Abstract
The five-membered heterocyclic moieties comprising three hetero atoms or two hetero atoms (generally āNā and āSā) have gained significant interest among researchers as these compounds displayed significant therapeutic potential. These heterocycles can serve as a building block for the development of novel molecular structures. The chapter comprises the different synthetic strategies which provide diversified molecular libraries containing thiadiazoles, oxadiazoles, isoxazole, and isothiazole moieties. The therapeutic potential of some of the synthesized derivatives is also described in this chapter.
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References
Abdel-Wahab BF et al (2009) Synthesis and antimicrobial evaluation of some 1, 3-thiazole, 1, 3, 4-thiadiazole, 1, 2, 4-triazole, and 1, 2, 4-triazolo [3, 4-b][1, 3, 4]-thiadiazine derivatives including a 5-(benzofuran-2-yl)-1-phenylpyrazole moiety. Monatshefte FĆ¼r Chemie Chem Monthly 140(6):601ā605
Abdo NYM, Kamel MM (2015) Synthesis and anticancer evaluation of 1, 3, 4-oxadiazoles, 1, 3, 4-thiadiazoles, 1, 2, 4-triazoles and Mannich bases. Chem Pharm Bull 63(5):369ā376
Adams A, Slack R (1956) Isothiazole-a new mononuclear heterocyclic system, soc chemical industry 14 belgrave square, London sw1x 8ps, england, pp 1232ā1232
Adib M et al (2018) Reaction between chalcones, 1, 3-dicarbonyl compounds, and elemental sulfur: a one-pot three-component synthesis of substituted thiophenes. Synlett 29(12):1583ā1588
Ajay Kumar K, Lokanatha Rai K (2004) Synthesis and evaluation of antimicrobial activity of 4, 5-dihydro-1, 2, 4-oxadiazoles. Bul Chem Commun 36(4):249ā252
Alipour E et al (2011) Synthesis and antileishmanial activity of 5-(5-nitroaryl)-2-substituted-thio-1, 3, 4-thiadiazoles. J Enzyme Inhib Med Chem 26(1):123ā128
Allegretti PA, Ferreira EM (2013) Platinum-catalyzed cyclizations via carbene intermediates: syntheses of complementary positional isomers of isoxazoles. Chem Sci 4(3):1053ā1058
Almasirad A et al (2004) Synthesis and anticonvulsant activity of new 2-substituted-5-[2-(2-fluorophenoxy) phenyl]-1, 3, 4-oxadiazoles and 1, 2, 4-triazoles. Bioorg Med Chem Lett 14(24):6057ā6059
Alvarez-Builla J et al (2011) Modern heterocyclic chemistry, 4, vol Set. Wiley
Amarasinghe KK et al (2006) One-pot synthesis of 1, 2, 4-oxadiazoles from carboxylic acid esters and amidoximes using potassium carbonate. Tetrahedron Lett 47(22):3629ā3631
Amir M et al (2007) Non-carboxylic analogues of naproxen: design, synthesis, and pharmacological evaluation of some 1, 3, 4-oxadiazole/thiadiazole and 1, 2, 4-triazole derivatives. Archiv Der Pharmazie Int J Pharm Med Chem 340(11):577ā585
Anand D et al (2015) Substrate controlled synthesis of benzisoxazole and benzisothiazole derivatives via PhI (OAc) 2-mediated oxidation followed by intramolecular oxidative O-N/SāN bond formation. J Org Chem 80(24):12410ā12419
Anderson GW et al (1942) Studies in chemotherapy. VI. Sulfanilamido heterocycles1. J Am Chem Soc 64(12):2902ā2905
Attanasi OA et al (2005) Solvent-free reaction of some 1, 2-diaza-1, 3-butadienes with phosphites: Environmentally friendly access to new diazaphospholes and E-hydrazonophosphonates. J Org Chem 70(10):4033ā4037
Augustine JK et al (2009) PTSAā ZnCl2: An efficient catalyst for the synthesis of 1, 2, 4-oxadiazoles from amidoximes and organic nitriles. J Org Chem 74(15):5640ā5643
Balasankar T et al (2005) Synthesis and antibacterial activity of some 5-(4-biphenylyl)-7-aryl [3, 4-d][1, 2, 3]-benzothiadiazoles. Eur J Med Chem 40(7):728ā731
Barday M et al (2017) Cross-coupling of Ī±-carbonyl sulfoxonium ylides with CāH bonds. Angew Chem 129(42):13297ā13301
Baron H et al (1904) CLXXV.āthe formation and reactions of imino-compounds. Part I. condensation of ethyl cyanoacetate with its sodium derivative. J Chem Soc Trans 85:1726ā1761
Barton P (2018) The synthesis of 3-amino-5-arylisothiazoles from propynenitriles. Tetrahedron Lett 59(9):815ā817
Bezbaruah P et al (2012) Microwave-assisted novel and efficient one-pot synthesis of fused steroidal and non-steroidal isothiazoles. Tetrahedron Lett 53(33):4389ā4392
Bostrƶm J et al (2012) Oxadiazoles in medicinal chemistry. J Med Chem 55(5):1817ā1830
Boyd G et al (2014) Science of synthesis: houben-weyl methods of molecular transformations Vol. 11: five-membered hetarenes with one chalcogen and one additional heteroatom, Georg Thieme Verlag.
Bretanha LC et al (2009) Preparation of trichloroacetoamidoxime in aqueous media and application in one pot synthesis of 1, 2, 4-oxadiazoles. ARKIVOC 12:1
Cai B-G et al (2019) [3+ 2]-Cycloaddition of 2 H-azirines with nitrosoarenes: visible-light-promoted synthesis of 2, 5-dihydro-1, 2, 4-oxadiazoles. Org Lett 21(11):4234ā4238
Cao X et al (2016) Synthesis and biological evaluation of novel Ļ1 receptor ligands for treating neuropathic pain: 6-hydroxypyridazinones. J Med Chem 59(7):2942ā2961
Cao X et al (2019) Synthesis and biological evaluation of sigmaā1 (Ļ1) receptor ligands based on phenylā1, 2, 4āoxadiazole derivatives. Chem Biodivers 16(3):e1800599
Carbone M et al (2011) Structure and cytotoxicity of phidianidines A and B: first finding of 1, 2, 4-oxadiazole system in a marine natural product. Org Lett 13(10):2516ā2519
Cardona P-J (2012) Understanding tuberculosis: new approaches to fighting against drug resistance, BoDābooks on demand
Caron M (1986) Convenient preparation of 5-alkyl-4-carbalkoxy-1, 2, 3-thiadiazoles. J Org Chem 51(21):4075ā4077
Catanese B, Silvestrini B (1964) Research on the metabolism of 5-beta-diethylamino-3-alpha-phenylpropyl-1, 2, 4-oxadiazole. Boll Chim Farm 103:447
Chai L et al (2018) One-pot synthesis of 3-aryl-5-amino-1, 2, 4-thiadiazoles from imidates and thioureas by i2-mediated oxidative construction of the N-S bond. Eur J Org Chem 2018(31):4338ā4344
Chai L et al (2017) One-pot synthesis of 3, 5-disubstituted 1, 2, 4-thiadiazoles from nitriles and thioamides via I 2-mediated oxidative formation of an N-S bond. Org Biomol Chem 15(39):8410ā8417
Chen J et al (2016a) TBAI-catalyzed reaction between N-Tosylhydrazones and sulfur: a procedure toward 1, 2, 3-thiadiazole. J Org Chem 81(1):271ā275
Chen L et al (2017) Synthesis of 1, 2, 3-thiadiazole and thiazole-based strobilurins as potent fungicide candidates. J Agric Food Chem 65(4):745ā751
Chen Y, Willis MC (2015) An aryne-based route to substituted benzoisothiazoles. Org Lett 17(19):4786ā4789
Chen Z et al (2016b) Benzo [d][1, 2, 3] thiadiazole (isobt): synthesis, structural analysis, and implementation in semiconducting polymers. Chem Mater 28(17):6390ā6400
Chidananda N et al (2012) Facile synthesis, characterization and pharmacological activities of 3, 6-disubstituted 1, 2, 4-triazolo [3, 4-b][1, 3, 4] thiadiazoles and 5, 6-dihydro-3, 6-disubstituted-1, 2, 4-triazolo [3, 4-b][1, 3, 4] thiadiazoles. Eur J Med Chem 51:124ā136
Christoforou IC et al (2006) 1, 2, 3-Dithiazole chemistry in heterocyclic synthesis. ARKIVOC 7:207ā223
Cikotiene I et al (2009) 5-Aryl-4-(5-substituted-2, 4-dihydroxyphenyl)-1, 2, 3-thiadiazoles as inhibitors of Hsp90 chaperone. Bioorg Med Chem Lett 19(4):1089ā1092
Clerici F et al (2001) Synthesis of 2-amino-5-sulfanyl-1, 3, 4-thiadiazole derivatives and evaluation of their antidepressant and anxiolytic activity. J Med Chem 44(6):931ā936
Coupar I et al (1969) Effect of aminophylline, butalamine and imolamine on human isolated smooth muscle. J Pharm Pharmacol 21(7):474ā475
Cunha FS et al (2018) Synthesis and antibacterial evaluation of 3, 5-Diaryl-1, 2, 4-oxadiazole derivatives. J Braz Chem Soc 29(11):2405ā2416
Da Settimo F et al (2005) Naphtho [1, 2-d] isothiazole acetic acid derivatives as a novel class of selective aldose reductase inhibitors. J Med Chem 48(22):6897ā6907
Dabiri M et al (2007) Silica sulfuric acid: an efficient and versatile acidic catalyst for the rapid and ecofriendly synthesis of 1, 3, 4-oxadiazoles at ambient temperature. Synth Commun 37(7):1201ā1209
Dai H et al (2016) Synthesis and bioactivities of novel pyrazole oxime derivatives containing a 1, 2, 3-thiadiazole moiety. Bioorg Med Chem Lett 26(18):4504ā4507
Davison EK, Sperry J (2016) Synthesis of the 1, 2, 4-thiadiazole alkaloids polycarpathiamines A and B. Organic Chem Front 3(1):38ā42
Dighe NSS, RB, Jain DA (2013) Design, synthesis, antimicrobial and antiinflammatory activities of some N-{3-[2-(Substituted Sulfanyl)ā1h-enzimidazol-1-Yl]-4h (Substituted)-1, 2, 4ātriazole and 2-(substituted sulfanyl)-1-[5-substituted-1, 3, 4āoxadiazol-2-Yl]-1h-benzimidazole derivatives. Int J Pharma Bio 4(4):484ā496
Dogan HN et al (2002) Synthesis of new 2, 5-disubstituted-1, 3, 4-thiadiazoles and preliminary evaluation of anticonvulsant and antimicrobial activities. Bioorg Med Chem 10(9):2893ā2898
Dravyakar B et al (2008) Design and syntheses of some new diphenylaminoisoxazolines as potent anti-inflammatory agent
Duan P et al (2014) Palladium-catalyzed benzo [d] isoxazole Synthesis by CāH Activation/[4+ 1] Annulation Chem, Sci
Dwivedi V et al (2017) A stereoselective thiocyanate conjugate addition to electron deficient alkynes and concomitant cyclization to N, S-heterocycles. Chem Commun 53(80):11060ā11063
Erlanson DA et al (2016) Twenty years on: the impact of fragments on drug discovery. Nat Rev Drug Discovery 15(9):605
Farghaly TA et al (2015) New and efficient approach for synthesis of novel bioactive [1, 3, 4] thiadiazoles incorporated with 1, 3-thiazole moiety. Eur J Med Chem 97:320ā333
Farshori NN et al (2017) A facile one-pot synthesis of novel 2, 5-disubstituted-1, 3, 4-oxadiazoles under conventional and microwave conditions and evaluation of their in vitro antimicrobial activities. Arab J Chem 10:S2853āS2861
Filimonov VO et al (2017) Switchable synthesis of 4, 5-functionalized 1, 2, 3-thiadiazoles and 1, 2, 3-triazoles from 2-cyanothioacetamides under diazo group transfer conditions. J Org Chem 82(8):4056ā4071
Foroumadi A et al (2005) Synthesis and in vitro leishmanicidal activity of 2-(5-nitro-2-furyl) and 2-(5-nitro-2-thienyl)-5-substituted-1, 3, 4-thiadiazoles. Bioorg Med Chem Lett 15(8):1983ā1985
Foroumadi A et al (2004) Antituberculosis agents x. synthesis and evaluation ofIn Vitro antituberculosis activity of 2-(5-nitro-2-furyl)-and 2-(1-methyl-5-nitro-1H-imidazol-2-yl)-1, 3, 4-thiadiazole derivatives. Arch Pharmacal Res 27(5):502ā506
Frija LM et al (2017) Building 1, 2, 4-thiadiazole: ten years of progress. Eur J Org Chem 2017(19):2670ā2682
Gritsan N, Zibarev A (2011) Chalcogen-nitrogen Ļ-heterocyclic radical anion salts: the synthesis and properties. Russ Chem Bull 60(11):2131ā2140
GrĆ¼nanger P, Vita-Finzi P (2009) Isoxazoles, part 1. Wiley
GrĆ¼nanger P et al (2009) Isoxazoles, part 2. Wiley
Hackler RE et al (1989) The syntheses of 5-amino-3-t-butylisothiazole and 3-amino-5-t-butylisothiazole. J Heterocycl Chem 26(6):1575ā1578
Haider S et al (2015) 1, 3, 4-thiadiazoles: a potent multi targeted pharmacological scaffold. Eur J Med Chem 92:156ā177
Hamad NS et al (2010) Amino acid derivatives, part 4: synthesis and anti-hiv activity of new naphthalene derivatives. Arch Pharm 343(7):397ā403
Hamama W et al (2017) Synthesis and biological evaluation of some novel isoxazole derivatives. J Heterocycl Chem 54(1):341ā346
Harigae R et al (2014) Preparation of 3, 5-disubstituted pyrazoles and isoxazoles from terminal alkynes, aldehydes, hydrazines, and hydroxylamine. J Org Chem 79(5):2049ā2058
Hasui T et al (2011) Identification of benzoxazin-3-one derivatives as novel, potent, and selective nonsteroidal mineralocorticoid receptor antagonists. J Med Chem 54(24):8616ā8631
Hayat F et al (2010) Synthesis, characterization, antiamoebic activity and cytotoxicity of novel 2-(quinolin-8-yloxy) acetohydrazones and their cyclized products (1, 2, 3-thiadiazole and 1, 2, 3-selenadiazole derivatives). Eur J Med Chem 45(12):6127ā6134
Hermit MB et al (2004) Mutation-induced quisqualic acid and ibotenic acid affinity at the metabotropic glutamate receptor subtype 4 ligand selectivity results from a synergy of several amino acid residues. J Biol Chem 279(33):34811ā34817
Hokfelt B, Jonsson A (1962) Hypoglycemic activity in relation to chemical structure of potential oral antidiabetic substances. III. 2-benzenesulfonamido-5-alkyl-1, 3, 4-thiadiazoles and-oxadiazoles. J Med Chem 5(2):247ā257
Holla BS et al (2005) Synthesis and anticancer activity studies on some 2-chloro-1, 4-bis-(5-substituted-1, 3, 4-oxadiazol-2-ylmethyleneoxy) phenylene derivatives
Howard HR et al (1996) 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem 39(1):143ā148
Hu Y et al (1999) Parallel synthesis of 1, 2, 3-thiadiazoles employing a ācatch and releaseā strategy. J Org Chem 64(3):1049ā1051
Hu Y et al (2014) 1, 3, 4-thiadiazole: synthesis, reactions, and applications in medicinal, agricultural, and materials chemistry. Chem Rev 114(10):5572ā5610
Huang H et al, Mild CāC bond formation via lewis acid catalyzed oxetane ring opening with soft carbon nucleophiles. Angewandte Chemie
Hui X-P et al (2002) Synthesis and antibacterial activities of 1, 3, 4-oxadiazole derivatives containing 5-methylisoxazole moiety
Hurd CD, Mori RI (1955) On acylhydrazones and 1, 2, 3-thiadiazoles. J Am Chem Soc 77(20):5359ā5364
Ikegami F et al (2000) Synthesis and pharmacological activity of O-(5-isoxazolyl)-L-serine. Chem Pharm Bull 48(2):278ā280
In SJSW (2008) Comprehensive heterocyclic chemistry III Vol 5: Katritzky AR. Ramsden CA. Scriven EFV. Taylor RJK, Elsevier Science Oxford
Ishikawa T et al (2017) Coupled flavin-iodine redox organocatalysts: Aerobic oxidative transformation from N-tosylhydrazones to 1, 2, 3-thiadiazoles. ACS Catal 7(8):4986ā4989
Jain AK et al (2013) 1, 3, 4-Thiadiazole and its derivatives: a review on recent progress in biological activities. Chem Biol Drug Des 81(5):557ā576
Jatav V et al (2008) CNS depressant and anticonvulsant activities of some novel 3-[5-substituted 1, 3, 4-thiadiazole-2-yl]-2-styryl quinazoline-4 (3H)-ones. Eur J Med Chem 43(9):1945ā1954
Jeong Y et al (2014) Direct synthesis of 4-fluoroisoxazoles through gold-catalyzed cascade cyclizationāfluorination of 2-alkynone O-methyl oximes. J Org Chem 79(14):6444ā6455
Jiang J et al (2018) Aniline ortho CāH sulfuration/cyclization with elemental sulfur for efficient synthesis of 2-substituted benzothiazoles under metal-free conditions. Adv Synth Catal 360(8):1622ā1627
Joseph L, George M (2016) Evaluation of in vivo and in vitro anti-inflammatory activity of novel isoxazole series. Euro Int J Sci Technol 5(3):35ā42
Jubie S et al (2015) Design, synthesis and antidepressant activities of some novel fatty acid analogues. Med Chem Res 24(4):1605ā1616
Kagthara PR et al (1999) Synthesis of 2, 5-disubstituted 1, 3, 4-oxadiazoles as biologically active heterocycles
Kalirajan R et al (2012) Docking studies, synthesis, characterization and evaluation of their antioxidant and cytotoxic activities of some novel isoxazole-substituted 9-anilinoacridine derivatives. Sci World J 2012
Kalogirou AS et al (2016) The acid and/or thermal mediated ring contraction of 4 h-1, 2, 6-thiadiazines to afford 1, 2, 5-thiadiazoles. Org Lett 18(16):4056ā4059
Kankala S et al (2011) N-Heterocyclic carbene-catalyzed 1, 3-dipolar cycloaddition reactions: a facile synthesis of 3, 5-di-and 3, 4, 5-trisubstituted isoxazoles. Org Biomol Chem 9(22):7869ā7876
Kerimov I et al (2012) Design and one-pot and microwave-assisted synthesis of 2-amino/5-aryl-1, 3, 4-oxadiazoles bearing a benzimidazole moiety as antioxidants. Arch Pharm 345(7):549ā556
Khan M et al (2004) Synthesis and biological activity of some isoniazid based 1, 3, 4-oxadiazole derivatives
Khanage S et al (2012) Synthesis and pharmacological evaluation of isoxazole derivatives containing 1, 2, 4-triazole Moiety. Marmara Pharm J 16(2):134ā140
Khazi IAM et al (2011) Chemistry of imidazo [2, 1-b][1, 3, 4] thiadiazoles. Tetrahedron (Oxford. Print) 67(19)
Kim H-Y et al (2014) Copper-catalyzed synthesis of 3-substituted-5-amino-1, 2, 4-thiadiazoles via intramolecular N-S bond formation. Tetrahedron 70(45):8737ā8743
Kolavi G et al (2006) Synthesis and evaluation of antitubercular activity of imidazo [2, 1-b][1, 3, 4] thiadiazole derivatives. Bioorg Med Chem 14(9):3069ā3080
Konstantinova LS et al (2014) 1, 2, 5-Thiadiazole 2-oxides: selective synthesis, structural characterization, and electrochemical properties. Tetrahedron 70(35):5558ā5568
Konstantinova LS et al (2014) Recent developments in the synthesis and applications of 1, 2, 5-Thia-and selenadiazoles. a review. Org Prep Proced Int 46(6):475ā544
Konstantinova LS et al (2015) Direct exchange of oxygen and selenium atoms in the 1, 2, 5-oxadiazoles and 1, 2, 5-selenadiazoles by action of sulfur monochloride. Molecules 20(8):14522ā14532
Kozikowski AP et al (1998) Ī±-substituted quisqualic acid analogs: new metabotropic glutamate receptor group II selective antagonists. Bioorg Med Chem Lett 8(5):447ā452
Krehan D et al (2006) Potent 4-arylalkyl-substituted 3-isothiazolol GABAA competitive/noncompetitive antagonists: synthesis and pharmacology. J Med Chem 49(4):1388ā1396
Kumar A et al (2012) Ionic liquid as soluble support for synthesis of 1, 2, 3-thiadiazoles and 1, 2, 3-selenadiazoles. J Org Chem 77(20):9391ā9396
Kumar D et al (2010) Synthesis and anticancer activity of 5-(3-indolyl)-1, 3, 4-thiadiazoles. Eur J Med Chem 45(10):4664ā4668
Kumar H et al (2008) 1, 3, 4-Oxadiazole/thiadiazole and 1, 2, 4-triazole derivatives of biphenyl-4-yloxy acetic acid: synthesis and preliminary evaluation of biological properties. Eur J Med Chem 43(12):2688ā2698
Lamers P, Bolm C (2018) Tetrahydrobenzo [c] thieno [2, 1-e] isothiazole 4-oxides: three-dimensional heterocycles as cross-coupling building blocks. Org Lett 20(1):116ā118
Lamers P et al (2016) Benzo [c] isothiazole 2-oxides: three-dimensional heterocycles with cross-coupling and functionalization potential. Adv Synth Catal 358(22):3649ā3653
Lan Y et al (2014) Synthesis and biological evaluation of novel sigma-1 receptor antagonists based on pyrimidine scaffold as agents for treating neuropathic pain. J Med Chem 57(24):10404ā10423
Lee J et al (2010) Novel C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents: 1, 3, 4-thiadiazolylmethylphenyl glucoside congeners. Bioorg Med Chem 18(6):2178ā2194
Lipnicka U et al (2005) New amides of 5-acylamino-3-methyl-4-isothiazolecarboxylic acid and their immunotropic activity. Archiv Der Pharmazie Int J Pharm Med Chem 338(7):322ā328
Liu B-B et al (2018) Cascade trisulfur radical anion (S3ā¢ā) addition/electron detosylation process for the synthesis of 1, 2, 3-thiadiazoles and isothiazoles. J Org Chem 83(17):10281ā10288
Madhavi K et al (2010) Synthesis and evaluation of 3-methyl-4-nitro-5-(substitutedstyryl) isoxazoles for antioxidant and anti-inflammatory activities. RJPBCS 1:1073ā1082
Maftei CV et al (2013) Synthesis and characterization of novel bioactive 1, 2, 4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties. Beilstein J Org Chem 9(1):2202ā2215
Mahajan PS et al (2015) Ammonium persulfate activated DMSO as a one-carbon synthon for the synthesis of methylenebisamides and other applications. RSC Adv 5(123):101641ā101646
Maske PP et al (2012) Synthesis and antiprotozoal activity of nitro and halogeno substituted some novel mercaptobenzimidazole derivatives. Der Pharma Chemica 4(3):1283ā1287
Matsushita M et al (2005) Perospirone, a novel antipsychotic drug, inhibits marble-burying behavior via 5-HT1A receptor in mice: implications for obsessive-compulsive disorder. J Pharmacol Sci 99(2):154ā159
Matysiak J, Malinski Z (2007) 2-(2, 4-dihydroxyphenyl)-1, 3, 4-thiadiazole analogues: antifungal activity in vitro against Candida species. Russ J Bioorg Chem 33(6):594
Mayhoub AS et al (2011) An unexpected synthesis of 3, 5-diaryl-1, 2, 4-thiadiazoles from thiobenzamides and methyl bromocyanoacetate. Tetrahedron Lett 52(38):4941ā4943
Mayhoub AS et al (2012) Optimizing thiadiazole analogues of resveratrol versus three chemopreventive targets. Bioorg Med Chem 20(1):510ā520
Mazumder A, Shaharyar M (2015) Synthesis, antibacterial and anticancer evaluation of 5-substituted (1, 3, 4-oxadiazol-2-yl) quinoline. Med Chem Res 24(6):2514ā2528
McDonald CM et al (2017) Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390(10101):1489ā1498
McIntosh ML et al (2012) Highly regioselective nitrile oxide dipolar cycloadditions with ortho-nitrophenyl alkynes. Org Biomol Chem 10(46):9204ā9213
Mo SK et al (2019) Metal-and oxidant-free electrosynthesis of 1, 2, 3-thiadiazoles from element sulfur and N-tosyl hydrazones. Adv Synth Catal 361(8):1756ā1760
Mohammadi-Khanaposhtani M et al (2015) Potent acetylcholinesterase inhibitors: design, synthesis, biological evaluation, and docking study of acridone linked to 1, 2, 3-triazole derivatives. Eur J Med Chem 92:799ā806
Mohammadi-Khanaposhtani M et al (2016) Design, synthesis, pharmacological evaluation, and docking study of new acridone-based 1, 2, 4-oxadiazoles as potential anticonvulsant agents. Eur J Med Chem 112:91ā98
Moshafi MH et al (2011) 5-Nitroimidazole-based 1, 3, 4-thiadiazoles: heterocyclic analogs of metronidazole as anti-helicobacter pylori agents. Arch Pharm 344(3):178ā183
Murray CW, Rees DC (2009) The rise of fragment-based drug discovery. Nat Chem 1(3):187ā192
Nagaraj CK et al (2011) 1, 3, 4-oxadiazole: a potent drug candidate with various pharmacological activities. Int J Pharm Pharm Sci 3(3):9ā16
Navarro M et al (2003) Synthesis, characterization, DNA binding study and biological activity against Leishmania mexicana of [Cu (dppz) 2] BF4. J Inorg Biochem 97(4):364ā369
Niu P et al (2015) Synthesis of 2-amino-1, 3, 4-oxadiazoles and 2-amino-1, 3, 4-thiadiazoles via sequential condensation and I2-mediated oxidative C-O/CāS bond formation. J Org Chem 80(2):1018ā1024
Noei J, Khosropour AR (2013) A novel process for the synthesis of 3, 5-diaryl-1, 2, 4-thiadiazoles from aryl nitriles. Tetrahedron Lett 54(1):9ā11
Oakdale JS et al (2014) Ruthenium-catalyzed cycloaddition of 1-haloalkynes with nitrile oxides and organic azides; synthesis of 4-halo isoxazoles and 5-halo triazoles. Chem (weinheim an Der Bergstrasse, Germany) 20(35):11101
Ćnkol T et al (2008) Synthesis and antimicrobial activity of new 1, 2, 4-triazole and 1, 3, 4-thiadiazole derivatives. J Enzyme Inhib Med Chem 23(2):277ā284
OruƧ EE et al (2004) 1, 3, 4-thiadiazole derivatives. Synthesis, structure elucidation, and structureāantituberculosis activity relationship investigation. J Med Chem 47(27):6760ā6767
Panda S et al (2009) Synthesis, antiinflammatory and antibacterial activity of novel indolyl-isoxazoles. Indian J Pharm Sci 71(6):684
Patil R, Biradar J (1999) Synthesis and biological activities of new 3, 5-disubstituted-2-(ethyl-5ā²-thioxo-1ā², 3ā², 4ā²-oxadiazol-4ā²-ethylacetate-2ā²-yl) indoles,-2-(5ā²-thioxo-1ā², 3ā², 4ā²-oxadiazol-4ā²methylcarboxyhydrazide-2ā²-yl) indoles and-2-(5ā²-thioxo-1ā², 3ā², 4ā²-oxadiazol-4ā²alkyl-2ā²-yl) indoles
PKumar NB, Jayaka NG (2015) Anti-microbial activity of novel isoxazole containing quinazolinonederivatives. Asian J Res Chem Pharm Sci 3(1):2015
Poulain RF et al (2001) Parallel synthesis of 1, 2, 4-oxadiazoles from carboxylic acids using an improved, uronium-based, activation. Tetrahedron Lett 42(8):1495ā1498
Raap R, Micetich RG (1968) Penicillins and cephalosporins from isothiazolylacetic acids. J Med Chem 11(1):70ā73
Rajak H et al (2009) Synthesis of novel 2, 5-disubstituted 1, 3, 4-thiadiazoles for their potential anticonvulsant activity: pharmacophoric model studies. Archiv Der Pharmazie Int J Pharm Med Chem 342(8):453ā461
Rajak H et al (2013) Novel limonene and citral based 2, 5-disubstituted-1, 3, 4-oxadiazoles: a natural product coupled approach to semicarbazones for antiepileptic activity. Bioorg Med Chem Lett 23(3):864ā868
Regiec A et al (2006) New isothiazole derivatives: Synthesis, reactivity, physicochemical properties and pharmacological activity. Archiv Der Pharmazie Int J Pharm Med Chem 339(7):401ā413
Rezki N et al (2015) Synthesis of novel 2, 5-disubstituted-1, 3, 4-thiadiazoles clubbed 1, 2, 4-triazole, 1, 3, 4-thiadiazole, 1, 3, 4-oxadiazole and/or schiff base as potential antimicrobial and antiproliferative agents. Molecules 20(9):16048ā16067
RodrĆguez MR et al (2017) Catalytic nitrene transfer to alkynes: a novel and versatile route for the synthesis of sulfinamides and isothiazoles. Angew Chem Int Ed 56(42):12842ā12847
Rotbart HA et al (2001) Treatment of potentially life-threatening enterovirus infections with pleconaril. Clin Infect Dis 32(2):228ā235
Rovira AR et al (2017) Expanding a fluorescent RNA alphabet: synthesis, photophysics and utility of isothiazole-derived purine nucleoside surrogates. Chem Sci 8(4):2983ā2993
Sagar P et al (2017) Synthesis & evaluation of isoxazole for their antimicrobial activity. Int J Compr Adv Pharmacol 2(1):19ā26
Salgın-GƶkÅen U et al (2007) 1-Acylthiosemicarbazides, 1, 2, 4-triazole-5 (4H)-thiones, 1, 3, 4-thiadiazoles and hydrazones containing 5-methyl-2-benzoxazolinones: synthesis, analgesic-anti-inflammatory and antimicrobial activities. Bioorg Med Chem 15(17):5738ā5751
Sauer AC et al (2019) A straightforward and high-yielding synthesis of 1, 2, 4-oxadiazoles from chiral n-protected Ī±-amino acids and amidoximes in acetone-water: an eco-friendly approach. J Chem 2019
Seo B et al (2016) Synthesis of isothiazole via the rhodium-catalyzed transannulation of 1, 2, 3-thiadiazoles with nitriles. Org Lett 18(19):5050ā5053
Shah A-u-HA et al (2009) Iodoxolone-based hypervalent iodine reagents. Organic Lett 11(16):3578ā3581
Shah V et al (1996) Synthesis of 2-arylamino-5-substituted-1, 3, 4-oxadiazoles by the reaction of appropriately substituted thiosemicarbazides in presence of iodine in sodium hydroxide. Ind J Chem 35:111ā115
Shailaja M et al (2011) Synthesis of novel 3, 5-disubstituted-4, 5-dihydroisoxazoles and 3, 4, 5-trisubstituted isoxazoles and their biological activity
Sharma R et al (2014) Some substituted 1, 3, 4-thiadiazoles: a novel centrally acting agents. Med Chem Res 23(1):252ā258
Sharma S et al (2002) Synthesis of some newer indolyl-thiadiazolyl-pyrazolines and indolyl-oxadiazolyl-pyrazolines as potential anti-inflammatory agents
Sheehan JC, Izzo PT (1949) The reaction of diazomethane with isocyanates and isothiocyanates. J Am Chem Soc 71(12):4059ā4062
Shukla G et al (2016) Metal-and catalyst-free, formal [4+ 1] annulation via tandem C=O/C=S functionalization: one-pot access to 3, 5-disubstituted/annulated isothiazoles. Org Lett 18(10):2451ā2454
Singh A (2004) Synthesis and molluscicidal activity of (2-substituted)-spiro (cyclohexane)-1Ź¹, 5-[1, 3, 4] oxa/thiadiazolo [3, 2-c] thiazolines
Singh MS et al (2013) Eco-efficient, regioselective and rapid access to 4, 5-disubstituted 1, 2, 3-thiadiazoles via [3+ 2] cycloaddition of Ī±-enolicdithioesters with tosyl azide under solvent-free conditions. Green Chem 15(4):954ā962
Singh SJ et al (2016) Synthesis of 2-amino-substituted-1, 3, 4-thiadiazoles via 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ) mediated intramolecular C-S bond formation in thiosemicarbazones. Tetrahedron Lett 57(9):1044ā1047
Solankee A et al (2013) Antimicrobial evaluation of some novel isoxazoles, cyanopyridines and pyrimidinthiones
Stabile P et al (2010) Mild and convenient one-pot synthesis of 1, 3, 4-oxadiazoles. Tetrahedron Lett 51(37):4801ā4805
Stimson L et al (2005) Isothiazolones as inhibitors of PCAF and p300 histone acetyltransferase activity. Mol Cancer Ther 4(10):1521ā1532
Sun Y et al (2014) Copper (II)-mediated homocoupling of thioamides for the synthesis of 1, 2, 4-thiadiazoles. Eur J Org Chem 2014(20):4239ā4243
Swayze EE et al (1997) Synthesis, antiproliferative and antiviral activity of imidazo [4, 5-d] isothiazole nucleosides as 5: 5 fused analogs of nebularine and 6-methylpurine ribonucleoside. J Med Chem 40(5):771ā784
Tang S et al (2009) Efficient and regioselective one-pot synthesis of 3-substituted and 3, 5-disubstituted isoxazoles. Org Lett 11(17):3982ā3985
Tang S et al (2010) Efficient and regioselective synthesis of 5-hydroxy-2-isoxazolines: versatile synthons for isoxazoles, Ī²-lactams, and Ī³-amino alcohols. J Org Chem 75(6):1961ā1966
Todres ZV (2011) Chalcogenadiazoles: chemistry and applications. CRC Press
Tumula N et al (2017) I2-catalyzed oxidative N-S bond formation: metal-free regiospecific synthesis of N-fused and 3, 4-disubstituted 5-imino-1, 2, 4-thiadiazoles. J Org Chem 82(10):5310ā5316
Tumula N et al (2018) Hypervalent Iodine (III)-mediated solvent-free, regioselective synthesis of 3, 4-disubstituted 5-imino-1, 2, 4-thiadiazoles and 2-aminobenzo [d] thiazoles. Adv Synth Catal 360(15):2806ā2812
Upare AA et al (2019) Design, synthesis and biological evaluation of (E)-5-styryl-1, 2, 4-oxadiazoles as anti-tubercular agents. Bioorg Chem 86:507ā512
Vadivelu A et al (2015) In vitro antibacterial activity of few novel 2ā(heteroarylamino)ā5ā(aryl)ā1, 3, 4āthiadiazoles. ChemInform 46(22)
Van der Peet PL et al (2013) A click chemistry approach to 5, 5ā²-disubstituted-3, 3ā²-bisisoxazoles from dichloroglyoxime and alkynes: Luminescent organometallic iridium and rhenium bisisoxazole complexes. J Org Chem 78(14):7298ā7304
Vanajatha G, Reddy VP (2016) High yielding protocol for oxidative dimerization of primary thioamides: a strategy toward 3, 5-disubstituted 1, 2, 4-thiadiazoles. Tetrahedron Lett 57(22):2356ā2359
Verma S et al (2011) Synthesis and antimicrobial activity of thiazolidine derivatives of thiazole. Int J Pharm Res Dev 11:73ā81
Vinaya K et al (2019) One-pot synthesis of 3, 5-diaryl substituted-1, 2, 4-oxadiazoles using gem-dibromomethylarenes. Can J Chem 97(9):690ā696
Vitale RM et al (2013) Minimalist hybrid ligand/receptor-based pharmacophore model for CXCR4 applied to a small-library of marine natural products led to the identification of phidianidine a as a new CXCR4 ligand exhibiting antagonist activity. ACS Chem Biol 8(12):2762ā2770
Wageeh S, E1-Hamouly, E1-Khamry AMA, Abbas EMH (2006) Synthesis of new 4-aryl-isoxazolo [5, 4-d] pyrimidin-6-one (thione) and 4-aryl-pyrazolo [3, 4-d]-pyrimidin-6-one derivatives of potential antihypertensive activity. Indian J Chem B 45:2091ā2098
Wang B et al (2017a) Synthesis of 5-amino and 3, 5-diamino substituted 1, 2, 4-thiadiazoles by I2-mediated oxidative N-S bond formation. J Org Chem 82(11):5898ā5903
Wang H et al (2011) Synthesis and insecticidal activity of N-tert-butyl-N, Nā²-diacylhydrazines containing 1, 2, 3-thiadiazoles. J Agric Food Chem 59(2):628ā634
Wang H et al (2016) Halocyclizations of unsaturated sulfoximines. Org Lett 18(10):2431ā2434
Wang L et al (2012) Synthesis of 3, 5-disubstituted isoxazoles via cope-type hydroamination of 1, 3-dialkynes. Org Lett 14(9):2418ā2421
Wang Z et al (2017b) Palladium-catalyzed 3-Aryl-5-acyl-1, 2, 4-thiadiazole formation from ketones, amidines, and sulfur powder. Eur J Org Chem 2017(12):1604ā1607
Wang ZQ et al (2018) Electrochemical synthesis of 3, 5-disubstituted-1, 2, 4-thiadiazoles through NH4I-mediated dimerization of thioamides. Adv Synth Catal 360(21):4043ā4048
Willy B, Mueller TJ (2008) Consecutive multi-component syntheses of heterocycles via palladium-copper catalyzed generation of alkynones. ARKIVOC 1:195ā208
Willy B et al (2008) Novel microwave-assisted one-pot synthesis of isoxazoles by a three-component coupling-cycloaddition sequence. Synthesis 2008(02):293ā303
Wolff L (1904) Ueber 1, 2, 3-thiodiazole. Justus Liebigs Ann Chem 333(1):1ā21
Woollins JD, Laitinen R (2011) Selenium and tellurium chemistry: from small molecules to biomolecules and materials. Springer Science & Business Media
Xie H et al (2016) A three-component approach to 3, 5-diaryl-1, 2, 4-thiadiazoles under transition-metal-free conditions. Org Lett 18(9):2196ā2199
Xie H et al (2018) Efficient synthesis of 1, 2-benzisothiazoles from o-haloarylamidines and elemental sulfur via N-S/CāS bond formation under transition-metal-free conditions. Green Chem 20(4):827ā831
Yajima K et al (2014) Facile access to 3, 5-symmetrically disubstituted 1, 2, 4-thiadiazoles through phosphovanadomolybdic acid catalyzed aerobic oxidative dimerization of primary thioamides. Chem Commun 50(51):6748ā6750
Yanagida Y et al (2011) Asymmetric synthesis of isothiazoles through cu catalysis: direct catalytic asymmetric conjugate addition of allyl cyanide to Ī±, Ī²-unsaturated thioamides. Angew Chem 123(34):8056ā8060
Yang L et al (2019) Co-catalyzed intramolecular S-N bond formation in water for 1, 2-benzisothiazol-3 (2H)-ones and 1, 2, 4-thiadiazoles synthesis. Eur J Org Chem 2019(6):1281ā1285
Yatam S et al (2018) Focused library design and synthesis of 2-mercapto benzothiazole linked 1, 2, 4-oxadiazoles as COX-2/5-LOX inhibitors. J Mol Struct 1159:193ā204
Yoshimura A et al (2013) Hypervalent iodine catalyzed generation of nitrile oxides from oximes and their cycloaddition with alkenes or alkynes. Org Lett 15(15):4010ā4013
Yoshimura A et al (2015) Preparation, structure, and versatile reactivity of pseudocyclic benziodoxole triflate, new hypervalent iodine reagent. Chem Commun 51(37):7835ā7838
Zarei M (2017) One-pot synthesis of 1, 3, 4-thiadiazoles using Vilsmeier reagent as a versatile cyclodehydration agent. Tetrahedron 73(14):1867ā1872
Zarei M (2018) A mild and efficient one-pot preparation of 1, 2, 4-oxadiazoles from nitriles and carboxylic acids using Vilsmeier reagent. ChemistrySelect 3(40):11273ā11276
Zhang D et al (2017) An iodine-mediated Hofmann-Lƶffler-Freytag reaction of sulfoximines leading to dihydroisothiazole oxides. Adv Synth Catal 359(24):4274ā4277
Zhang J et al (2018a) Synthesis and evaluation of coumarin/1, 2, 4-oxadiazole hybrids as selective BChE inhibitors with neuroprotective activity. J Asian Nat Products Res
Zhang L et al (2016) Design, synthesis and in vitro activity of phidianidine B derivatives as novel PTP1B inhibitors with specific selectivity. Bioorg Med Chem Lett 26(3):778ā781
Zhang L et al (2018b) Addition of Diazo compounds ipso-CāH bond to carbon disulfide: synthesis of 1, 2, 3-thiadiazoles under mild conditions. J Org Chem 83(7):4275ā4278
Zhou Z et al (2017) Multicomponent reactions (MCRs) of arylmethyl bromides, arylamidines and elemental sulfur toward unsymmetric 3, 5-diaryl 1, 2, 4-thiadiazoles. Tetrahedron Lett 58(26):2571ā2573
Zhou Z et al (2016) Multicomponent coupling reactions of two N-tosyl hydrazones and elemental sulfur: selective denitrogenation pathway toward unsymmetric 2, 5-disubstituted 1, 3, 4-thiadiazoles. Org Lett 18(20):5268ā5271
Zoumpoulakis P et al (2012) Synthesis of novel sulfonamide-1, 2, 4-triazoles, 1, 3, 4-thiadiazoles and 1, 3, 4-oxadiazoles, as potential antibacterial and antifungal agents. Biological evaluation and conformational analysis studies. Bioorg Med Chem 20(4):1569ā1583
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Desai, K.R., Patel, B.R. (2022). Various Synthetic Strategies and Therapeutic Potential of Thiadiazole, Oxadiazole, Isoxazole and Isothiazole Derivatives. In: Ameta, K.L., Kant, R., Penoni, A., Maspero, A., Scapinello, L. (eds) N-Heterocycles. Springer, Singapore. https://doi.org/10.1007/978-981-19-0832-3_6
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