Sunaina Aggarwal, Anju Goyal, Rajwinder Kaur
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Sunaina Aggarwal1, Anju Goyal*, Rajwinder Kaur2
1R.K.S.D. College of Pharmacy, Kaithal, Haryana-136027.
2Chitkara College of Pharmacy, Chitkara University, Punjab India.
Volume - 13,
Issue - 10,
Year - 2020
Five membered heterocyclic ring structures, oxadiazoles contain one oxygen and two nitrogen atoms. The synthesis of 1,2,4-oxadiazole involves conversion of cyanide to hydroxyl amine followed by 1,3-dipolar cycloaddition reaction to form a ringed structure. Ring also acts as bioisostere for carboxylic acid and carboxamide group. Further 1,2,4-oxadiazole derivatives have been evaluated for a wide range of medicinal applications.
Cite this article:
Sunaina Aggarwal, Anju Goyal, Rajwinder Kaur. Synthetic Procedures and Pharmacological Activities of 1,2,4-Oxadiazoles-A Review. Research J. Pharm. and Tech. 2020; 13(10):5026-5033. doi: 10.5958/0974-360X.2020.00880.X
1. Pace A, Buscemi S, Piccionello AP, Pibiri I. Recent advances in the chemistry of 1,2,4-oxadiazoles. Advances in Heterocyclic chemistry. 2015; 116: 85-136.
2. Kayukova LA. Synthsis of 1,2,4-oxadiazoles (A review). Pharmaceutical Chemistry Journal. 2005; 39: 32-40.
3. Bostrom J, Hogner A, Llinas A, Wellner E, Plowright AT. Oxadiazoles in medicinal chemistry. Journal of Medicinal Chemistry. 2012; 55: 1817-1830.
4. Bora RO, Dar B, Pradhan V, Farooqui M. [1,2,4]-oxadiazoles: synthesis and biological applications. Mini-Reviews in Medicinal Chemistry. 2014;14: 355-369.
5. Carbone M, Li Y, Irace C, Mollo E, Castelluccio F, Pascale AD Muscarine, imidaozle, oxazole and thiazole alkaloids. Organic Letters. 2011; 13(10): 2516-2519.
6. Polothi R, Raolji GSB, Kuchibhotla VS, Sheelam K, Tuniki B, Thodupunuri P. Synthesis and biological evaluation of 1,2,4-oxadiazole linked 1,3,4-oxadiazole derivatives as tubulin binding agents. Synthetic Communications. 2019; 49: 1-10.
7. Karad SC, Purohit VB, Thummar RP, Vaghasiya BK, Kamani RD, Thakor P, Thakkar VR, Thakkar SS, Ray A, Raval DK. Synthesis and biological screening of novel 2-morpholinoquinolone nucleus clubbed with 1,2,4-oxadiazole motifs. European Journal of Medicinal Chemistry. 2017; 126: 894-909.
8. Cao Y, Min C, Acharya S, Kim KM, Cheon SH. Design, synthesis and evaluation of bitopic arylpiperazinephenyl-1,2,4-oxadiazoles as preferential D3 receptor ligands. Bioorganic and Medicinal Chemistry. 2016; 24: 191-200.
9. Mohammadi-Khanaposhtani M, Shabani M, Faizi M, Aghaei I, Jahani R, Sharafi Z, Zafarghnandi NS, Mahdavi M, Akbarzedeh T, Emami S, Shafiee A, Foroumadi A. Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1,2,4-oxadiazoles as potential anticonvulsant agents. European Journal of Medicinal Chemistry. 2016; 112: 91-98.
10. Yoshimura A, Nguyen KC, Klasen SC, Postnikov PS, Yusubov MS, Saito A, Nemykin VN, Zhdankin V V. Hypervalent iodine-catalysed synthesis of 1,2,4-oxadiazoles from aldoximes and nitriles. Asian Journal of Organic Chemistry. 2016; 5: 1128-1133.
11. Outirite M, Lagrenee M, Hammouti B, Bentiss F. A rapid and an efficient synthesis for 3,5-disubstituted 1,2,4-oxadiazoles under microwave irradiation. Research on Chemical Intermediates. 2015; 41: 1601-1606.
12. Fortuna CG, Bonaccorso C, Bulbarelli A, Caltabiano G, Rizzi L, Goracci L, Musumarra G, Pace A, Piccionello AP, Guarcello A, Pierro P, Cocuzza CEA, Musumeci R. New Linezolid-like 1,2,4-oxadiazoles active against gram-positive multiresistant pathogens. European Journal of Medicinal Chemistry. 2013; 65: 533-545.
13. Neda I, Maftei CV, Fodor E, Jones PG, Franz MH, Kelter G, Fiebig H. Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties. Beilstein Journal of Organic Chemistry. 2013; 9: 2202-2215.
14. Shen J, Xia G, You X, Liu L, Liu H, Wang J, Shi Y, Li P, Xiong B, Liu X, Shen J. Design, synthesis and SAR of piperidyl-oxadiazoles as 11β-hydroxysteroid Dehydrogenase 1 inhibitors. European Journal of Medicinal Chemistry. 2013; 62: 1-10.
15. Ubaradka SR, Isloor AM, Shetty P, Isloor NA. Synthesis, characterization and their anticonvulsant, anti-inflammatory studies of some novel chromeno oxadiazoles. Medicinal Chemistry Research. 2013; 22: 1497-1503.
16. Jadhav RD, Kadam KS, Kandre S, Guha T, Reddy MMK, Brahma MK, Deshmukh NJ, Dixit A, Doshi L, Potdar N, Enose AA, Vishwakarma RA, Shivaramakrishnan H, Srinivasan S, Nemmani KVS, Gupte A, Gangopadhyay AK, Sharma R. Synthesis and biological evaluation of isoxazole, oxazole and oxadiazole containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors. European Journal of Medicinal Chemistry. 2012; 54: 324-342.
17. Kumar RS, Arumugam N, Sriram D, Almansour AIA. Solvent free, four-component synthesis and 1,3-dipolar cycloaddition of 4(H)-pyrans with nitrile oxides: Synthesis and discovery of antimycobacterial activity of enantiometrically pure 1,2,4-oxadiazoles. Eur. Journal of Medicinal Chemistry. 2012; 53: 416-423.
18. Bretanha LC, Teixeira VE, Ritter M, Siqueira GM, Cunico W, Pereira CM, Freitag R A. Ultrasound-promoted synthesis of 3-Trichloromethyl-5-alkyl(aryl)-1,2,4-oxadiazoles. Ultrasonics Sonochemistry. 2011; 18: 704-707.
19. Srivastava RM, Anjos JVD, Sinou D, Melo SJD, Filho RAWN, Nascimento SCD. Synthesis and cytotoxic profile of glycosyl-triazole linked to 1,2,4-oxadiazole moiety at C-5 through a straight-chain carbon and oxygen atoms. European Journal of Medicinal Chemistry. 2009; 44: 3571-3576.
20. Boger DL, Garfunkle J, Ezzili C, Rayl TJ, Hochstatter DG, Hwang IJ. Optimization of the central heterocycles of α-Ketoheterocycle inhibitors of fatty acid amide hydrolase. Journal of Medicinal Chemistry. 2008; 51: 4392-4403.
21. Huhtiniemi T, Suuronen T, Rinne VM, Wittekindt C, Kakkonen ML, Jarho E, Wallen EAA, Salminen A, Poso A, Leppanen J. Oxadiazole-carbonylaminothioureas as SIRT1 and SIRT2 inhibitors. Journal of Medicianl Chemistry. 2008; 51: 4377-4380.
22. Ivachtchenko AV, Koryakova AG, Ivanenkov YA, Ryzhova EA, Bulanova EA, Karapetian RN, Mikitas OV, Katrukha EA, Kazey VI, Okun I, Kravchenko DV, Lavrosky YV, Korzinov OM. Novel aryl and heteroaryl substituted N-[3-(4-phenylpiperazin-1-yl)propyl]-1,2,4-oxadiazole-5-carboxamides as selective GSK-3 inhibitors. Bioorganic and Medicinal Chemistry Letters. 2008; 18: 3661-3666.
23. Ono M, Haratake M, Saji H, Nakayama M. Development of novel β-amyloid probes based on 3,5-diphenyl-1,2,4-oxadiazole. Bioorganic and Medicinal Chemistry. 2008; 16: 6867-6872.
24. Tiwari SB, Kohli DV. Synthesis of 3-(5-bromo-2,3-dimethoxy-phenyl)-[1,2,4]oxadiazole analogues and their evaluation as anti-Parkinson’s agents. Medicinal Chemistry Research. 2008; 17: 386-398.
25. Cushman M, Sakamoto T, Cullen MD, Hartman TL, Watson KM, Buckheit RW, Pannecouque C, Clercq ED. Synthesis and anti-HIV activity of new metabolically stable alkenyldiarylmethane Non-Nucleoside reverse transcriptase inhibitors incorporating N-Methoxy imidoyl halide and 1,2,4-oxadiazole systems. Journal of Medicinal Chemistry. 2007; 50: 3314-3321.
26. Lankau HJ, Unverferth K, Grunwald C, Hartenhauer H, Heinecke K, Bernoster K, Dost R, Egerland U, Rundfeldt C. New GABA-modulating 1,2,4-oxadiazole derivatives and their anti-convulsant activity. European Journal of Medicinal Chemistry. 2007; 42: 873-879.
27. Boys ML, Schretzman LA, Chandrakumar NS, Tollefson MB, Mohler SB, Downs VL, Penning TD, Russel MA, Wendt JA, Chen BB, Stenmark HG, Wu H, Spangler DP, Clare M, Desai BN, Khanna IK, Nguyen MN, Duffin TP, Engleman VW, Finn MB, Freeman SK, Hanneke ML, Keene JL, Klover JA, Nickols GA, Nickols MA, Steininger CN, Westlin M, Westlin W, Yu YX, Wang Y, Dalton CR, Norring SA. Convergent, parallel synthesis of a series of β-substituted 1,2,4-oxadiazole butanoic acids as potent and selective. Bioorganic and Medicinal Chemistry Letters. 2006; 16: 839-844.
28. Palmer JT, Rydzewski RM, Mendonca RV, Sperandio D, Spencer JR, Hirschbein BL, Lohman J, Beltman J, Nguyen M, Liu L. Design and synthesis of selective keto-1,2,4-oxadiazole based tryptase inhibitors. Bioorganic and Medicinal Chemistry Letters. 2006; 16: 3434-3439.
29. Cai SX, Zhang HZ, Kasibhatla S, Kuemmerle J, Kemnitzer W, Manson KO, Qiu L, Crogan-Grundy C, Tseng B, Drewe J. Discovery and structure-activity relationship of 3-Aryl-5-Aryl-1,2,4-oxadiazoles as a new series of apoptosis inducers and potential anticancer agents. Journal of Medicinal Chemistry. 2005; 48: 5215-5223.
30. Wells MAW, Henninger TC, Spano SAF, Boggs CM, Matheis M, Ritchie DM, Argentieri DC, Wachter MP, Hlasta DJ. Synthesis and structure-activity relationships of 3,5-diarylisoxazoles and 3,5-diaryl-1,2,4-oxadiazoles, novel classes of small molecule interleukin-8 (IL-8) receptor antagonists. Bioorganic and Medicinal Chemistry Letters. 2006; 14: 4307-4311.
31. Werbovetz KA, Cottrell DM, Capers J, Salem MM, Fradley KD, Croft SL. Antikinetoplastid activity of 3-aryl-5-thiocyanatomethyl-1,2,4-oxadiazoles. Bioorganic and Medicinal Chemistry. 2004; 12: 2815-2824.
32. Hernandez JF, Hamze A, Fulcrand P, Martinez J. Synthesis of various 3-substituted 1,2,4-oxadiazole containing chiral β3- and α- amino acids from Fmoc-protected aspartic acid. Journal of Organic Chemistry. 2003; 68: 7316-7321.
33. Wang YG, Lin XF, Zhang J. Parallel synthesis of 4,5-dihydro-1,2,4-oxadiazoles using soluble polymer support. Tetrahedron Letters. 2003; 44: 4113-4115.
34. Gangloff AR, Litvak J, Shelton EJ, Sperandio D, Wang VR, Rice KD. Synthesis of 3,5-disubstituted-1,2,4-oxadiazoles using tetrabutylammonium fluoride as a mild and effective catalyst. Tetrahedron Letters. 2001; 42: 1441-1443.
35. Ainsworth C, Buting WE, Davenport J, Callender ME, McCowen MC. Anthelmintic activity of 1,2,4-oxadiazoles. Journal of Medicinal Chemistry. 1967; 10: 208-211.
36. Borg S, Estenne-Bouhtou G, Luthman K, Csoregh I, Hacksell U, Hesselink W. Synthesis of 1,2,4-oxadiazole, 1,3,4-oxadiazole and 1,2,4-triazole derived dipeptidomimetics. Journal of Organic Chemistry. 1995; 60: 3112-3120.
37. Clitherow JW, Beswick P, Irving WJ, Scopes DIC, Barnes JC, Clapham J, Brown JD, Evans DJ, Hayes AG. Novel 1,2,4-oxadiazoles as potent and selective histamine H3 receptor antagonists. Bioorganic and Medicinal Chemistry Letters. 1996; 6: 833-838.
38. Street LJ, Baker R, Book T, Kneen CO, Macleod AM, Merchant KJ, Showell GA, Saunders J, Herbert RH, Freedman SB, Harley EA. Synthesis and biological activity of 1,2,4-oxadiazole derivatives: highly potent and efficacious agonists for cortical muscarinic receptors. Journal of Medicinal Chemistry. 1990; 33: 2690-2697.
39. Sauerberg P, Kindtler JW, Nielsen L, Sheardown MJ, Honore T. Muscarinic cholinergic agonists and antagonists of 3-(3-Alkyl-1,2,4-oxadiazol-5-yl)-1,2,5,6-tetrahydropyridine type synthesis and structure-activity relationships. Journal of Medicinal Chemistry. 1991; 34: 687-692.
40. Li Z, Chen W, Hale JJ, Lynch CL, Mills SG, Hajdu R, Koehane CA, Rosenbach MJ, Milligan JA, Shie GJ, Chrebet G, Parent SA, Bergstrom J, Card D, Forrest M, Quackenbush EJ, Wickham LA, Vargas H, Evans RM, Rosen H, Mandala S. Discovery of potent 3,5-Diphenyl-1,2,4-oxadiazole Sphingosine-1-phosphate-1 (S1P1)receptor agonists with exceptional selectivity against S1P2 and S1P3. Journal of Medicinal Chemistry. 2005; 48: 6169-6173.