Synthesis of Tetrazole Tethered Tetrahydrobenzo [B] Thiophene-3-Carbonitrile by Isocyanide-Based Condensation
DOI:
https://doi.org/10.32628/IJSRST25122212Abstract
Tetrazole-tethered tetrahydrobenzo[b]thiophene-3-carbonitrile derivatives have gained significant attention due to their diverse biological and pharmaceutical applications. In this study, we present an efficient synthesis of tetrazoles using an isocyanide-based multicomponent condensation strategy. The reaction involves a nitrile as precursor, isocyanide, aldehyde, and a sulfur source under optimized catalytic conditions, leading to the formation of highly functionalized frameworks. Furthermore, the cyclization of the nitrile with sodium azide facilitates the introduction of the tetrazole moiety, enhancing the molecular complexity. The developed methodology provides a facile, high-yielding, and sustainable approach to constructing novel heterocyclic scaffolds with potential medicinal relevance.
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Akopyants, N. S.; Kimblin, N.; Secundino, N.; Patrick, R.; Peters, N.; Lawyer, P.; Dobson, D. E.; Beverley, S. M.; Sacks, D. L. Demonstration of Genetic Exchange during Cyclical Development of Leishmania in the Sand Fly Vector. Science. 2009, 324, 265-268.
WHO, Working to Overcome the Global Impact of Neglected Tropical Diseases, Stylys Pub Llc: Geneva, 2010. (b) Majumder, H. K. Drug Targets in Kinetoplastid Parasites; Springer Science+Business Media: New York, 2011.
Pimenta, P. F.; Turco, S. J.; McConville, M. J.; Lawyer, P. G.; Perkins, P. V.; Sacks, D. L. Stage-specific adhesion of Leishmania promastigotes to the sandfly midgut. Science 1992, 256, 1812-1815
(a) Chappuis, F.; Sundar, S.; Hailu, A.; Ghalib, H.; Alvar, J.; Boelaer, M. Visceral leishmaniasis: what are the needs for diagnosis, treatment and control? Nat. Rev. Microbiol. 2007, 5, 873–885. (b) Alvar, J.; Canavate, C.; Gutierrez- Solar, B.; Jimenez, M.; Lagnon, F.; Lopez-Velet, R.; Molina, R.; Moreno, J. Leishmania and human immunodeficiency virus coinfection: the first 10 years. Clin. Microbiol. Rev. 1997, 10, 298–319.
Bogdon C., Gessner, A., Solbach, W. and Rollinghoff, M. Invasion, control and persistence of Leishmania parasites Curr Opin Immunol. 1996. Vol. 8: 517-525.
(a) Sundar, S.; Rai, M. Advances in the treatment of leishmaniasis. Curr. Opin. Infect. Dis. 2002, 15, 593–598. (b) Pink, R.; Hudson, A.; Mouriès, M.-A.; Bendig, M. Opportunities and challenges in antiparasitic drug discovery. Nat. Rev. Drug Discov. 2005, 4, 727–740.
(a) Berman, J. ABLE: A New and Improved Amphotericin B for Visceral Leishmaniasis?. Am. J. Trop. Med. Hyg. 2009, 8,689–690. (b)Guerin, P. J.; Olliaro, P.; Sundar, S.; Boelaert, M.; Croft, S. L.; Desjeux, P.; Wasunna, K.; Bryceson, A.; D.; M. Visceral leishmaniasis: current status of control, diagnosis, and treatment, and a proposed research and development agenda. Lancet Infect. Dis. 2002, 2, 494–501.
Dorlo, T.; P.; C.; van Thiel, P.; A.; M.; Huitema, A.; D.; R.; Keizer, R.; J.; De Vries, H.; J.; C.; Beijnen, J.; H.; De Vries, P.; J. Pharmacokinetics of Miltefosine in Old World Cutaneous Leishmaniasis Patients. Antimicrob. Agents Chemother. 2008, 52, 2855–2860. (b) Sindermann, H.; Engel, J. Development of miltefosine as an oral treatment for leishmaniasis. Trans. R. Soc. Trop. Med. Hyg. 2006, 100(Suppl. 1):S17– S20.
Croft, S.; L.; Sundar, S.; Fairlam, A.; H. Drug Resistance in Leishmaniasis. Clin. Microbiol. Rev. 2006, 111–126. (b) Sundar, S. Drug resistance in Indian visceral leishmaniasis. Trop. Med. Int. Health 2001, 6, 849–854.
Cavalli, A.; Bolognesi, M. L. Neglected tropical diseases: multitarget-directed ligands in the search for novel lead candidates against Trypanosomia and Leishmania. J. Med. Chem. 2009, 52, 7339–7359.
Meunier, B. Hybrid molecules with a dual mode of action: dream or reality? Acc. Chem. Res. 2008, 41, 69–77.
Congreve, M.; Chessari, G.; Tisi, D.; Woodhead, A. J. Recent developments in fragment-based drug discovery. J. Med. Chem. 2008, 51, 3661–3680
Newman, D. J. Natural Products as Leads to Potential Drugs: An Old Process or the New Hope for Drug Discovery? J. Med. Chem. 2008, 51, 2589–2599
Rochaa, L. G.; Almeidab, J. R.; G. S.; Maceˆdob, R. O.; Barbosa-Filho J. M. A.review of natural products with antileishmanial activity. Phytomedicine 2005, 12, 514–535
Tietze, L.; F.; Bell, H.; P.; Chandrasekhar, S. Natural Product Hybrids as New Leads for Drug Discovery. Angew. Chem. Int. Ed. 2003, 42, 3996 – 4028.
Wilson, R. M.; Danishefsky, S. J. Small molecule natural products in the discovery of therapeutic agents: the synthesis connection. J. Org. Chem. 2006, 71, 8329–8351.
Rao K V; Kasanah N; Wahyuono S; Tekwani B L; Schinazi R F; Hamann M T; J. Nat. Prod. 2004, 67, 1314.
W H Jiao, H Gao , C Y Li, F Zhao, R W Jiang, Y Wang, G X Zhou, X S Yao, J. Nat. Prod. 2010, 73, 167.
R A Davis, A R Carroll, R J Quinn J. Nat. Prod. 1998, 61, 61.
Y Inuma, S Kozawa, H Ishiyama, M Tsuda, E Fukushi, J Kawabata, J Fromont, J Kobayashi, J. Nat. Prod. 2005, 68, 1109.
E V Costa, M L B Pinheiro, C M Xavier, J R A Silva, A C F Amaral, A D L Souza, A Barison,F R Campos,A G Ferreira, G M C Machado, L L P Leon, J. Nat. Prod. 2006, 69, 292.
Herr, R. J. Bioorg. Med. Chem. 2002, 10, 3379.
G. D. Smith, J. Zabrocki, T.A. Flak, G.R. Marshal, Int. J. Peptide Protein Res., 1991, 37, 191-197.
K-L. Yu, R.L.Johnson , J. Org. Che., 1987, 52, 2051-2059.
J.V. Duncia , A.T. Chiu, D.J. Carini, G.B. Gregory, J.Med. Chem., 1990, 33, 1312-29.
Dahlof B, Deveruex RB, Kjeldsen SE, Lancet 2002, 359, 995-1003.
Mosmann T, J.Immunol.Meth; 1983, 65, 55-63.
L. V. Myznikov, A. Hrabalek, G. I. Koldobskii, Chem. Het.Compounds, 2007, 43, 1-9.
M. J. Schocken, R. W. Creekmore, G.Theodoridis, G. J. Nystrom, R. A. Robinson, Appl.Environ. Microbiol., 1989, 55(5), 1220-1222.
R. N. Butter , A. R Katritzky, C. W. Rees, Comprehensive heterocyclic chemistry, Vol.5: Part 4A, Pergamon Press, New York, 1984, 001-791.
T. Mavromoustakos , A. Kolocouris, M. Zervou , P. Roumelioti , J. Matsoukas, R.Weisemann, J. Med. Chem., 1999, 42, 1714-1722.
N. Mekni, A. Bakloiti, J. Fluorine Chem., 2008, 129, 1073-1075
J.H. Toney , P.M.D. Fitzgerald, N. Grover-Sharma, S.H.Olson, W.J. May, J.G. Sundelof, D. E. Venderwall, K.A. Cleary, S. K. Grant, J.K. Wu, J.W. Kozarich, D. L. Pompliano , G.G. Hammond , Chem. Biol., 1998, 5, 185-196.
Y. Tamura, F. Watanabe, T. Nakatani, K. Yasui, M. Fuji, T. Komurasaki, H. Tsuzuki, R. Maekawa, T. Yoshioka, K. Kawada, K. Sugita, M. Ohtani, J. Med. Chem., 1998, 41, 640-649.
S. J. Lim , Y. Sunohara, H. Matsumoto, J. Pestic. Sci., 2007, 32, 249-254.
(a) A Domling, I Ugi, Angew. Chem., Int. Ed. 39, 2000, 3168. (b) J D Sunderhaus, S F Martin, Chem.Eur. J. 2009, 15, 1300. (c) A Domling, Chem. Rev. 2006,106, 17.
Huber, W.; Koella, J. C. A comparison of three methods of estimating EC50 in studies of drug resistance of malaria parasites Acta Trop., 1993, 55, 257-261
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