Synthesis Strategies and Medicinal Value of Pyrrole and its Fused
Heterocyclic Compounds

Samar   Said   Fatahala; Mosaad   Sayed   Mohamed; Jaqueline   Youssef   Sabry; Yara Esam   El-Deen   Mansour
Abstract

In the last several decades, interest in pyrrole and pyrrolopyrimidine derivatives has increased owing to their biological importance, such as anti-tumor, anti-microbial, anti-inflammatory, anti-diabetic, anti-histaminic, anti-malarial, anti-Parkinson, antioxidant and anti-viral effects, specially recently against COVID-19. These tremendous biological features have motivated scientists to discover more pyrrole and fused pyrrole derivatives, owing to the great importance of the pyrrole nucleus as a pharmacophore in many drugs, and motivated us to present this article, highlighting on the different synthetic pathways of pyrrole and its fused compounds, specially pyrrolopyrimidine, as well as their medicinal value from 2017 till 2021.
Keywords: Pyrrole, pyrrolopyrimidine, fused pyrrole, fused pyrrolopyrimidine, synthesis, medicinal value.
Graphical Abstract

[1] 
Sultan, S. Kasim.; Faazil, S.; S, A. A Grape juice catalyzed synthesis of substituted pyrrole by Paal-Knorr reaction. Int. J. Res. Cult. Soc.,  2018, 2(5), 31-35.
[2] 
Scott, J.S.; Degorce, S.L.; Anjum, R.; Culshaw, J.; Davies, R.D.M.; Davies, N.L.; Dillman, K.S.; Dowling, J.E.; Drew, L.; Ferguson, A.D.; Groombridge, S.D.; Halsall, C.T.; Hudson, J.A.; Lamont, S.; Lindsay, N.A.; Marden, S.K.; Mayo, M.F.; Pease, J.E.; Perkins, D.R.; Pink, J.H.; Robb, G.R.; Rosen, A.; Shen, M.; McWhirter, C.; Wu, D. Discovery and optimization of pyrrolopyrimidine inhibitors of interleukin-1 receptor associated kinase 4 (IRAK4) for the treatment of mutant MYD88L265P diffuse large B-cell lymphoma. J. Med. Chem.,  2017, 60(24), 10071-10091.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01290] [PMID:  29172502] 
[3] 
McGeary, R.P.; Tan, D.T.C.; Selleck, C.; Monteiro Pedroso, M.; Sidjabat, H.E.; Schenk, G. Structure-activity relationship study and optimisation of 2-aminopyrrole-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile as a broad spectrum metallo-β-lactamase inhibitor. Eur. J. Med. Chem.,  2017, 137, 351-364.
[http://dx.doi.org/10.1016/j.ejmech.2017.05.061] [PMID:  28614759] 
[4] 
El-Serwy, W.S.; El-Serwy, W.S.; Mohamed, N.A.; Kassem, E.M.M.; Mostafa, R.E.; Mohamed, H.S. Synthesis, biological evaluation, molecular docking, ADME predictions and QSAR studies of novel 1,2-diazet and pyrrole derivatives as anti-inflammatory agents. Russ. J. Bioorganic Chem.,  2021, 47(1), 183-198.
[http://dx.doi.org/10.1134/S1068162021010040] 
[5] 
Sroor, F.M.; Basyouni, W.M.; Tohamy, W.M.; Abdelhafez, T.H.; El-awady, M.K. Novel pyrrolo[2,3-d]pyrimidine derivatives: Design, synthesis, structure elucidation and in vitro anti-BVDV activity. Tetrahedron,  2019, 75(51), 130749.
[http://dx.doi.org/10.1016/j.tet.2019.130749] 
[6] 
Lee, J. C.; Bae, Y. H.; Chang, S.-K. Bulletin of the korean chemical
society efficient a-halogenation of carbonyl compounds by
nbromosuccinimide and N-chlorosuccinimde. Number 4 BKCSDE,  2003, 24(4), 407-408.
[7] 
Katouah, H.A.; Gaffer, H.E. Synthesis and docking study of pyrimidine derivatives scaffold for anti-hypertension application. ChemistrySelect,  2019, 4(20), 6250-6255.
[http://dx.doi.org/10.1002/slct.201900799] 
[8] 
Khalil, O.M.; Kamal, A.M.; Bua, S.; El Sayed Teba, H.; Nissan, Y.M.; Supuran, C.T. Pyrrolo and pyrrolopyrimidine sulfonamides act as cytotoxic agents in hypoxia via inhibition of transmembrane carbonic anhydrases. Eur. J. Med. Chem.,  2020, 188, 112021.
[http://dx.doi.org/10.1016/j.ejmech.2019.112021] [PMID:  31901743] 
[9] 
Samzadeh-Kermani, A.; Ghasemi, S. A catalytic route to pyrrole derivatives via copper-catalyzed multicomponent reaction. J. Heterocycl. Chem.,  2019, 56(8), 2202-2209.
[http://dx.doi.org/10.1002/jhet.3614] 
[10] 
Fairoosa, J.; Neetha, M.; Anilkumar, G. Recent developments and perspectives in the copper-catalyzed multicomponent synthesis of heterocycles. RSC Advances,  2021, 11(6), 3452-3469.
[http://dx.doi.org/10.1039/D0RA10472H] 
[11] 
Aksu, K.; Özgeriş, B.; Tümer, F. Synthesis and characterization of new N-substituted 2- aminopyrrole derivatives. Org. Commun.,  2019, 12(1), 38-42.
[http://dx.doi.org/10.25135/acg.oc.55.19.03.1222] 
[12] 
Tümer, F.; Ekinci, D.; Zilbeyaz, K.; Demir, Ü. An efficient synthesis of substituted 4-aryl-3-cyano-2-amino thiophenes by a stepwise Gewald reaction. Turk. J. Chem.,  2004, 28(4), 395-403.
[13] 
Andreas, S.; Kalogirou, S. 2-Amino-5-chloro-1h-pyrrole-3,4-dicarbonitrile. Molbank,  2021, 1-4.
[14] 
Kuruba, B.K.; Shariff, N.; Vasanthkumar, S.; Emmanuvel, L. NaOH/Et 3N-promoted stereoselective one-pot synthesis of α-diazo oxime ethers via diazo transfer reaction. Synth. Commun.,  2015, 45(21), 2454-2461.
[http://dx.doi.org/10.1080/00397911.2015.1085575] 
[15] 
Kuruba, B.K.; Vasanthkumar, S.; Emmanuvel, L. Rhodium-catalyzed synthesis of 2,3 – disubstituted N-methoxy pyrroles and furans via [3+2] cycloaddition between metal carbenoids and activated olefins. Tetrahedron,  2017, 73(22), 3093-3098.
[http://dx.doi.org/10.1016/j.tet.2017.04.007] 
[16] 
Liu, Y.; Hu, H.; Wang, X.; Zhi, S.; Kan, Y.; Wang, C. Synthesis of pyrrole via a silver-catalyzed 1,3-dipolar cycloaddition/oxidative dehydrogenative aromatization tandem reaction. J. Org. Chem.,  2017, 82(8), 4194-4202.
[http://dx.doi.org/10.1021/acs.joc.7b00180] [PMID:  28326778] 
[17] 
Ma, Z.; Ma, Z.; Zhang, D. Synthesis of multi-substituted pyrrole derivatives through [3+2] cycloaddition with tosylmethyl isocyanides (tosmics) and electron-deficient compounds. Molecules,  2018, 23(10), E2666.
[http://dx.doi.org/10.3390/molecules23102666] [PMID:  30336556] 
[18] 
Walter, H.; Lamberth, C.; Corsi, C. Synthesis of fungicidally active succinate dehydrogenase inhibitors with novel difluoromethylated heterocyclic acid moieties. Monatsh. Chem.,  2018, 149(4), 791-799.
[http://dx.doi.org/10.1007/s00706-017-2101-y] 
[19] 
Arun Divakar, M.; Shanmugam, S. Live cell imaging of bacterial cells: Pyrenoylpyrrole-based fluorescence labeling. Chem. Biol. Drug Des.,  2017, 90(4), 554-560.
[http://dx.doi.org/10.1111/cbdd.12978] [PMID:  28303654] 
[20] 
Salehi, P.; Tanbakouchian, Z.; Farajinia-Lehi, N.; Shiri, M. Cascade synthesis of 2,4-disulfonylpyrroles by the sulfonylation/[2 + 3]-cycloaddition reactions ofgem-dibromoalkenes with arylsulfonyl methyl isocyanides. RSC Advances,  2021, 11(22), 13292-13296.
[http://dx.doi.org/10.1039/D0RA10451E] 
[21] 
Rasal, N.K.; Sonawane, R.B.; Jagtap, S.V. Potential 2,4-dimethyl-1H-pyrrole-3-carboxamide bearing benzimidazole template: Design, synthesis, in vitro anticancer and in silico ADME study. Bioorg. Chem.,  2020, 97, 103660.
[http://dx.doi.org/10.1016/j.bioorg.2020.103660] [PMID:  32086056] 
[22] 
Louroubi, A.; Hasnaoui, A.; Ait Aicha, Y.; Abdallah, N.; Idouhli, R.; Benyaich, A.; Ait Ali, M.; El Firdoussi, L. 3-Acetyl-2,5-dimethyl-1,4-diphenylpyrrole: Synthesis, X-ray structure, DFT, TDDFT studies and anti-corrosion activity. Chem. Data Collect.,  2021, 32, 100662.
[http://dx.doi.org/10.1016/j.cdc.2021.100662] 
[23] 
Leonardi, M.; Villacampa, M.; Menéndez, J.C. Mild and general synthesis of pyrrolo[2,1-a]isoquinolines and related polyheterocyclic frameworks from pyrrole precursors derived from a mechanochemical multicomponent reaction. J. Org. Chem.,  2017, 82(5), 2570-2578.
[http://dx.doi.org/10.1021/acs.joc.6b02995] [PMID:  28186415] 
[24] 
Leonardi, M.; Villacampa, M.; Menéndez, J.C. High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units. Beilstein J. Org. Chem.,  2017, 13, 1957-1962.
[http://dx.doi.org/10.3762/bjoc.13.190] [PMID:  29062414] 
[25] 
Gudi, Y.; Gundala, S.; Venkatapuram, P.; Adivireddy, P.; Chippada, A.R.; Allagadda, R. Synthesis and antioxidant activity of a new class of pyridinylcarbamoylmethyl pyrrolyl/pyrazolyl-carboxamides. J. Heterocycl. Chem.,  2017, 54(6), 3498-3509.
[http://dx.doi.org/10.1002/jhet.2973] 
[26] 
Hassani, M.; Naimi-Jamal, M.R.; Panahi, L. One-pot multicomponent synthesis of substituted pyrroles by using chitosan as an organocatalyst. ChemistrySelect,  2018, 3(2), 666-672.
[http://dx.doi.org/10.1002/slct.201702692] 
[27] 
Kishii, N.; Shimadu, M.; Maruyama, S.; Tou, S.; Sasaki, I.; Sugimura, H. Synthesis of polyfunctionalized pyrroles bearing C-2 α-azido side-chains and displacement of the α-azido group by various nucleophiles. Tetrahedron Lett.,  2018, 59(8), 776-780.
[http://dx.doi.org/10.1016/j.tetlet.2018.01.049] 
[28] 
Ram, R.N.; Sadanandan, S.; Kumar Gupta, D. β,β,β-trichloroethyl-NH-enamine as viable system for 5-endo-trig radical cyclization via multifaceted CuI−CuII redox catalysis: Single step synthesis of multi-functionalized NH-pyrroles. Adv. Synth. Catal.,  2019, 361(24), 5661-5676.
[http://dx.doi.org/10.1002/adsc.201900938] 
[29] 
Ahankar, H.; Ramazani, A.; Saeidian, H.; Ślepokura, K.; Lis, T. Synthesis, crystal structure, and DFT studies of ethyl 4-hydroxy-2-(4-methoxyphenyl)-5-oxo- 1-phenyl-2,5-dihydro-1h-pyrrole-3-carboxylate. J. Struct. Chem.,  2021, 62(1), 47-57.
[http://dx.doi.org/10.1134/S0022476621010066] 
[30] 
Wang, K.; Deng, Z.H.; Xie, S.J.; Zhai, D.D.; Fang, H.Y.; Shi, Z.J. Synthesis of arylamines and N-heterocycles by direct catalytic nitrogenation using N2. Nat. Commun.,  2021, 12(1), 248.
[http://dx.doi.org/10.1038/s41467-020-20270-5] [PMID:  33431885] 
[31] 
Karimi, S.; Ma, S.; Qu, M.; Chen, B.; Ramig, K.; Greer, E.M.; Szalda, D.J.; Neary, M.C.; Berkowitz, W.F.; Subramaniam, G. A new synthesis of biologically active pyrroles: Formal synthesis of pentabromopseudilin, bimetopyrol, and several antitubercular agents. J. Heterocycl. Chem.,  2020, 57(1), 327-336.
[http://dx.doi.org/10.1002/jhet.3780] 
[32] 
Guan, Z.R.; Liu, S.; Liu, Z.M.; Ding, M.W. One-pot three-component synthesis of pyrrolidin-2-ones via a sequential wittig/nucleophilic addition/cyclization reaction. Synthesis,  2019, 51(11), 2402-2408.
[http://dx.doi.org/10.1055/s-0037-1612279] 
[33] 
Shabalin, D.A.; Ushakov, I.A.; Kuzmin, A.V.; Vashchenko, A.V.; Yu., Schmidt E.; Trofimov, B. A site- and stereoselective synthesis of bridgehead tetrahydropyrrolo[2,3-c]pyridines from ketoximes and acetylene gas in two synthetic operations. Tetrahedron Lett.,  2020, 61(9), 151533.
[http://dx.doi.org/10.1016/j.tetlet.2019.151533] 
[34] 
Ishibashi, F.; Fukuda, T.; Zha, S.; Hashirano, A.; Hirao, S.; Iwao, M. Concise synthesis and in vitro anticancer activity of benzo[g][1]benzopyrano[4,3-b]indol-6(13H)-ones (BBPIs), topoisomerase I inhibitors based on the marine alkaloid lamellarin. Biosci. Biotechnol. Biochem.,  2021, 85(1), 181-191.
[http://dx.doi.org/10.1093/bbb/zbaa028] [PMID:  33577663] 
[35] 
Kizimova, I.A.; Igidov, N.M.; Kiselev, M.A.; Dmitriev, M.V.; Chashchina, S.V.; Siutkina, A.I. Synthesis of new 2-aminopyrrole derivatives by reaction of furan-2,3-diones 3-acylhydrazones with CH-nucleophiles. Russ. J. Gen. Chem.,  2020, 90(2), 182-186.
[http://dx.doi.org/10.1134/S1070363220020036] 
[36] 
Kharitonova, S.S.; Igidov, N.M.; Zakhmatov, A.V.; Rubtsov, A.E. Chemistry of iminofuran: VIII. Recyclization of 5-aryl-3-arylimino-3h- furan-2-ones effected by cyanoacetic acid derivatives. Russ. J. Org. Chem.,  2013, 49(2), 243-252.
[http://dx.doi.org/10.1134/S1070428013020115] 
[37] 
Kumar, P.; Kapur, M. Catalyst control in positional-selective C-H alkenylation of isoxazoles and a ruthenium-mediated assembly of trisubstituted pyrroles. Org. Lett.,  2019, 21(7), 2134-2138.
[http://dx.doi.org/10.1021/acs.orglett.9b00446] [PMID:  30860851] 
[38] 
Liu, H. The synthesis of pyrrole from C4-olefinated isoxazole catalyzed by ruthenium: A density functional theory study. J. Phys. Org. Chem.,  2021, 34(5), 3-6.
[http://dx.doi.org/10.1002/poc.4178] 
[39] 
Zykova, S.S.; Igidov, N.M.; Zakhmatov, A.V.; Kiselev, M.A.; Galembikova, A.R.; Khusnutdinov, R.R.; Dunaev, P.D.; Boichuk, S.V.; Chernov, I.N.; Rodin, I.A. Synthesis and biological activity of 2-amino-1-aryl-5-(3,3-dimethyl-2-oxobutylidene)-4-oxo-n-(thiazol-5-yl)-4,5-dihydro-1h-pyrrole-3-carboxamides. Pharm. Chem. J.,  2018, 52(3), 198-204.
[http://dx.doi.org/10.1007/s11094-018-1790-9] 
[40] 
Abdelbaset, M.S.; Abdelrahman, M.H.; Bukhari, S.N.A.; Gouda, A.M.; Youssif, B.G.M.; Abdel-Aziz, M.; Abuo-Rahma, G.E.A. Design, synthesis, and biological evaluation of new series of pyrrol-2(3H)-one and pyridazin-3(2H)-one derivatives as tubulin polymerization inhibitors. Bioorg. Chem.,  2021, 107, 104522.
[http://dx.doi.org/10.1016/j.bioorg.2020.104522] [PMID:  33317838] 
[41] 
Romagnoli, R.; Oliva, P.; Salvador, M.K.; Manfredini, S.; Padroni, C.; Brancale, A.; Ferla, S.; Hamel, E.; Ronca, R.; Maccarinelli, F.; Rruga, F.; Mariotto, E.; Viola, G.; Bortolozzi, R. A facile synthesis of diaryl pyrroles led to the discovery of potent colchicine site antimitotic agents. Eur. J. Med. Chem.,  2021, 214, 113229.
[http://dx.doi.org/10.1016/j.ejmech.2021.113229] [PMID:  33550186] 
[42] 
Wang, G.M.; Wang, X.; Zhu, J.M.; Guo, B. Bin; Yang, Z.; Xu, Z. J.; Li, B.; Wang, H. Y.; Meng, L. H.; Zhu, W. L.; Ding, J. Docking-based structural splicing and reassembly strategy to develop novel deazapurine derivatives as potent B-Raf V600E inhibitors. Acta Pharmacol. Sin.,  2017, 38(7), 1059-1068.
[http://dx.doi.org/10.1038/aps.2016.173] [PMID:  28414204] 
[43] 
Karamthulla, S.; Jana, A.; Choudhury, L.H. Synthesis of novel 5,6-disubstituted pyrrolo [2,3-d]pyrimidine-2,4-diones via one-pot three-component reactions. ACS Comb. Sci.,  2017, 19(2), 108-112.
[http://dx.doi.org/10.1021/acscombsci.6b00147] [PMID:  28036166] 
[44] 
Yadav, V.B.; Rai, P.; Sagir, H.; Kumar, A.; Siddiqui, I.R. A green route for the synthesis of pyrrolo[2,3-d] pyrimidine derivatives catalyzed by β-cyclodextrin. New J. Chem.,  2018, 42(1), 628-633.
[http://dx.doi.org/10.1039/C7NJ03577B] 
[45] 
Lee, J.H.; Shin, S.C.; Seo, S.H.; Seo, Y.H.; Jeong, N.; Kim, C.W.; Kim, E.E.K.; Keum, G. Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3-d]pyrimidines as potent Hsp90 inhibitors. Bioorg. Med. Chem. Lett.,  2017, 27(2), 237-241.
[http://dx.doi.org/10.1016/j.bmcl.2016.11.062] [PMID:  27914802] 
[46] 
Musumeci, F.; Fallacara, A.L.; Brullo, C.; Grossi, G.; Botta, L.; Calandro, P.; Chiariello, M.; Kissova, M.; Crespan, E.; Maga, G.; Schenone, S. Identification of new pyrrolo[2,3-d]pyrimidines as Src tyrosine kinase inhibitors in vitro active against Glioblastoma. Eur. J. Med. Chem.,  2017, 127(127), 369-378.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.036] [PMID:  28076826] 
[47] 
Saroha, M.; Khanna, G.; Khurana, J.M. Synthesis of novel 5-substituted 6-phenylpyrrolo[2, 3-d]pyrimidine derivatives via one-pot three-component reactions under catalyst-free condition. ChemistrySelect,  2017, 2(24), 7263-7266.
[http://dx.doi.org/10.1002/slct.201701234] 
[48] 
Wang, L.; Zheng, L.; Kong, X.; Zhang, W.; Chen, G.; Wang, J. Concise synthesis of pyrrolo[2,3-d]pyrimidine derivatives via the Cu-catalyzed coupling reaction. Green Chem. Lett. Rev.,  2017, 10(1), 42-47.
[http://dx.doi.org/10.1080/17518253.2016.1275822] 
[49] 
Balaraman, S.; Nayak, N.; Subbiah, M.; Elango, K.P. Synthesis and antiviral study of novel 4-(2-(6-amino-4-oxo-4,5-dihydro-1h-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives. Med. Chem. Res.,  2018, 27(11–12), 2538-2546.
[http://dx.doi.org/10.1007/s00044-018-2256-z] 
[50] 
Barnett, C.J.; Wilson, T.M.; Kobierski, M.E. A practical synthesis of multitargeted antifolate LY231514. Org. Process Res. Dev.,  1999, 3(3), 184-188.
[http://dx.doi.org/10.1021/op9802172] 
[51] 
Bayat, M.; Nasri, S. Synthesis and dynamic 1H NMR study of pyrazolo substituted pyrrolo[2,3-d]pyrimidines via a regioselective heterocyclization. J. Mol. Struct.,  2018, 1154, 366-372.
[http://dx.doi.org/10.1016/j.molstruc.2017.10.056] 
[52] 
Cawrse, B.M.; Lapidus, R.S.; Cooper, B.; Choi, E.Y.; Seley-Radtke, K.L. Anticancer properties of halogenated pyrrolo[3,2-d]pyrimidines with decreased toxicity via N5 substitution. ChemMedChem,  2018, 13(2), 178-185.
[http://dx.doi.org/10.1002/cmdc.201700641] [PMID:  29193845] 
[53] 
Temburnikar, K.W.; Ross, C.R.; Wilson, G.M.; Balzarini, J.; Cawrse, B.M.; Seley-Radtke, K.L. Antiproliferative activities of halogenated pyrrolo[3,2-d]pyrimidines. Bioorg. Med. Chem.,  2015, 23(15), 4354-4363.
[http://dx.doi.org/10.1016/j.bmc.2015.06.025] [PMID:  26122770] 
[54] 
Javahershenas, R.; Khalafy, J. One-pot, three-component synthesis of pyrrolo. Pyrimidine Derivatives.,  2018, 62, 1-9.
[55] 
Gill, C.H.; Chate, A.V.; Shinde, G.Y.; Sarkate, A.P.; Tiwari, S.V. One-pot, four-component synthesis and SAR studies of spiro[pyrimido[5,4-b]quinoline-10,5′-pyrrolo[2,3-d]pyrimidine] derivatives catalyzed by β-cyclodextrin in water as potential anticancer agents. Res. Chem. Intermed.,  2018, 44(7), 4029-4043.
[http://dx.doi.org/10.1007/s11164-018-3353-9] 
[56] 
Ahmadi Sabegh, M.; Khalafy, J.; Etivand, N. One-Pot, three-component synthesis of a series of new bis-pyrrolo[2,3-d]pyrimidines in the presence of TPAB under reflux conditions. J. Heterocycl. Chem.,  2018, 55(11), 2610-2618.
[http://dx.doi.org/10.1002/jhet.3320] 
[57] 
Lee, J.H.; El-Damasy, A.K.; Seo, S.H.; Gadhe, C.G.; Pae, A.N.; Jeong, N.; Hong, S.S.; Keum, G. Novel 5,6-disubstituted pyrrolo[2,3-d]pyrimidine derivatives as broad spectrum antiproliferative agents: Synthesis, cell based assays, kinase profile and molecular docking study. Bioorg. Med. Chem.,  2018, 26(21), 5596-5611.
[http://dx.doi.org/10.1016/j.bmc.2018.10.004] [PMID:  30385226] 
[58] 
Gao, T.; Zhang, C.; Shi, X.; Guo, R.; Zhang, K.; Gu, J.; Li, L.; Li, S.; Zheng, Q.; Cui, M.; Cui, M.; Gao, X.; Liu, Y.; Wang, L. Targeting dihydrofolate reductase: Design, synthesis and biological evaluation of novel 6-substituted pyrrolo[2,3-d]pyrimidines as nonclassical antifolates and as potential antitumor agents. Eur. J. Med. Chem.,  2019, 178, 329-340.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.013] [PMID:  31200235] 
[59] 
Kilic-Kurt, Z.; Aka, Y.; Kutuk, O. Novel pyrrolopyrimidine derivatives induce p53-independent apoptosis via the mitochondrial pathway in colon cancer cells. Chem. Biol. Interact.,  2020, 330(April), 109236.
[http://dx.doi.org/10.1016/j.cbi.2020.109236] [PMID:  32866467] 
[60] 
Park, A.; Choi, S.M.; Kim, T.S.; Yum, E.K. Microwave-assisted synthesis of 5,6,7-trisubstituted pyrrolo[2,3-d]pyrimidines via palladium-catalyzed heteroannulation with internal alkynes. Bull. Korean Chem. Soc.,  2019, 40(11), 1134-1137.
[http://dx.doi.org/10.1002/bkcs.11866] 
[61] 
Chung, S.H.; Park, J.; Lee, J.W.; Song, J.; Jung, D.; Min, K.H. Structure-activity relationship of 7-aryl-2-anilino-pyrrolopyrimidines as Mer and Axl tyrosine kinase inhibitors. J. Enzyme Inhib. Med. Chem.,  2020, 35(1), 1822-1833.
[http://dx.doi.org/10.1080/14756366.2020.1825407] [PMID:  32972253] 
[62] 
Fathinezhad, M. AbbasiTarighat, M.; Dastan, D. Chemometrics heavy metal content clusters using electrochemical data of modified carbon paste electrode. Environ. Nanotechnol. Monit. Manag.,  2020, 14(April), 100307.
[http://dx.doi.org/10.1016/j.enmm.2020.100307] 
[63] 
Mohammadizadeh, M.R.; Bahramzadeh, M.; Taghavi, S.Z. A novel one-pot and efficient procedure for the synthesis of 3h-spiro[isobenzofuran-1,6′-pyrrolo[2,3-d]pyrimidine]-2′,3,4′, 5′-tetraones. Tetrahedron Lett.,  2010, 51(44), 5807-5809.
[http://dx.doi.org/10.1016/j.tetlet.2010.08.113] 
[64] 
Mousa, B.A.; Bayoumi, A.H.; Korraa, M.M.; Assy, M.G.; El-Kalyoubi, S.A. A novel one-pot and efficient procedure for synthesis of new fused uracil derivatives for DNA binding. Int. J. Org. Chem. (Irvine),  2015, 05(01), 37-47.
[http://dx.doi.org/10.4236/ijoc.2015.51005] 
[65] 
Zhang, Y.L.; Xu, C.T.; Liu, T.; Zhu, Y.; Luo, Y. An improved synthesis of 4-chloro-7h-pyrrolo[2,3-d]pyrimidine. Chem. Heterocycl. Compd.,  2018, 54(6), 638-642.
[http://dx.doi.org/10.1007/s10593-018-2320-0] 
[66] 
Selvakumar, B.; Elango, K.P. Synthesis of non-glutamate-type pyrrolo[2,3-d]pyrimidines via direct aminocarbonylation of aryl halides using solid CO2(co)8 as a co source and their antibacterial activity. J. Chem. Res.,  2017, 41(4), 230-234.
[http://dx.doi.org/10.3184/174751917X14894997017658] 
[67] 
Schmitt, S.M.; Stefan, K.; Wiese, M. Pyrrolopyrimidine derivatives and purine analogs as novel activators of Multidrug Resistance-associated Protein 1 (MRP1, ABCC1). Biochim. Biophys. Acta Biomembr.,  2017, 1859(1), 69-79.
[http://dx.doi.org/10.1016/j.bbamem.2016.10.017] [PMID:  27810353] 
[68] 
Stefan, K.; Schmitt, S.M.; Wiese, M. 9-Deazapurines as broad-spectrum inhibitors of the ABC transport proteins p-glycoprotein, multidrug resistance-associated protein 1, and breast cancer resistance protein. J. Med. Chem.,  2017, 60(21), 8758-8780.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00788] [PMID:  29016119] 
[69] 
Tian, C.; Wang, M.; Han, Z.; Fang, F.; Zhang, Z.; Wang, X.; Liu, J. Design, synthesis and biological evaluation of novel 6-substituted pyrrolo [3,2-d] pyrimidine analogues as antifolate antitumor agents. Eur. J. Med. Chem.,  2017, 138, 630-643.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.002] [PMID:  28711701] 
[70] 
Adel, M.; Serya, R.A.T.; Lasheen, D.S.; Abouzid, K.A.M. Identification of new pyrrolo[2,3-d]pyrimidines as potent VEGFR-2 tyrosine kinase inhibitors: Design, synthesis, biological evaluation and molecular modeling. Bioorg. Chem.,  2018, 81, 612-629.
[http://dx.doi.org/10.1016/j.bioorg.2018.09.001] [PMID:  30248512] 
[71] 
Ettehadi, Z.; Davoodnia, A.; Khashi, M.; Ali Beyramabadi, S. Tautomerism in the sulfonamide moiety: Synthesis, experimental and theoretical characterizations. J. Struct. Chem.,  2018, 59(7), 1596-1609.
[http://dx.doi.org/10.1134/S0022476618070119] 
[72] 
Dong, X.; Tang, J.; Hu, C.; Bai, J.; Ding, H.; Xiao, Q. An expeditious total synthesis of 5′-deoxy-toyocamycin and 5′-deoxysangivamycin. Molecules,  2019, 24(4), 1-9.
[http://dx.doi.org/10.3390/molecules24040737] [PMID:  30791372] 
[73] 
Golani, L.K.; Islam, F.; O’Connor, C.; Dekhne, A.S.; Hou, Z.; Matherly, L.H.; Gangjee, A. Design, synthesis and biological evaluation of novel pyrrolo[2,3-d]pyrimidine as tumor-targeting agents with selectivity for tumor uptake by high affinity folate receptors over the reduced folate carrier. Bioorg. Med. Chem.,  2020, 28(12), 115544.
[http://dx.doi.org/10.1016/j.bmc.2020.115544] [PMID:  32503687] 
[74] 
Fischer, T.; Krüger, T.; Najjar, A.; Totzke, F.; Schächtele, C.; Sippl, W.; Ritter, C.; Hilgeroth, A. Discovery of novel substituted benzo-anellated 4-benzylamino pyrrolopyrimidines as dual EGFR and VEGFR2 inhibitors. Bioorg. Med. Chem. Lett.,  2017, 27(12), 2708-2712.
[http://dx.doi.org/10.1016/j.bmcl.2017.04.053] [PMID:  28478927] 
[75] 
Veselovská, L.; Pohl, R.; Tloušt Ová, E.; Gurská, S.; Džubák, P.; Hajdúch, M.; Hocek, M. Pyrido-fused deazapurine bases: Synthesis and glycosylation of 4-substituted 9H-pyrido[2′,3′:4,5]- and pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidines. ACS Omega,  2020, 5(40), 26278-26286.
[http://dx.doi.org/10.1021/acsomega.0c04302] [PMID:  33073155] 
[76] 
Veselovská, L.; Kudlová, N.; Gurská, S.; Lišková, B.; Medvedíková, M.; Hodek, O.; Tloušťová, E.; Milisavljevic, N.; Tichý, M.; Perlíková, P.; Mertlíková-Kaiserová, H.; Trylčová, J.; Pohl, R.; Klepetářová, B.; Džubák, P.; Hajdúch, M.; Hocek, M. Synthesis and cytotoxic and antiviral activity profiling of all-four isomeric series of pyrido-fused 7-deazapurine ribonucleosides. Chemistry,  2020, 26(57), 13002-13015.
[http://dx.doi.org/10.1002/chem.202001124] [PMID:  32275109] 
[77] 
Fleuti, M.; Bártová, K.; Slavětínská, L.P.; Tloušt’ová, E.; Tichý, M.; Gurská, S.; Pavliš, P.; Džubák, P.; Hajdúch, M.; Hocek, M. Synthesis and biological profiling of pyrazolo-fused 7-deazapurine nucleosides. J. Org. Chem.,  2020, 85(16), 10539-10551.
[http://dx.doi.org/10.1021/acs.joc.0c00928] [PMID:  32692916] 
[78] 
Tokarenko, A.; Lišková, B.; Smoleń, S.; Táborská, N.; Tichý, M.; Gurská, S.; Perlíková, P.; Frydrych, I.; Tloušt’ová, E.; Znojek, P.; Mertlíková-Kaiserová, H.; Poštová Slavětínská, L.; Pohl, R.; Klepetářová, B.; Khalid, N.U.; Wenren, Y.; Laposa, R.R.; Džubák, P.; Hajdúch, M.; Hocek, M. Synthesis and cytotoxic and antiviral profiling of pyrrolo- and furo-fused 7-deazapurine ribonucleosides. J. Med. Chem.,  2018, 61(20), 9347-9359.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01258] [PMID:  30281308] 
[79] 
Ghosh, K.; Perlíková, P.; Havlíček, V.; Yang, C.; Pohl, R.; Tloušťová, E.; Hodek, J.; Gurská, S.; Džubák, P.; Hajdúch, M.; Hocek, M. Isomeric naphtho-fused 7-deazapurine nucleosides and nucleotides: Synthesis, biological activity, photophysical properties and enzymatic incorporation to nucleic acids. Eur. J. Org. Chem.,  2018, 2018(37), 5092-5108.
[http://dx.doi.org/10.1002/ejoc.201800165] 
[80] 
Kondo, Y. Ryo WATANABE, T. S.; Y, H Condensed heteroaromatic ring systems. XVI. Synthesis of pyrrolo[2,3-d]pyrimidine derivatives. Chem. Pharm. Bull. (Tokyo),  1989, 37(11), 2933-2936.
[http://dx.doi.org/10.1248/cpb.37.2933] 
[81] 
Tichý, M.; Smoleń, S.; Deingruber, T.; Džubák, P.; Pohl, R.; Slavětínská, L.P.; Hajdúch, M.; Hocek, M. Thienopyrrolo[2, 3-d]pyrimidines, new tricyclic nucleobase analogues: Synthesis and biological activities. ChemistrySelect,  2018, 3(31), 9144-9149.
[http://dx.doi.org/10.1002/slct.201802190] 
[82] 
Mosrin, M.; Knochel, P. Regio- and chemoselective metalation of chloropyrimidine derivatives with TMPMgCl x LiCl and TMP(2)Zn x 2 MgCl(2) x 2 LiCl. Chemistry,  2009, 15(6), 1468-1477.
[http://dx.doi.org/10.1002/chem.200801831] [PMID:  19115285] 
[83] 
Fatahala, S.S.; Khedr, M.A.; Mohamed, M.S. Synthesis and structure activity relationship of some indole derivatives as potential anti-inflammatory agents. Acta Chim. Slov.,  2017, 64(4), 865-876.
[http://dx.doi.org/10.17344/acsi.2017.3481] [PMID:  29318292] 
[84] 
Fatahala, S.S.; Mohamed, M.S.; Youns, M.; Abd-El Hameed, R.H. Synthesis and evaluation of cytotoxic activity of some pyrroles and fused pyrroles. Anticancer. Agents Med. Chem.,  2017, 17(7), 1014-1025.
[http://dx.doi.org/10.2174/1871520617666170102152928] [PMID:  28042776] 
[85] 
Said Fatahala, S.; Hasabelnaby, S.; Goudah, A.; Mahmoud, G.I.; Helmy Abd-El Hameed, R.; Muñoz-Torrero, D. Pyrrole and fused pyrrole compounds with bioactivity against inflammatory mediators. Molecules,  2017, 22(3), 1-18.
[http://dx.doi.org/10.3390/molecules22030461] [PMID:  28304349] 
[86] 
Zheng, G.Z.; Lee, C.; Pratt, J.K.; Perner, R.J.; Jiang, M.Q.; Gomtsyan, A.; Matulenko, M.A.; Mao, Y.; Koenig, J.R.; Kim, K.H.; Muchmore, S.; Yu, H.; Kohlhaas, K.; Alexander, K.M.; McGaraughty, S.; Chu, K.L.; Wismer, C.T.; Mikusa, J.; Jarvis, M.F.; Marsh, K.; Kowaluk, E.A.; Bhagwat, S.S.; Stewart, A.O. Pyridopyrimidine analogues as novel adenosine kinase inhibitors. Bioorg. Med. Chem. Lett.,  2001, 11(16), 2071-2074.
[http://dx.doi.org/10.1016/S0960-894X(01)00375-4] [PMID:  11514141] 
[87] 
Rashad, A.E.; Sayed, H.H.; Shamroukh, A.H.; Awad, H.M. Preparation of some fused pyridopyrimidine and pyridothienotriazine derivatives for biological evaluation. Phosphorus Sulfur Silicon Relat. Elem.,  2005, 180(12), 2767-2777.
[http://dx.doi.org/10.1080/104265090968118] 
[88] 
Domínguez-Villa, F.X.; Durán-Iturbide, N.A.; Ávila-Zárraga, J.G. Synthesis, molecular docking, and in silico adme/tox profiling studies of new 1-aryl-5-(3-azidopropyl)indol-4-ones: Potential inhibitors of SARS CoV-2 main protease. Bioorg. Chem.,  2020, 2021, 106.
[http://dx.doi.org/10.1016/j.bioorg.2020.104497] [PMID:  33261847] 
[89] 
Mcdonald, B.G.; Proctor, G.R.; Chemistry, A. Conversion of 2-chloroallylamines into heterocyclic compounds.part 1. 2-methylindoles, 1,5,6,7-tetrahydro-3-methylindol-4-ones, and related heterocycles. J. Chem. Soc., Perkin Trans. 1,  1975, (24), 3537-3733.
[90] 
Borra, S.; Chandrasekhar, D.; Newar, U.D.; Maurya, R.A. Access to 2,3-fused pyrroles via visible light driven coupling of α-azidochalcones with 1/2-naphthols, or 2-hydroxy-1,4-naphthoquinone. J. Org. Chem.,  2019, 84(2), 1042-1052.
[http://dx.doi.org/10.1021/acs.joc.8b02459] [PMID:  30547589] 
[91] 
Fakhar, Z.; Khan, S.; AlOmar, S.Y.; Alkhuriji, A.; Ahmad, A. ABBV-744 as a potential inhibitor of SARS-CoV-2 main protease enzyme against COVID-19. Sci. Rep.,  2021, 11(1), 234.
[http://dx.doi.org/10.1038/s41598-020-79918-3] [PMID:  33420186] 
[92] 
Liu, Y.; Zhang, Z.; Ran, F.; Guo, K.; Chen, X.; Zhao, G. Extensive investigation of benzylic N-containing substituents on the pyrrolopyrimidine skeleton as Akt inhibitors with potent anticancer activity. Bioorg. Chem.,  2020, 97(February), 103671.
[http://dx.doi.org/10.1016/j.bioorg.2020.103671] [PMID:  32120074] 
[93] 
Li, P.; Ge, X.; Wu, H.L. Crystal structure, anti-cervical cancer activity and docking studies of a new heterocycles compound. Main Group Chem.,  2019, 18(2), 63-70.
[http://dx.doi.org/10.3233/MGC-180680] 
[94] 
Wang, X.; Yu, C.; Wang, C.; Ma, Y.; Wang, T.; Li, Y.; Huang, Z.; Zhou, M.; Sun, P.; Zheng, J.; Yang, S.; Fan, Y.; Xiang, R. Novel cyclin-dependent kinase 9 (CDK9) inhibitor with suppression of cancer stemness activity against non-small-cell lung cancer. Eur. J. Med. Chem.,  2019, 181, 111535.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.038] [PMID:  31376566] 
[95] 
Tsai, P.Y.; Hu, G.S.; Huang, P.H.; Jheng, H.L.; Lan, C.H.; Chen, Y.S.; Chang, J.M.; Chuang, S.H.; Huang, J.J. Design, synthesis, and in vitro/vivo anticancer activity of 4-substituted 7-(3-fluoro-4-methoxybenzyl)-7h-pyrrolo[2,3-d]pyrimidines. J. Chin. Chem. Soc. (Taipei),  2021, 68(March), 1-10.
[http://dx.doi.org/10.1002/jccs.202100100] 
[96] 
Wang, L.; Liu, X.; Duan, Y.; Li, X.; Zhao, B.; Wang, C.; Xiao, Z.; Zheng, P.; Tang, Q.; Zhu, W. Discovery of novel pyrrolopyrimidine/pyrazolopyrimidine derivatives bearing 1,2,3-triazole moiety as c-Met kinase inhibitors. Chem. Biol. Drug Des.,  2018, 92(1), 1301-1314.
[http://dx.doi.org/10.1111/cbdd.13192] [PMID:  29575727] 
[97] 
Song, X.; Liu, X.; Ding, X. Staurosporine scaffold-based rational discovery of the wild-type sparing reversible inhibitors of EGFR T790M gatekeeper mutant in lung cancer with analog-sensitive kinase technology. J. Mol. Recognit.,  2017, 30(4), 1-11.
[http://dx.doi.org/10.1002/jmr.2590] [PMID:  27891677] 
[98] 
Zhang, X.; Zhang, J.; Liu, F. 7-H-pyrrolo[2,3-d]pyrimidine derivative
acts as promising agent for gastric cancer treatment by inducing
cell death. 3 Biotech.,  2019, 9(11), 3-10.
[http://dx.doi.org/10.1007/s13205-019-1937-8] 
[99] 
Redzicka, A.; Czyżnikowska, Ż.; Wiatrak, B.; Gębczak, K.; Kochel, A. Design and synthesis of N-substituted 3,4-pyrroledicarboximides as potential anti-inflammatory agents. Int. J. Mol. Sci.,  2021, 22(3), 1-21.
[http://dx.doi.org/10.3390/ijms22031410] [PMID:  33573356] 
[100] 
Amblard, F.; Boucle, S.; Bassit, L.; Chen, Z.; Sari, O.; Cox, B.; Verma, K.; Ozturk, T.; Ollinger-Russell, O.; Schinazi, R.F. Discovery and structure activity relationship of glyoxamide derivatives as anti-hepatitis B virus agents. Bioorg. Med. Chem.,  2021, 31(31), 115952.
[http://dx.doi.org/10.1016/j.bmc.2020.115952] [PMID:  33421915] 
[101] 
Messore, A.; Corona, A.; Madia, V.N.; Saccoliti, F.; Tudino, V.; De Leo, A.; Scipione, L.; De Vita, D.; Amendola, G.; Di Maro, S.; Novellino, E.; Cosconati, S.; Métifiot, M.; Andreola, M.L.; Valenti, P.; Esposito, F.; Grandi, N.; Tramontano, E.; Costi, R.; Di Santo, R. Pyrrolyl pyrazoles as non-diketo acid inhibitors of the HIV-1 ribonuclease H function of reverse transcriptase. ACS Med. Chem. Lett.,  2020, 11(5), 798-805.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00617] [PMID:  32435387] 
[102] 
Li, Q.; Groaz, E.; Rocha-Pereira, J.; Neyts, J.; Herdewijn, P. Anti-norovirus activity of C7-modified 4-amino-pyrrolo[2,1-f][1,2,4] triazine C-nucleosides. Eur. J. Med. Chem.,  2020, 195, 112198.
[http://dx.doi.org/10.1016/j.ejmech.2020.112198] [PMID:  32294613] 
[103] 
Mallikarjuna Reddy, G.; Camilo, A., Jr; Raul Garcia, J. Pyrrole-2,5-dione analogs as a promising antioxidant agents: Microwave-assisted synthesis, bio-evaluation, SAR analysis and DFT studies/interpretation. Bioorg. Chem.,  2021, 106, 104465.
[http://dx.doi.org/10.1016/j.bioorg.2020.104465] [PMID:  33229119] 
[104] 
Zykova, S.S.; Danchuk, M.S.; Talismanov, V.S.; Tokareva, N.G.; Igidov, N.M.; Rodin, I.A.; Koshchaev, A.G.; Gugushvili, N.N.; Karmanova, O.G. Predictive and experimental determination of antioxidant activity in the series of substituted 4-(2,2-dimethylpropanoyl)-3-hydroxy-1,5-diphenyl-1,5-dihydro-2h-pyrrol-2-ones. J. Pharm. Sci. Res.,  2018, 10(1), 164-166.
[105] 
Hussain, H.; Abbas, G.; Green, I.R.; Ali, I. Dipeptidyl peptidase IV inhibitors as a potential target for diabetes: Patent review (2015-2018). Expert Opin. Ther. Pat.,  2019, 29(7), 535-553.
[http://dx.doi.org/10.1080/13543776.2019.1632290] [PMID:  31203700] 
[106] 
Xie, H.; Zeng, S.; He, Y.; Zhang, G.; Yu, P.; Zhong, G.; Xu, H.; Yang, L.; Wang, S.; Zhao, X.; Hu, W. Rapid generation of a novel DPP-4 inhibitor with long-acting properties: SAR study and PK/PD evaluation. Eur. J. Med. Chem.,  2017, 141, 519-529.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.029] [PMID:  29078995] 
[107] 
Nishio, Y.; Kimura, H.; Tosaki, S.; Sugaru, E.; Sakai, M.; Horiguchi, M.; Masui, Y.; Ono, M.; Nakagawa, T.; Nakahira, H. Discovery of new chemotype dipeptidyl peptidase IV inhibitors having (R)-3-amino-3-methyl piperidine as a pharmacophore. Bioorg. Med. Chem. Lett.,  2010, 20(24), 7246-7249.
[http://dx.doi.org/10.1016/j.bmcl.2010.10.101] [PMID:  21074430] 
[108] 
Zhang, Z.; Wallace, M.B.; Feng, J.; Stafford, J.A.; Skene, R.J.; Shi, L.; Lee, B.; Aertgeerts, K.; Jennings, A.; Xu, R.; Kassel, D.B.; Kaldor, S.W.; Navre, M.; Webb, D.R.; Gwaltney, S.L. II Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV. J. Med. Chem.,  2011, 54(2), 510-524.
[http://dx.doi.org/10.1021/jm101016w] [PMID:  21186796] 
[109] 
Ding, X.; Stasi, L.P.; Ho, M.H.; Zhao, B.; Wang, H.; Long, K.; Xu, Q.; Sang, Y.; Sun, C.; Hu, H.; Yu, H.; Wan, Z.; Wang, L.; Edge, C.; Liu, Q.; Li, Y.; Dong, K.; Guan, X.; Tattersall, F.D.; Reith, A.D.; Ren, F. Discovery of 4-ethoxy-7H-pyrrolo[2,3-d]pyrimidin-2-amines as potent, selective and orally bioavailable LRRK2 inhibitors. Bioorg. Med. Chem. Lett.,  2018, 28(9), 1615-1620.
[http://dx.doi.org/10.1016/j.bmcl.2018.03.045] [PMID:  29588215] 
[110] 
Christensen, K.V.; Smith, G.P.; Williamson, D.S. Development of LRRK2 inhibitors for the treatment of Parkinson’s disease. Prog. Med. Chem.,  2017, 56, 37-80.
[http://dx.doi.org/10.1016/bs.pmch.2016.11.002] 
[111] 
Khanal, P. Remdesivir for COVID-19 treatment: Mechanism of action, synthesis, and clinical trials. World J. Pharm. Pharm. Sci.,  2020, 9(July), 1062-1068.
[http://dx.doi.org/10.20959/wjpps20208-16808] 
[112] 
Lins, R.L.; Matthys, K.E.; Verpooten, G.A.; Peeters, P.C.; Dratwa, M.; Stolear, J.C.; Lameire, N.H. Pharmacokinetics of atorvastatin and its metabolites after single and multiple dosing in hypercholesterolaemic haemodialysis patients. Nephrol. Dial. Transplant.,  2003, 18(5), 967-976.
[http://dx.doi.org/10.1093/ndt/gfg048] [PMID:  12686673] 
[113] 
Mena, A.C.; Pulido, E.G.; Guillén-Ponce, C. Understanding the molecular-based mechanism of action of the tyrosine kinase inhibitor. Sunitinib. Anticancer Drugs,  2010, 21(Suppl. 1), S3-S11.
[http://dx.doi.org/10.1097/01.cad.0000361534.44052.c5] [PMID:  20110785] 
[114] 
Wild, M.J.; McKillop, D.; Butters, C.J. Determination of the human cytochrome P450 isoforms involved in the metabolism of zolmitriptan. Xenobiotica,  1999, 29(8), 847-857.
[http://dx.doi.org/10.1080/004982599238290] [PMID:  10553725] 
[115] 
Roila, F.; Del Favero, A. Ondansetron clinical pharmacokinetics. Clin. Pharmacokinet.,  1995, 29(2), 95-109.
[http://dx.doi.org/10.2165/00003088-199529020-00004] [PMID:  7586904] 
[116] 
Brocks, D.R.; Jamali, F. Clinical pharmacokinetics of ketorolac tromethamine. Clin. Pharmacokinet.,  1992, 23(6), 415-427.
[http://dx.doi.org/10.2165/00003088-199223060-00003] [PMID:  1458761] 
[117] 
Olsen, J.; Li, C.; Skonberg, C.; Bjørnsdottir, I.; Sidenius, U.; Benet, L.Z.; Hansen, S.H. Studies on the metabolism of tolmetin to the chemically reactive acyl-coenzyme A thioester intermediate in rats. Drug Metab. Dispos.,  2007, 35(5), 758-764.
[http://dx.doi.org/10.1124/dmd.106.013334] [PMID:  17303625] 
[118] 
Baumann, M.; Baxendale, I.R.; Ley, S.V.; Nikbin, N. An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals. Beilstein J. Org. Chem.,  2011, 7, 442-495.
[http://dx.doi.org/10.3762/bjoc.7.57] [PMID:  21647262] 
[119] 
Siva Prasad, A.; Mohonty, S.; Satyanarayana, B. A cost effective and large-scale synthesis of zolmitriptan: An anti-migrane drug. Der Pharma Chem.,  2012, 4(1), 347-351.
Cite As
Medicinal Chemistry

Synthesis Strategies and Medicinal Value of Pyrrole and its Fused Heterocyclic Compounds

Abstract

Graphical Abstract
