430609.
   Web of Science ®Google Scholar
• Suresh Babu, A. R.; Raghunathan, R. A. Facile One-Pot Synthesis of Ferrocene Based Spiro-Pyrrolidines/Pyrrolizidines through 1,3-Dipolar Cycloaddition Reaction. Synth. Commun. 2010, 40, 2311–2319. DOI: 10.1080/00397910903243765.
   Google Scholar
• Suresh Babu, A. R.; Gavaskar, D.; Raghunathan, R. A Facile Synthesis of Novel Ferrocenegrafted Spiro-Indenoquinoxalinepyrrolizidines via One-Pot Multicomponent-[3 + 2]-Cycloadditionof Azomethine Ylides. Tetrahedron Lett. 2012, 53, 6676–6681. DOI: 10.1016/j.tetlet.2012.09.104.
   Web of Science ®Google Scholar
• Suresh Babu, A. R.; Gavaskar, D.; Raghunathan, R. An Expedient Ultrasonic-Assisted One- Pot Four Component Synthesis of Novel Ferrocene Grafted Pyrrolidine Heterocycles Via [3 + 2]-cycloaddition of Azomethine Ylides. J. Organometallic Chem. 2013, 745, 409–416. DOI: 10.1016/j.tetlet.2012.09.104.
   Web of Science ®Google Scholar
• Gavaskar, D.; Suresh Babu, A. R.; Raghunathan, R.; Dharani, M.; Balasubramanian, S. Balasubramanian SIonic Liquid Accelerated Multicomponent Sequential Assembly of Ferrocene Grafted Spiro-Heterocyles. J. Organomet. Chem 2014, 768, 128–135. DOI: 10.1016/j.jorganchem.2014.06.015.
   Web of Science ®Google Scholar
• Babu, A. R. S.; Raghunathan, R.; Mathivanan, N.; Omprabhac, G.; Velmurugan, D.; Raghu, R. Synthesis, Characterization, Anti-Microbial Activity and Docking Studies of Novel Dispirooxindolopyrrolidines. Curr. Chem. Biol. 2008, 2, 312–320. DOI: 10.2174/187231308785739729.
   Google Scholar
• Babu, A. R. S.; Raghunathan, R.; Kumaresan, K.; Raaman, N. Synthesis, Characterization and Anti-Microbial Activity of Novel Dispirooxindolopyrrolizidines. Curr. Chem. Biol. 2009, 3, 112–123. DOI: 10.2174/2212796810903010112.
   Google Scholar
• Ghalib, R. M.; Hashim, R.; Sulaiman, O.; Hemamalini, M.; Fun, H. K. 11H-Indeno-[1,2-b]quinoxalin-11-one. Acta. Crystallogr. Sect. E. Struct. Rep. Online. 2010, E66, o1494. DOI: 10.1107/S1600536810019252.
   Google Scholar
• Gavaskar, D.; Babu, A. R. S.; Raghunathan, R.; Dharani, M.; Balasubramanian, S. An Expedient Sequential One-pot Four Component Synthesis of Novel Steroidal Spiro-pyrrolidine Heterocycles in Ionic Liquid. Steroids 2016, 109, 1–6. DOI: 10.1016/j.steroids.2016.02.010.
   PubMed Web of Science ®Google Scholar
• Vishnu Priya, R.; Suresh, J.; Sivakumar, S.; Ranjith Kumar, R.; Sankaranarayanan, R. Synthesis, Spectroscopic and Docking Studies of Napthyl Substituted Di-Spiro Octahydroindolizine. Phys. Rev. Res. Int. 2013, 3, 479–489. https://journalpsij.com/index.php/PSIJ/article/view/23101.
   Google Scholar
• Wojcicka, A.; Becan, L. Synthesis and Biological Activity of Pyrazolo[4,3-c] Heterocyclic Derivatives: A Mini Review. MROC. 2015, 12, 298–309. DOI: 10.2174/1570193X12666150930224649.
   Google Scholar
• McElvain, S. M.; Rorig, K. Piperidine Derivatives; the Condensation of Aromatic Aldehydes with l-Methyl-4-piperidone. J. Am. Chem. Soc. 1948, 70, 1820–1825. DOI: 10.1021/ja01185a051.
   PubMed Web of Science ®Google Scholar