Login Register Cart 0
Generic placeholder image

Current Organic Synthesis

Editor-in-Chief

ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Letter Article

Polyethylene Glycol-400 Prompted an Efficient Synthesis of Thienyl Pyrazolo[ 1,5‐a] Pyrimidines as Microbial Inhibitors

Author(s): Shankaraiah G. Konda*, Santosh S. Chobe, Amit Kumar N. Gosar, Baliram S. Hote, and Gajanan G. Mandawad*

Volume 19, Issue 6, 2022

Published on: 20 May, 2022

Page: [693 - 701] Pages: 9

DOI: 10.2174/1570179419666220304160938

Price: $65

Abstract

Aims: The aim of this present work was to design and establish an efficient synthesis of new thienyl pyrazolo[1,5‐a] pyrimidines using an environmentally friendly reaction solvent. Further, the newly synthesized compounds were evaluated for antimicrobial activity.

Materials and Methods: A series of thienyl pyrazolo[1,5‐a] pyrimidines have been synthesized by the condensation reaction of 4‐(4’‐chloro‐phenylazo)‐5‐amino pyrazole with α, β‐ unsaturated carbonyl composites (chalcones) using NaOH in polyethylene glycol- 400 as a green reaction solvent. The dissemination technique recommended by the National Clinical Laboratory Standards Committee was used to study the antimicrobial activities of synthesized compounds.

Results and Discussion: Polyethylene glycol-400 prompting an efficient synthesis of thienyl pyrazolo[1,5‐a] pyrimidines have been discussed. Excellent yields of the products were obtained in a shorter reaction time using PEG 400 as a green reaction solvent. The reaction solvent was recovered and reused without the loss of its activity. The synthesized compounds have shown interesting antibacterial activity. Hydroxyl and halo substitution with thienyl moiety emerged as an active antibacterial and antifungal study.

Conclusion: The advantage of this methodology is that it incorporates the green method, has excellent yields, easy workup, avoids toxic solvents, and an expensive catalyst. The new dimension pyrazolo[1,5-a] pyrimidine derivatives with thienyl moiety exhibit promising anti-microbial activity.

Keywords: Green synthesis, polyethylene glycol-400, chalcones, 5-amino pyrazole, pyrazolo [1, 5-a]pyrimidines, antimicrobial activity.

« Previous Next »
Graphical Abstract

[1]
Castillo, J.C.; Portilla, J. Recent advances in the synthesis of new pyrazole derivatives. Targets Heterocycl. Syst, 2018, 22, 194-223.
[2]
Bakavoli, M.; Bagherzadeh, G.; Vaseghifar, M.; Shiri, A.; Pordel, M.; Mashreghi, M.; Pordeli, P.; Araghi, M. Molecular iodine promoted synthesis of new pyrazolo[3,4-d]pyrimidine derivatives as potential antibacterial agents. Eur. J. Med. Chem., 2010, 45(2), 647-650.
[http://dx.doi.org/10.1016/j.ejmech.2009.10.051] [PMID: 19926175]
[3]
Raffa, D.; Maggio, B.; Plescia, F.; Cascioferro, S.; Raimondi, M.V.; Plescia, S.; Cusimano, M.G. Pyrazolo[3,4-d]pyrimidine derivatives as COX-2 selective inhibitors: Synthesis and molecular modelling studies. Arch. Pharm. (Weinheim), 2009, 342(6), 321-326.
[http://dx.doi.org/10.1002/ardp.200800140] [PMID: 19479756]
[4]
Almansa, C.; de Arriba, A.F.; Cavalcanti, F.L.; Gómez, L.A.; Miralles, A.; Merlos, M.; García-Rafanell, J.; Forn, J. Synthesis and SAR of a new series of COX-2-selective inhibitors: Pyrazolo[1,5-a]pyrimidines. J. Med. Chem., 2001, 44(3), 350-361.
[http://dx.doi.org/10.1021/jm0009383] [PMID: 11462976]
[5]
el-Bendary, E.R.; Badria, F.A. Synthesis, DNA-binding, and antiviral activity of certain pyrazolo[3,4-d]pyrimidine derivatives. Arch. Pharm. (Weinheim), 2000, 333(4), 99-103.
[http://dx.doi.org/10.1002/(SICI)1521-4184(20004)333:4<99::AID-ARDP99>3.0.CO;2-O] [PMID: 10816902]
[6]
Chern, J.H.; Shia, K.S.; Hsu, T.A.; Tai, C.L.; Lee, C.C.; Lee, Y.C.; Chang, C.S.; Tseng, S.N.; Shih, S.R. Design, synthesis, and structure-activity relationships of pyrazolo[3,4-d]pyrimidines: A novel class of potent enterovirus inhibitors. Bioorg. Med. Chem. Lett., 2004, 14(10), 2519-2525.
[http://dx.doi.org/10.1016/j.bmcl.2004.02.092] [PMID: 15109643]
[7]
Oliveira-Campos, A.M.F.; Sivasubramanian, A.; Rodrigues, L.M.; Seijas, J.A.; Pilar Vázquez-Tato, M.; Peixoto, F.; Abreu, C.G.; Cidade, H.; Oliveira, A.E.; Pinto, M. Substituted pyrazolo[3,4-d]pyrimidines: Microwave-assisted, solvent-free synthesis and biological evaluation. Helv. Chim. Acta, 2008, 91(7), 1336-1345.
[http://dx.doi.org/10.1002/hlca.200890145]
[8]
Tang, J.; Wang, B.; Wu, T.; Wan, J.; Tu, Z.; Njire, M.; Wan, B.; Franzblauc, S.G.; Zhang, T.; Lu, X.; Ding, K. Design, synthesis, and biological evaluation of pyrazolo[1,5-a]pyridine-3-carboxamides as novel antitubercular agents. ACS Med. Chem. Lett., 2015, 6(7), 814-818.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00176] [PMID: 26191372]
[9]
Kiessling, A.; Wiesinger, R.; Sperl, B.; Berg, T. Selective inhibition of c-Myc/Max dimerization by a pyrazolo[1,5-a]pyrimidine. ChemMedChem, 2007, 2(5), 627-630.
[http://dx.doi.org/10.1002/cmdc.200600294] [PMID: 17315254]
[10]
Asano, T.; Yamazaki, H.; Kasahara, C.; Kubota, H.; Kontani, T.; Harayama, Y.; Ohno, K.; Mizuhara, H.; Yokomoto, M.; Misumi, K.; Kinoshita, T.; Ohta, M.; Takeuchi, M. Identification, synthesis, and biological evaluation of 6-[(6R)-2-(4-fluorophenyl)-6-(hydroxyl-methyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl]-2-(2-methylphenyl)pyridazin-3(2H)-one (AS1940477), a potent p38 MAP kinase inhibitor. J. Med. Chem., 2012, 55(17), 7772-7785.
[http://dx.doi.org/10.1021/jm3008008] [PMID: 22905713]
[11]
Hwang, J.Y.; Windisch, M.P.; Jo, S.; Kim, K.; Kong, S.; Kim, H.C.; Kim, S.; Kim, H.; Lee, M.E.; Kim, Y.; Choi, J.; Park, D.S.; Park, E.; Kwon, J.; Nam, J.; Ahn, S.; Cechetto, J.; Kim, J.; Liuzzi, M.; No, Z.; Lee, J. Discovery and characterization of a novel 7-aminopy-razolo[1,5-a]pyrimidine analog as a potent hepatitis C virus inhibitor. Bioorg. Med. Chem. Lett., 2012, 22(24), 7297-7301.
[http://dx.doi.org/10.1016/j.bmcl.2012.10.123] [PMID: 23159569]
[12]
Zhao, M.; Ren, H.; Chang, J.; Zhang, D.; Yang, Y.; He, Y.; Qi, C.; Zhang, H. Design and synthesis of novel pyrazolo[1,5-a]pyrimidine derivatives bearing nitrogen mustard moiety and evaluation of their antitumor activity in vitro and in vivo. Eur. J. Med. Chem., 2016, 119, 183-196.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.068] [PMID: 27162123]
[13]
Ghorab, M.M.; Ragab, F.A.; Alqasoumi, S.I.; Alafeefy, A.M.; Aboulmagd, S.A. Synthesis of some new pyrazolo[3,4-d]pyrimidine derivatives of expected anticancer and radioprotective activity. Eur. J. Med. Chem., 2010, 45(1), 171-178.
[http://dx.doi.org/10.1016/j.ejmech.2009.09.039] [PMID: 19853327]
[14]
Ramsey, S.J.; Attkins, N.J.; Fish, R.; van der Graaf, P.H. Quantitative pharmacological analysis of antagonist binding kinetics at CRF1 receptors in vitro and in vivo. Br. J. Pharmacol., 2011, 164(3), 992-1007.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01390.x] [PMID: 21449919]
[15]
Petroski, R.E.; Pomeroy, J.E.; Das, R.; Bowman, H.; Yang, W.; Chen, A.P.; Foster, A.C. Indiplon is a high-affinity positive allosteric modulator with selectivity for α1 subunit-containing GABAA receptors. J. Pharmacol. Exp. Ther., 2006, 317(1), 369-377.
[http://dx.doi.org/10.1124/jpet.105.096701] [PMID: 16399882]
[16]
Elie, R.; Rüther, E.; Farr, I.; Emilien, G.; Salinas, E. Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel non-benzodiazepine hypnotic. J. Clin. Psychiatry, 1999, 60(8), 536-544.
[http://dx.doi.org/10.4088/JCP.v60n0806] [PMID: 10485636]
[17]
Selleri, S.; Bruni, F.; Costagli, C.; Costanzo, A.; Guerrini, G.; Ciciani, G.; Gratteri, P.; Besnard, F.; Costa, B.; Montali, M.; Martini, C.; Fohlin, J.; De Siena, G.; Aiello, P.M. A novel selective GABA(A) α1 receptor agonist displaying sedative and anxiolytic-like properties in rodents. J. Med. Chem., 2005, 48(21), 6756-6760.
[http://dx.doi.org/10.1021/jm058002n] [PMID: 16220991]
[18]
Salem, M.A.; Helal, M.H.; Gouda, M.A. Abd EL-Gawad, H.H.; Shehab, M.A.M.; El-Khalafawy, A. Recent synthetic methodologies for pyrazolo[1,5-a]pyrimidine. Synth. Commun., 2019, 49(14), 1750-1776.
[http://dx.doi.org/10.1080/00397911.2019.1604967]
[19]
Al-Azmi, A. Pyrazolo[1,5-a]pyrimidines: A close look into their synthesis and applications. Curr. Org. Chem., 2019, 23(6), 721-743.
[http://dx.doi.org/10.2174/1385272823666190410145238]
[20]
Cherukupalli, S.; Karpoormath, R.; Chandrasekaran, B.; Hampannavar, G.A.; Thapliyal, N.; Palakollu, V.N. An insight on synthetic and medicinal aspects of pyrazolo[1,5-a]pyrimidine scaffold. Eur. J. Med. Chem., 2017, 126, 298-352.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.019] [PMID: 27894044]
[21]
Eftekhari-Sis, B.; Zirak, M. Chemistry of α-oxoesters: A powerful tool for the synthesis of heterocycles. Chem. Rev., 2015, 115(1), 151-264.
[http://dx.doi.org/10.1021/cr5004216] [PMID: 25423283]
[22]
Abu Elmaati, T.M.; El-Taweel, F.M. New trends in the chemistry of 5-Aminopyrazoles. J. Heterocycl. Chem., 2004, 41(2), 109-134.
[http://dx.doi.org/10.1002/jhet.5570410201]
[23]
Fraley, M.E.; Hoffman, W.F.; Rubino, R.S.; Hungate, R.W.; Tebben, A.J.; Rutledge, R.Z.; McFall, R.C.; Huckle, W.R.; Kendall, R.L.; Coll, K.E.; Thomas, K.A. Synthesis and initial SAR studies of 3,6-disubstituted pyrazolo[1,5-a]pyrimidines: A new class of KDR kinase inhibi-tors. Bioorg. Med. Chem. Lett., 2002, 12(19), 2767-2770.
[http://dx.doi.org/10.1016/S0960-894X(02)00525-5] [PMID: 12217372]
[24]
Anastas, P.T.; Warner, J.C. Principles of green chemistry. Theory Pract., 1998, 29.
[25]
Chen, J.; Spear, S.K.; Huddleston, J.G.; Rogers, R.D. Polyethylene glycol and solutions of polyethylene glycol as green reaction media. Green Chem., 2005, 7(2), 64-82.
[http://dx.doi.org/10.1039/b413546f]
[26]
Dawane, B.S.; Konda, S.G.; Mandawad, G.G.; Shaikh, B.M. Poly(ethylene glycol) (PEG-400) as an alternative reaction solvent for the synthesis of some new 1-(4-(4′-chlorophenyl)-2-thiazolyl)-3-aryl-5-(2-butyl-4-chloro-1H-imidazol-5yl)-2-pyrazolines and their in vitro anti-microbial evaluation. Eur. J. Med. Chem., 2010, 45(1), 387-392.
[http://dx.doi.org/10.1016/j.ejmech.2009.10.015] [PMID: 19896247]
[27]
Jorapur, Y.R.; Rajagopal, G.; Saikia, P.J.; Pal, R.R. Poly(ethylene glycol) (PEG) as an efficient and recyclable reaction medium for the synthesis of dibenz[b,f]-1,4-oxazepine. Tetrahedron Lett., 2008, 49(9), 1495-1497.
[http://dx.doi.org/10.1016/j.tetlet.2007.12.115]
[28]
Das, B.; Krishnaiah, M.; Balasubramanyam, P.; Veeranjaneyulu, B.; Nandankumar, D. A remarkably simple N-formylation of anilines using polyethylene glycol. Tet. Lett, 2008, 49, 2225-2227.
[29]
National Committee for Clinical Laboratory Standards Villanova (PA), NCCLS; 1998. (Publication No: NCCLS M 100-58).
[30]
Konda, S.G.; Humne, V.T.; Lokhande, P.D. Rapid and selective deallylation of allyl ethers and esters using iodine in polyethylene glycol-400. Green Chem., 2011, 13(9), 2354-2358.
[http://dx.doi.org/10.1039/c1gc15153c]
[31]
Konda, S.G. PEG-400: An efficient and recyclable reaction medium for the synthesis of pyrazolo [1, 5-a] pyrimidines. Eur. J. Chem., 2014, 5(4), 676-680.
[http://dx.doi.org/10.5155/eurjchem.5.4.676-680.1110]
[32]
Konda, S.G. Acetic acid in PEG-400: An efficient system for synthesis of 1-cinnamoyl-2-pyrazoline derivatives. J. Adv. Chem. Sci., 2016, 2(3), 363-365.
[33]
Mandawad, G.G.; Shaikh, B.M.; Chobe, S.S.; Konda, S.G. NaOH/PEG-400: An eloquent system for the synthesis of new thienyl benzo[b]1,4-diazepines. Eur. J. Chem., 2020, 11(4), 276-279.
[http://dx.doi.org/10.5155/eurjchem.11.4.276-279.2009]
[34]
Mandawad, G.G.; Chobe, S.S.; Yemul, O.S.; Dawane, B.S. An efficient green synthesis of some novel hetero chalcones as potent antimicrobial agents. J. Pharm. Res., 2011, 4(10), 3360-3363.
[35]
Krystof, V.; Cankar, P.; Frysová, I.; Slouka, J.; Kontopidis, G.; Dzubák, P.; Hajdúch, M.; Srovnal, J.; de Azevedo, W.F., Jr; Orság, M.; Paprskárová, M.; Rolcík, J.; Látr, A.; Fischer, P.M.; Strnad, M. 4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. J. Med. Chem., 2006, 49(22), 6500-6509.
[http://dx.doi.org/10.1021/jm0605740] [PMID: 17064068]
[36]
El- Gaby, M.S.A.; Sayed, A.Z.; Abu-Shanab, F.A.; Hessein, A.M. Studies on the synthesis of some pyrazolo[1,5-a]pyrimidines bearing sulfonamido moieties. Phosphorus Sulfur Silicon Relat. Elem., 2000, 164, 1-10.
[http://dx.doi.org/10.1080/10426500008045228]

Rights & Permissions Print Cite
Article Metrics
19
1
© 2024 Bentham Science Publishers | Privacy Policy