Author(s): Y.E. Matiichuk, M.I. Sulyma, T.I. Chaban, V.V. Ogurtsov, V. S. Matiychuk


DOI: 10.5958/0974-360X.2020.01017.3   

Address: Y.E. Matiichuk1, M.I. Sulyma1, T.I. Chaban1*, V.V. Ogurtsov1, V. S. Matiychuk2
1Department of General, Bioinorganic, Physical and Colloidal Chemistry, Danylo Halytsky Lviv National Medical University, 69 Pekarska, Lviv, 79010, Ukraine.
2Department of Organic Chemistry, Ivan Franko National University of Lviv, 6 Kyryla and Mefodia, Lviv, 79005, Ukraine.
*Corresponding Author

Published In:   Volume - 13,      Issue - 12,     Year - 2020

By the reaction of furan-2-carboxylic acids with diazonium salts 1a-e the arylfuran-2-carboxylic acids 3a-e were synthesized. Acids 3a-e were transformed into appropriated acylchlorides 4a-e and were used for preparation of N-(R1-phenyl)-5-(R-phenyl)-2-furamides 6a-k. The structures of target compounds 6a-k were confirmed by using 1H NMR spectroscopy and elemental analysis. The compounds 6d-f with high antimicrobial activity against C. Neoformans ATCC 208821 were identified. It also have been found that compound 6i to be high active and against PC-3 Prostate Cancer cell lines (GP = 34.42) and 6f SR Leukemia cell lines (GP = 59.81).

Cite this article:
Y.E. Matiichuk, M.I. Sulyma, T.I. Chaban, V.V. Ogurtsov, V. S. Matiychuk. Synthesis and Biological evolution N-(R1-phenyl)-5-(R-phenyl)-2-furamides. Research J. Pharm. and Tech. 2020; 13(12):5837-5843. doi: 10.5958/0974-360X.2020.01017.3

1.    Indorkar D, Chourasia OP, Limaye SN. Synthesis, characterization, and some metal complexes incorporating 4- chlorobenzaldimine 4- aminoantipyrine and 2-aminophenol in antimicrobial activity. Asian Journal of Research in Chemistry.2015; 8 (3): 161-164. DOI: 10.5958/0974-4150.2015.00028.0.
2.    Rathore D, Sharma V. A Convenient, Rapid Microwave Assisted Synthesis of Some Novel Imidazole Derivatives and Their Antimicrobial Activity. Asian Journal of Research in Chemistry. 2016; 9 (10): 469-474. DOI: 10.5958/0974-4150.2016.00070.5.
3.    Shaikh AA, Raghuwanshi MG. Synthesis, Characterization of Some Novel Schiff’s bases of 4-((2-methyl-4/5-nitro-1H-imidazol-1-yl) methyl) thiazol-2-amine and their Antimicrobial Activity. Asian Journal of Research in Chemistry. 2016; 9 (11): 469-474. DOI: 10.5958/0974-4150.2016.00079.1.
4.    Singh K, Kumari S, Gupta Y. Synthesis and Antimicrobial Activity of Mono, Di and Tri Substituted Aromatic Amines and Napthyl Amine Cyclic Imides Derivatives. International Journal of Technology. 2017; 7 (2): 85-89. DOI: 10.5958/2231-3915.2017.00014.1.
5.    Choubey R, Choubey N, Garg G. Antimicrobial activity of newly Synthesized Pyrazolidine-3, 5-dione Substituted Thiochromene Derivatives. Research Journal of Pharmacy and Technology. 2015; 8 (9): 1250-1258. DOI: 10.5958/0974-360X.2015.00227.9.
6.    Pawar K, Kumbhar P, Shah V. Synthesis of Quinazoline derivatives and its Antimicrobial Activity. Research Journal of Pharmacy and Technology. 2017; 10 (8): 2611-2613. DOI: 10.5958/0974-360X.2017.00463.2.
7.    El-Sharkawy K, El-Brrati M, Ghardaly I, Ali M. Design and synthesis of thiazol derivatives with biological evaluations as antitumor agents. Research Journal of Pharmacy and Technology. 2015; 8 (5): 520-528. DOI: 10.5958/0974-360X.2017.00463.2.
8.    Ray N, Singh R, Singh J, Bhati S, Kaushik V. Computational screening of Thiohydantoin Derivatives for antitumor activity. Research Journal of Pharmacy and Technology. 2020; 13 (2): 795-800. DOI: 10.5958/0974-360X.2020.00150.X.
9.    Muppavarapu S, Bairam R. Synthesis, Characterization and Biological Evaluation of Some Novel Substituted 1, 3-Thaizine Derivatives. Research Journal of Pharmacy and Technology. 2017; 9 (1): 13-18. DOI: 10.5958/2321-5836.2017.00003.9.
10.    Alwin T, Abbs Fen Reji TF. Synthesis and antioxidant, antibacterial studies on 2-(2-arylaminothiazol-5-oyl) benzofurans. Asian J. Research Chem. 2017; 10 (6): 789-802. DOI: 10.5958/0974-4150.2017.00133.X.
11.    Bhalgat CM, Patil SL, Chitale SK, Randive K, Patil KG, Patil S. Synthesis and Cytotoxic Studies of Newer 3-(1-Benzofuran-2-Yl)-5-(Substituted Aryl) Isoxazole. Research Journal of Pharmacy and Technology. 2011; 4 (2): 247-251.
12.    Lunkad AS, Kothawade SN, Jadhav DV, Chaudhari PS, Bornare SP. Synthesis and Antimicrobial Activity of Some New Chalcones Containing Benzofuran and Benzofuran Schiff Bases. Research Journal of Pharmacy and Technology. 2015; 8 (3): 276-279. DOI: 10.5958/0974-360X.2015.00046.3.
13.    Ramesh V, Shantakumar SM, Bhagavanraju M. Synthesis and Evaluation of Some New Benzofuran Derivative for Antimicrobial Activity. Asian J. Research Chem. 2011; 4 (6): 1009-1013.
14.    Dahikar GD, Ramteke AN, Gadwe AA, Yeole PG. Synthesis and evaluation of antimicrobial activity of some 5-[(5-substituted furan-2-yl) methylene]-(3H)-3-substituted benzyl-4-thioxo thiazolidine-2-one derivatives. Asian J. Research Chem. 2012; 5 (7): 896-898.
15.    Arora M, Saravanan J, Mohan S, Bhattacharjee S. Synthesis, Characterization and Antimicrobial Activity of Some Schiff Bases of 2-amino-4-(4-chlorophenyl)–n-(3-furan-2-ylmethyl carboxamido) thiophenes. Asian J. Research Chem. 2013; 6 (1): 24-28.
16.    Lozynska L, Tymoshuk O, Chaban T. Spectrophotometric studies of 4-[n’-(4-imino-2-oxo-thiazolidin-5-ylidene)-hydrazino]-benzenesulfonic acid as a reagent for the determination of Palladium. Acta Chimica Slovenica. 2015; 62: 159-167. DOI:10.17344/acsi.2014.866.
17.    Singh N, Gupta RK. Synthesis of 2-acetylfuran by vapor phase acylation of furan over ferrite. Asian J. Research Chem. 2016; 9 (5): 200-204. DOI: 10.5958/0974-4150.2016.00034.1.
18.    Ayfan AK, Muslim RF, Noori NS. Preparation and Characterization of Novel disubstituted 1,3- Oxazepine-tetra-one from Schiff bases reaction with 3-methylfuran-2,5-dione and 3-Phenyldihydrofuran-2,5-dione. Research Journal of Pharmacy and Technology. 2019; 12 (3): 1008-1016. DOI: 10.5958/0974-360X.2019.00167.7.
19.    Ganatra SH, Gurjar SH. Structure-Based Studies of 2-Bezylidine-Benzofuran-3-One Class of Compounds as the Cyclin Dependent Kinases (CDKs) Inhibitor. Asian J. Research Chem. 2012; 5 (6): 712-717.
20.    Thorat BR, Nazirkar B, Thorat VB, More K, Jagtap R, Yamgar R. Synthesis, SAR, Molecular Docking and Anti-TB study of 3-Hydroxy-1-Benzofuran-2-Carbohydrazide. Asian J. Research Chem. 2016; 9 (3): 116-126. DOI: 10.5958/0974-4150.2016.00021.3.
21.    Hu QS, Wang Pe. Theoretical Study on the Mechanism of the Multi-Channel Reaction Between (2E,4E)-6-Hydroxyhexa-2,4-Dien-1-Ylium and Furan-2,5-Dione. Asian J. Research Chem. 2013; 6 (11): 1054-1059.
22.    Bhoot D, Khunt R, Parekh H. Synthesis and biological evaluation of chalcones and acetyl pyrazoline derivatives comprising furan nucleus as an antitubercular agents. Medicinal Chemistry Research. 2012; 21 (10): 3233-3239. DOI: 10.1007/s00044-011-9857-0.
23.    Fortuna CG, Barresi V, Berellini G, Musumarra G Design and synthesis of trans 2-(furan-2-yl)vinyl heteroaromatic iodides with antitumor activity. Bioorganic & Medicinal Chemistry. 2008; 16 (7): 4150-4159. DOI: 10.1016/j.bmc.2007.12.042
24.    Tarleton M, Gilbert J, Sakoff JA, McCluskey A. Cytotoxic 2-phenylacrylnitriles, the importance of the cyanide moiety and discovery of potent broad spectrum cytotoxic agents. European Journal of Medicinal Chemistry. 2012; 57: 65-73. DOI: 10.1016/j.ejmech.09.019.
25.    Wiesner J, Mitsch A, Jomaa H, Schlitzer M Structure-activity relationships of novel antimalarial agents. Part 7: N-(3-Benzoyltolylacetylaminophenyl)-3-(5-aryl-2-furyl) acrylic acid amides with polar moieties. Bioorganic & Medicinal Chemistry Letters. 2003; 13(13): 2159-2161. DOI: 10.1016/S0960-894X(03)00353-6.
26.    Shivarama B, Akberali PM, Shivananda MK Studies on nitrophenylfuran derivatives Part XII. Synthesis, characterization, antibacterial and antiviral activities of some nitrophenylfurfurylidene-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines. Farmaco. 2001; 56 (12): 919-927. DOI: 10.1016/S0014-827X(01)01124-7.
27.    Eisenmann M, Steuber H, Zentgraf |M, Altenkämper M, Ortmann R, Perruchon J, Klebe G, Schlitzer M. Structure-based optimization of aldose reductase inhibitors originating from virtual screening. ChemMedChem. 2009; 4 (5): 809-819. DOI: 10.1002/cmdc.200800410.
28.    Mitsch A, Wißner P, Silber K, Haebel P, Sattler I, Klebe G,Schlitzer M. Non-thiolfarnesyltransferase inhibitors: N-(4-tolylacetylamino-3-benzoylphenyl)-3-arylfurylacrylic acid amides. Bioorganic & Medicinal Chemistry. 2004; 12 (17): 4585-4600. DOI: 10.1016/j.bmc.2004.07.010.
29.    Pfefferkorn J, Greene M, Nugent R, Gross R, Mitchel M, Finzel C, Harris M, Wells P, Shelly J, Anstadt A, Kikuskie R, Kopta L, Schwende F. Inhibitors of HCVNS5B polymerase. Part 1: Evaluation of the southern region of (2Z)-2-(benzoylamino)-3-(5-phenyl-2-furyl) acrylic acid. Bioorganic & Medicinal Chemistry Letters. 2005; 15 (10): 2481-2486. DOI: 10.1016/j.bmcl.2005.03.066.
30.    Vazquez J, Tautz L, Ryan J, Vuori K, Mustelin T, Pellecchia M. Development of Molecular Probes for Second-Site Screening and Design of Protein Tyrosine Phosphatase Inhibitors. Journal of Medicinal Chemistry. 2007; 50 (9): 2137-2143. DOI: 10.1021/jm061481l.
31.    Haffner C, Lenhard J, Miller A, McDougald D, Dwornik K, Ittoop O, Gampe R, Xu H, Blanchard S, Montana V, Consler T, Bledsoe R, Ayscue A, Croom D. Structure-Based Design of Potent Retinoid X Receptor α Agonists. Journal of Medicinal Chemistry. 2004; 47 (8): 2010-2029. DOI: 10.1021/jm030565g.
32.    Van Veldhoven J, Blad C, Artsen C, Klopman C, Wolfram D, Abdelkadir M, Lanel R, Brusse J, Izerman A. Structure-activity relationships of trans-substituted-propenoic acid derivatives on thenicotinic acid receptor HCA2 (GPR109A). Bioorganic & Medicinal Chemistry Letters. 2011; 21 (9): 2736-2739. DOI: 10.1016/j.bmcl.2010.11.091.
33.    Guerrero M, Urbano M, Velaparth Si, Zhao J,Shaeffer M, Brown S, Rosen H, Roberts E. Discovery, design and synthesis of the first reported potent and selective sphingosine-1-phosphate 4(S1P4) receptor antagonists. Bioorganic & Medicinal Chemistry Letters. 2011; 21 (12): 3632-3636. DOI: 10.1016/j.bmcl.2011.04.097.
34.    Engers D, Field J, Le U, Zhou Y, Bolinger J, Zamorano R, Blobaum A, Jones C, Jadhav S, Weaver C, Conn P, Lindsley C, Niswender C, Hopkins C. Discovery, Synthesis, and Structure-Activity Relationship Development of a Series of N-(4 Acetamido) phenylpicolinamides as Positive Allosteric Modulators of Metabotropic Glutamate Receptor 4 (mGlu4) with CNS Exposure in Rats. Journal of Medicinal Chemistry. 2011; 54 (4): 1106-1110. DOI: 10.1021/jm101271s.
35.    Kleemann A, Engel J, Kutscher B, Reichert D. Pharmaceutical. 2001; substances: syntheses, patents, applications. 4th ed. Stuttgart, New York: Thieme, 2488 p.
36.    Obushak ND, GorakYuI, Matiichuk VS, Lytvyn RZ. Synthesis of heterocycles based on arylation products of unsaturated compounds: XVII. Arylation of 2-acetylfuran and synthesis of 3-R-6-(5-aryl-2-furyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines. Russian Journal of Organic Chemistry. 2008; 44 (11): 1689-1694. DOI: 10.1134/S1070428008110213.
37.    Gorak YuI, Obushak ND, Matiichuk VS, Lytvyn RZ. Synthesis of heterocycles from arylation products of unsaturated compounds: XVIII. 5-Arylfuran-2-carboxylic acids and their application in the synthesis of 1,2,4-thiadiazole, 1,3,4-oxadiazole and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives. Russian Journal of Organic Chemistry. 2009; 45 (4): 541-550. DOI: 10.1134/S1070428009040125.
38.    Obushak ND, Matiichuk VS, Vasylyshin RYa, Ostapyuk YuV. Heterocyclic syntheses on the basis of arylation products of unsaturated compounds: X. 3-aryl-2-chloropropanals as reagents for the synthesis of 2-amino-1,3-thiazole derivatives. Russian Journal of Organic Chemistry. 2004; 40 (3): 383-389. DOI: 10.1023/B: RUJO.0000034976.75646.85.
39.    Ostapiuk YV, Obushak MD, Matiychuk VS, Naskrent M, Gzella AK. A convenient method for the synthesis of 2-[(5-benzyl-1,3-thiazol-2-yl) imino]-1,3-thiazolidin-4-one derivatives. Tetrahedron Letters. 2012; 53 (5): 543-545. DOI: 10.1016/j.tetlet.2011.11.093.
40.    Pokhodylo NT, Savka RD, Matiichuk VS, Obushak ND. Synthesis and selected transformations of 1-(5-methyl-1-aryl-1H-1,2,3- triazol-4-yl)ethanonesand 1-[4-(4-R-5-methyl-1H-1,2,3-triazol-1-yl)phenyl] ethanones. Russian Journal of General Chemistry. 2009; 79 (2): 309-314. DOI: 10.1134/S1070363209020248.
41.    Chaban T, Klenina O, Drapak I, Ogurtsov V, Chaban I, Novikov V. Synthesis of some novel thiazolo[4,5-b]pyridines and their tuberculostatic activity evaluation. Chemistry and Chemical Technology. 2014; 89: 287-292.
42.    Chaban T, Klenina O, Harkov S, Ogurtsov V, Chaban I, Nektegaev I. Synthesis of some new N3 substituted 6-phenylazo-3Н-thiazolo[4,5-b]pyridin-2-ones as possible anti-inflammatory agents. Pharmacia. 2017; 64 (4): 16-30.
43.    Chaban T, Klenina O, Chaban I, Ogurtsov V, Harkov S, Lelyukh M. Thiazolo[5,4-d]pyrimidines and thiazolo[4,5-d] pyrimidines: A review on synthesis and Pharmacological importance of their derivatives. Pharmacia. 2018; 65 (2): 54-70.
44.    Chaban T, Matiychuk V, Ogurtsov V, Chaban I, Harkov S, Nektegaev I. Synthesis and biological activity of some novel derivatives 5,7-dimethyl-6-phenylazo-3Н-thiazolo[4,5-b]pyridine-2-one. Pharmacia. 2018; 65 (4): 51-62.
45.    Chaban TI, Ogurtsov VV, Matiychuk VS, Chaban IG, Demchuk IL, Nektegayev IA. Synthesis, anti-inflammatory and antioxidant activities of novel 3H-thiazolo[4,5-b]pyridines. Acta Chimica Slovenica. 2019; 66: 103–111. DOI: 10.17344/acsi.2018.4570.
46.    Chaban Z, Harkov S, Chaban T, Klenina O, Ogurtsov V, Chaban I. Recent advances in synthesis and biological activity evaluation of condensed thiazoloquinazolines: A review. Pharmacia. 2017; 64 (3): 52-66.
47.    Chaban T, Matiychuk V, Mahlovanyy A, Chaban I, Ogurtsov V, Lelyukh M. Antitumor properties of thiazolo[4,5-b]pyridin-2-one derivatives. Biointerface Research in Applied Chemistry. 2020; 10 (4): 5944-5950. DOI:10.33263/BRIAC104.944950.
48.    Chaban TI, Matiychuk VS, Ogurtsov VV, Chaban IG, Nektegayev IA. Development of effective anti-inflammatory drug candidates among novel thiazolopyridines. Ukrainian Biochemical Journal. 2020; 92 (2): 132-139.
49.    Klenina O, Chaban T, Zimenkovsky B, Harkov S, Ogurtsov V, Chaban I, Myrko I. Qsar modeling for antioxidant activity of novel N3 substituted 5,7-dimethyl-3Н-thiazolo[4,5-b]pyridin-2-ones. Pharmacia. 2017; 64 (4): 49-71.
50.    Lozynska L, Tymoshuk O, Chaban T. Spectrophotometric studies of 4-[n’-(4-imino-2-oxo-thiazolidin-5-ylidene)-hydrazino]-benzenesulfonic acid as a reagent for the determination of Palladium. Acta Chimica Slovenica. 2015; 62: 159-167. DOI: 10.17344/acsi.2014.866.
51.    Zubkov FI, Ershova JD, Zaytsev VP, Obushak MD, Matiychuk VS, Sokolova EA, Khrustalev VN, Varlamov AV. The first example of an intramolecular Diels-Alder furan (IMDAF) reaction of iminium salts and its application in a short and simple synthesis of the isoindolo[1, 2-a]isoquinoline core of the jamtine and hirsutine alkaloids. Tetrahedron Letters. 2010; 51 (52): 6822-6824. DOI: 10.1016/j.tetlet.2010.10.046.
52.    Zelisko N, Atamanyuk D, Ostapiuk Y, Bryhas A, Matiychuk V, Gzella A, Lesyk R. Synthesis of fused thiopyrano[2,3-d][1,3]thiazoles via hetero-Diels-Alder reaction related tandem and domino processes. Tetrahedron. 2015; 71 (50): 9501-9508. DOI: 10.1016/j.tet.2015.10.019.
53.    Pokhodylo NT, Matiychuk VS, Obushak MD. Synthesis of ethyl 4,5-disubstituted 2-azido-3-thiophenecarboxylates and use in the synthesis of thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidin-5(4H)-ones Tetrahedron. 2009; 65 (13): 2678-2683. DOI: 10.1016/j.tet.2009.01.086.
54.    Tymoshuk O, Oleksiv L, Khvalbota L, Chaban T, Patsay I. Spectrophotometric determination of ru(iv) using 5-hydroxyimino-4-imino-1,3-thiazolidin-2-one as a novel analytical reagent. Acta Chimica Slovenica 2019; 66 (1): 62–69, DOI:10.17344/acsi.2018.4448.
55.    Obushak ND, Lesyuk AI, Gorak YI, Matiichuk VS Mechanism of Meerwein arylation of furan derivatives. Russian Journal of Organic Chemistry. 2009; 45 (9): 1375-1381. DOI: 10.1134/S1070428009090103.
56.    Open-access antimicrobial screening program (
57.    Monks A, Scudiero D, Skehan P, Shoemaker R, Paull K, Vistica D, Hose C, Langley J, Cronise P, Vaigro-Wolff Monks A. Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. Journal Nature Cancer. 1991; 83: 757–766. DOI: 10.1093/jnci/83.11.757.
58.    Boyd MR, Paull KD. Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Development. 1995; 34: 91–109. DOI: 10.1002/ddr.430340203.
59.    Boyd MR, Teicher BA. In Cancer Drug Discovery and Development. Humana Press. 1997; 2: 23–43. DOI: 10.7124/bc.000971.
60.    Shoemaker RH. The NCI60 human tumour cell line anticancer drug screen. Nature Review Cancer. 2006; 6: 813–823. DOI: 10.1038/nrc1951.

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