Main Article Content
Abstract
A series of imidazo[1,2-a]pyridines were synthesized by the reaction of α-chloroacetophenone and 2-aminopyridine under catalyst and solvent free condition. The synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral data. These imidazo[1,2-a]pyridines were screened for anti-inflammatory activity by carrageenan induced rat hind paw edema model. Good anti-inflammatory activity was shown by few compounds. The antibacterial activity was studied against two Gram-positive bacteria S. aureus and B. subtilis, two Gram-negative bacteria E. coli and S. typhi and antifungal activity against P. chrysogenum, F. moneliforme, A. flavus and A. niger. All the synthesized compounds were desplayed good antimicrobial and antifungal activities. Some of the compounds were shown higher antibacterial activity than reference drug penicillin.
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References
- C. Enguehard-Gueiffier and A. Gueiffier, Recent Progress in the Pharm-acology of Imidazo[1,2-a]pyridines, Mini Rev. Med. Chem., 7, 888 (2007); https://doi.org/10.2174/138955707781662645
- G. Song, Y. Zhang and X. Li, Rhodium and Iridium Complexes of Abnormal N-Heterocyclic Carbenes Derived from Imidazo[1,2-a]-pyridine, Organometallics, 27, 1936 (2008); https://doi.org/10.1021/om800109a
- Z. Tashrifi, M. Mohammadi-Khanaposhtani, B. Larijani and M. Mahdavi, C3-Functionalization of Imidazo[1,2-a]pyridines, Eur. J. Org. Chem., 2020, 269 (2020); https://doi.org/10.1002/ejoc.201901491
- C. Enguehard, J.L. Renou, H. Allouchi, J.M. Leger and A. Gueiffier, Synthesis of Diaryl-Substituted Imidazo[1, 2-a]pyridines Designed as Potential Aromatase Inhibitors, Chem. Pharm. Bull. (Tokyo), 48, 935 (2000); https://doi.org/10.1248/cpb.48.935
- M. Marcinkowska, M. Kolaczkowski, K. Kamilski, A. Bucki, M. Pawlowski, A. Siwek, T. Karcz, B. Mordyl, G. Starowicz, P. Kubowicz, E. Pekala, A. Wesolowska, J. Samochowiec, P. Mierzejewski and P. Bienkowski, Design, Synthesis and Biological Evaluation of Fluorinated Imidazo[1,2-a]pyridine Derivatives with Potential Anti-psychotic Activity, Eur. J. Med. Chem., 124, 456 (2016); https://doi.org/10.1016/j.ejmech.2016.08.059
- W. An, W. Wang, T. Yu, Y. Zhang, Z. Miao, T. Meng and J. Shen, Discovery of Novel 2-Phenyl-imidazo[1,2-a]pyridine Analogues Targeting Tubulin Polymerization as Antiproliferative Agents, Eur. J. Med. Chem., 112, 367 (2016); https://doi.org/10.1016/j.ejmech.2016.02.004
- B. Jadhav, R. Kenny, Y. Nivid, M. Mandewale and R. Yamgar, Synthesis and Evaluation of Antituberculosis Activity of Substituted 2,7-Dimethylimidazo[1,2-a]pyridine-3-Carboxamide Derivatives, Open J. Med. Chem., 6, 59 (2016); https://doi.org/10.4236/ojmc.2016.64006
- S. Hemasrilatha, K. Sruthi, A. Manjula and V.H. Babu, Synthesis and Anti-Inflammatory Activity of Imidazo[1,2-a]pyridinyl/Pyrazinyl Benzamides and Acetamides, Indian J. Chem., 51B, 981 (2012).
- W. Xhiqing, P. Yinyin and Z. Xiangge, Synthesis of 3-Arylimidazo[1,2-a]pyridines by a Catalyst-Free Cascade Process, Synthesis, 2011, 2255 (2011); https://doi.org/10.1055/s-0030-1260669
- F. Goktas, N. Cesur, D. Satana and M. Uzun, Synthesis of Novel Imidazo[1,2-a]pyridines and Evaluation of their Antifungal Activities, Turk. J. Chem., 38, 581 (2014); https://doi.org/10.3906/kim-1307-14
- T.H. Al-Tel, R.A. Al-Qawasmeh and R. Zaarour, Design, Synthesis and in vitro Antimicrobial Evaluation of Novel Imidazo[1,2 a]pyridine and Imidazo[2,1-b][1,3]benzothiazole Motifs, Eur. J. Med. Chem., 46, 1874 (2011); https://doi.org/10.1016/j.ejmech.2011.02.051
- S. Marhadour, P. Marchand, F. Pagniez, M.-A. Bazin, C. Picot, O. Lozach, S. Ruchaud, M. Antoine, L. Meijer, N. Rachidi and P. Le Pape, Synthesis and Biological Evaluation of 2,3-diarylimidazo[1,2-a]-pyridines as Antileishmanial Agents, Eur. J. Med. Chem., 58, 543 (2012); https://doi.org/10.1016/j.ejmech.2012.10.048
- A.J. Stasyuk, M. Banasiewicz, M.K. Cyranski and D.T. Gryko, Imidazo[1,2-a]pyridines Susceptible to Excited State Intramolecular Proton Transfer: One-Pot Synthesis via an Ortoleva-King Reaction, J. Org. Chem., 77, 5552 (2012); https://doi.org/10.1021/jo300643w
- L. Cai, F.T. Chin, V.W. Pike, H. Toyama, J.S. Liow, S.S. Zoghbi, K. Modell, E. Briard, H.U. Shetty, K. Sinclair, S. Donohue, D. Tipre, M.P. Kung, C. Dagostin, D.A. Widdowson, M. Green, W. Gao, M.M. Herman, M. Ichise and R.B. Innis, Synthesis and Evaluation of Two 18F-Labeled 6-Iodo-2-(4¢-N,N-dimethylamino)phenylimidazo[1,2-a]-pyridine Derivatives as Prospective Radioligands for b-Amyloid in Alzheimer's Disease, J. Med. Chem., 47, 2208 (2004); https://doi.org/10.1021/jm030477w
- Y. Zhang, Z. Chen, W. Wu, Y. Zhang and W. Su, CuI-Catalyzed Aerobic Oxidative a-Aminaton Cyclization of Ketones to Access Aryl or Alkenyl-Substituted Imidazoheterocycles, J. Org. Chem., 78, 12494 (2013); https://doi.org/10.1021/jo402134x
- I.I. Roslan, K.-H. Ng, J.-E. Wu, G.-K. Chuah and S. Jaenicke, Synthesis of Disubstituted 3-Phenylimidazo[1,2-a]pyridines via 2-Aminopyridine/CBrCl3 a-Bromination Shuttle, J. Org. Chem., 81, 9167 (2016); https://doi.org/10.1021/acs.joc.6b01714
- X. Han, C. Ma, Z. Wu and G. Huang, Zinc Iodide Catalyzed Synthesis of 3-Aminoimidazo[1,2-a]pyridines from 2-Aminopyridines and a-Amino Carbonyl Compounds, Synthesis, 48, 351 (2016); https://doi.org/10.1055/s-0035-1560375
- A.L. Rousseau, P. Matlaba and C.J. Parkinson, Multicomponent Synthesis of Imidazo[1,2-a]pyridines using Catalytic Zinc Chloride, Tetrahedron Lett., 48, 4079 (2007); https://doi.org/10.1016/j.tetlet.2007.04.008
- A.L. Krasovsky, V.G. Nenajdenko and E.S. Balenkova, A Facile Access to 2-CF3-Imidazo[1,2-a]pyridines, Synthesis, 1379 (2002); https://doi.org/10.1055/s-2002-33106
- Z.-H. Ren, Z.-H. Guan, M.-N. Zhao, Y. Yi and Y.-Y. Wang, Copper-Catalyzed Aerobic Oxidative Cyclization of Ketoxime Acetates with Pyridines for the Synthesis of Imidazo[1,2-a]pyridines, Synthesis, 48, 1920 (2016); https://doi.org/10.1055/s-0035-1561950
- R. Yan, G. Huang, H. Yan, S. Yang, X. Gao, K. Zhou and C. Ma, Iron(II)-Catalyzed Denitration Reaction: Synthesis of 3-Methyl-2-arylimidazo-[1,2-a]pyridine Derivatives from Aminopyridines and 2-Methylnitro-olefins, Synlett, 23, 2961 (2012); https://doi.org/10.1055/s-0032-1317685
- S.K. Guchhait, A.L. Chandgude and G. Priyadarshani, CuSO4-Glucose for in situ Generation of Controlled Cu(I)-Cu(II) Bicatalysts: Multi-component Reaction of Heterocyclic Azine and Aldehyde with Alkyne and Cycloisomerization toward Synthesis of N-Fused Imidazoles, J. Org. Chem., 77, 4438 (2012); https://doi.org/10.1021/jo3003024
- Y. Wang, B. Frett and H.-Y. Li, Efficient Access to 2,3-Diarylimidazo-[1,2-a]pyridines via a One-Pot, Ligand-Free, Palladium-Catalyzed Three-Component Reaction under Microwave Irradiation, Org. Lett., 16, 3016 (2014); https://doi.org/10.1021/ol501136e
- M. Adib, H. Bijanzadeh, A. Mohamadi, E. Sheikhi and S. Ansari, Microwave-Assisted, One-Pot Reaction of Pyridines, a-Bromoketones and Ammonium Acetate: An Efficient and Simple Synthesis of Imidazo[1,2-a]pyridines, Synlett, 1606 (2010); https://doi.org/10.1055/s-0029-1219962
- K.C. Chunawala, G. Joshi, E. Suresh and S. Adimurthy, Thermal and Microwave-Assisted Rapid Syntheses of Substituted Imidazo[1,2-a]-pyridines Under Solvent- and Catalyst-Free Conditions, Synthesis, 635 (2011); https://doi.org/10.1055/s-0030-1258405
- B.S. Santaniello, M.J. Price and J.K. Murray Jr., Synthesis and Characterization of 2-Phenylimidazo[1,2-a]pyridine: A Privileged Structure for Medicinal Chemistry, J. Chem. Educ., 94, 388 (2017); https://doi.org/10.1021/acs.jchemed.6b00286
- C.A. Winter, E.A. Risley and W.G. Nuss, Carrageenin-Induced Edema in Hind Paw of the Rat as an Assay for Antiinflammatory Drugs, Proc. Soc. Exp. Biol. Med., 111, 544 (1962); https://doi.org/10.3181/00379727-111-27849
- C.H. Collins, Microbiological Mthods, Butterworth: London, p. 364 (1967).
- R.J. Cruikshank, P. Durgid and R.R. Swain, Medical Microbiology, Churchill: Livingstone, vol. 1 (1998).
References
C. Enguehard-Gueiffier and A. Gueiffier, Recent Progress in the Pharm-acology of Imidazo[1,2-a]pyridines, Mini Rev. Med. Chem., 7, 888 (2007); https://doi.org/10.2174/138955707781662645
G. Song, Y. Zhang and X. Li, Rhodium and Iridium Complexes of Abnormal N-Heterocyclic Carbenes Derived from Imidazo[1,2-a]-pyridine, Organometallics, 27, 1936 (2008); https://doi.org/10.1021/om800109a
Z. Tashrifi, M. Mohammadi-Khanaposhtani, B. Larijani and M. Mahdavi, C3-Functionalization of Imidazo[1,2-a]pyridines, Eur. J. Org. Chem., 2020, 269 (2020); https://doi.org/10.1002/ejoc.201901491
C. Enguehard, J.L. Renou, H. Allouchi, J.M. Leger and A. Gueiffier, Synthesis of Diaryl-Substituted Imidazo[1, 2-a]pyridines Designed as Potential Aromatase Inhibitors, Chem. Pharm. Bull. (Tokyo), 48, 935 (2000); https://doi.org/10.1248/cpb.48.935
M. Marcinkowska, M. Kolaczkowski, K. Kamilski, A. Bucki, M. Pawlowski, A. Siwek, T. Karcz, B. Mordyl, G. Starowicz, P. Kubowicz, E. Pekala, A. Wesolowska, J. Samochowiec, P. Mierzejewski and P. Bienkowski, Design, Synthesis and Biological Evaluation of Fluorinated Imidazo[1,2-a]pyridine Derivatives with Potential Anti-psychotic Activity, Eur. J. Med. Chem., 124, 456 (2016); https://doi.org/10.1016/j.ejmech.2016.08.059
W. An, W. Wang, T. Yu, Y. Zhang, Z. Miao, T. Meng and J. Shen, Discovery of Novel 2-Phenyl-imidazo[1,2-a]pyridine Analogues Targeting Tubulin Polymerization as Antiproliferative Agents, Eur. J. Med. Chem., 112, 367 (2016); https://doi.org/10.1016/j.ejmech.2016.02.004
B. Jadhav, R. Kenny, Y. Nivid, M. Mandewale and R. Yamgar, Synthesis and Evaluation of Antituberculosis Activity of Substituted 2,7-Dimethylimidazo[1,2-a]pyridine-3-Carboxamide Derivatives, Open J. Med. Chem., 6, 59 (2016); https://doi.org/10.4236/ojmc.2016.64006
S. Hemasrilatha, K. Sruthi, A. Manjula and V.H. Babu, Synthesis and Anti-Inflammatory Activity of Imidazo[1,2-a]pyridinyl/Pyrazinyl Benzamides and Acetamides, Indian J. Chem., 51B, 981 (2012).
W. Xhiqing, P. Yinyin and Z. Xiangge, Synthesis of 3-Arylimidazo[1,2-a]pyridines by a Catalyst-Free Cascade Process, Synthesis, 2011, 2255 (2011); https://doi.org/10.1055/s-0030-1260669
F. Goktas, N. Cesur, D. Satana and M. Uzun, Synthesis of Novel Imidazo[1,2-a]pyridines and Evaluation of their Antifungal Activities, Turk. J. Chem., 38, 581 (2014); https://doi.org/10.3906/kim-1307-14
T.H. Al-Tel, R.A. Al-Qawasmeh and R. Zaarour, Design, Synthesis and in vitro Antimicrobial Evaluation of Novel Imidazo[1,2 a]pyridine and Imidazo[2,1-b][1,3]benzothiazole Motifs, Eur. J. Med. Chem., 46, 1874 (2011); https://doi.org/10.1016/j.ejmech.2011.02.051
S. Marhadour, P. Marchand, F. Pagniez, M.-A. Bazin, C. Picot, O. Lozach, S. Ruchaud, M. Antoine, L. Meijer, N. Rachidi and P. Le Pape, Synthesis and Biological Evaluation of 2,3-diarylimidazo[1,2-a]-pyridines as Antileishmanial Agents, Eur. J. Med. Chem., 58, 543 (2012); https://doi.org/10.1016/j.ejmech.2012.10.048
A.J. Stasyuk, M. Banasiewicz, M.K. Cyranski and D.T. Gryko, Imidazo[1,2-a]pyridines Susceptible to Excited State Intramolecular Proton Transfer: One-Pot Synthesis via an Ortoleva-King Reaction, J. Org. Chem., 77, 5552 (2012); https://doi.org/10.1021/jo300643w
L. Cai, F.T. Chin, V.W. Pike, H. Toyama, J.S. Liow, S.S. Zoghbi, K. Modell, E. Briard, H.U. Shetty, K. Sinclair, S. Donohue, D. Tipre, M.P. Kung, C. Dagostin, D.A. Widdowson, M. Green, W. Gao, M.M. Herman, M. Ichise and R.B. Innis, Synthesis and Evaluation of Two 18F-Labeled 6-Iodo-2-(4¢-N,N-dimethylamino)phenylimidazo[1,2-a]-pyridine Derivatives as Prospective Radioligands for b-Amyloid in Alzheimer's Disease, J. Med. Chem., 47, 2208 (2004); https://doi.org/10.1021/jm030477w
Y. Zhang, Z. Chen, W. Wu, Y. Zhang and W. Su, CuI-Catalyzed Aerobic Oxidative a-Aminaton Cyclization of Ketones to Access Aryl or Alkenyl-Substituted Imidazoheterocycles, J. Org. Chem., 78, 12494 (2013); https://doi.org/10.1021/jo402134x
I.I. Roslan, K.-H. Ng, J.-E. Wu, G.-K. Chuah and S. Jaenicke, Synthesis of Disubstituted 3-Phenylimidazo[1,2-a]pyridines via 2-Aminopyridine/CBrCl3 a-Bromination Shuttle, J. Org. Chem., 81, 9167 (2016); https://doi.org/10.1021/acs.joc.6b01714
X. Han, C. Ma, Z. Wu and G. Huang, Zinc Iodide Catalyzed Synthesis of 3-Aminoimidazo[1,2-a]pyridines from 2-Aminopyridines and a-Amino Carbonyl Compounds, Synthesis, 48, 351 (2016); https://doi.org/10.1055/s-0035-1560375
A.L. Rousseau, P. Matlaba and C.J. Parkinson, Multicomponent Synthesis of Imidazo[1,2-a]pyridines using Catalytic Zinc Chloride, Tetrahedron Lett., 48, 4079 (2007); https://doi.org/10.1016/j.tetlet.2007.04.008
A.L. Krasovsky, V.G. Nenajdenko and E.S. Balenkova, A Facile Access to 2-CF3-Imidazo[1,2-a]pyridines, Synthesis, 1379 (2002); https://doi.org/10.1055/s-2002-33106
Z.-H. Ren, Z.-H. Guan, M.-N. Zhao, Y. Yi and Y.-Y. Wang, Copper-Catalyzed Aerobic Oxidative Cyclization of Ketoxime Acetates with Pyridines for the Synthesis of Imidazo[1,2-a]pyridines, Synthesis, 48, 1920 (2016); https://doi.org/10.1055/s-0035-1561950
R. Yan, G. Huang, H. Yan, S. Yang, X. Gao, K. Zhou and C. Ma, Iron(II)-Catalyzed Denitration Reaction: Synthesis of 3-Methyl-2-arylimidazo-[1,2-a]pyridine Derivatives from Aminopyridines and 2-Methylnitro-olefins, Synlett, 23, 2961 (2012); https://doi.org/10.1055/s-0032-1317685
S.K. Guchhait, A.L. Chandgude and G. Priyadarshani, CuSO4-Glucose for in situ Generation of Controlled Cu(I)-Cu(II) Bicatalysts: Multi-component Reaction of Heterocyclic Azine and Aldehyde with Alkyne and Cycloisomerization toward Synthesis of N-Fused Imidazoles, J. Org. Chem., 77, 4438 (2012); https://doi.org/10.1021/jo3003024
Y. Wang, B. Frett and H.-Y. Li, Efficient Access to 2,3-Diarylimidazo-[1,2-a]pyridines via a One-Pot, Ligand-Free, Palladium-Catalyzed Three-Component Reaction under Microwave Irradiation, Org. Lett., 16, 3016 (2014); https://doi.org/10.1021/ol501136e
M. Adib, H. Bijanzadeh, A. Mohamadi, E. Sheikhi and S. Ansari, Microwave-Assisted, One-Pot Reaction of Pyridines, a-Bromoketones and Ammonium Acetate: An Efficient and Simple Synthesis of Imidazo[1,2-a]pyridines, Synlett, 1606 (2010); https://doi.org/10.1055/s-0029-1219962
K.C. Chunawala, G. Joshi, E. Suresh and S. Adimurthy, Thermal and Microwave-Assisted Rapid Syntheses of Substituted Imidazo[1,2-a]-pyridines Under Solvent- and Catalyst-Free Conditions, Synthesis, 635 (2011); https://doi.org/10.1055/s-0030-1258405
B.S. Santaniello, M.J. Price and J.K. Murray Jr., Synthesis and Characterization of 2-Phenylimidazo[1,2-a]pyridine: A Privileged Structure for Medicinal Chemistry, J. Chem. Educ., 94, 388 (2017); https://doi.org/10.1021/acs.jchemed.6b00286
C.A. Winter, E.A. Risley and W.G. Nuss, Carrageenin-Induced Edema in Hind Paw of the Rat as an Assay for Antiinflammatory Drugs, Proc. Soc. Exp. Biol. Med., 111, 544 (1962); https://doi.org/10.3181/00379727-111-27849
C.H. Collins, Microbiological Mthods, Butterworth: London, p. 364 (1967).
R.J. Cruikshank, P. Durgid and R.R. Swain, Medical Microbiology, Churchill: Livingstone, vol. 1 (1998).