Medicinal Chemistry Research

, Volume 27, Issue 5, pp 1309–1344 | Cite as

The synthetic and therapeutic expedition of isoxazole and its analogs

Review Paper
  • 81 Downloads

Abstract

Isoxazole, constituting an important family of five-membered heterocycles with one oxygen atom and one nitrogen atom at adjacent positions is of immense importance because of its wide spectrum of biological activities and therapeutic potential. It is, therefore, of prime importance that the development of new synthetic strategies and designing of new isoxazole derivatives should be based on the most recent knowledge emerging from the latest research. This review is an endeavor to highlight the progress in the chemistry and biological activity of isoxazole derivatives which could provide a low-height flying bird’s eye view of isoxazole derivatives to the medicinal chemists for the development of clinically viable drugs using this information.

Keywords

Heterocyclic Isoxazole Biological activity Anticancer Anti-inflammatory Antimicrobial 

Abbreviations

5-HT

5-hydroxy tryptamine

A. clavatus

Aspergillus clavatus

A. fumigates

Aspergillus fumigatus

A. niger

Aspergillus niger

AChE

Acetylcholinesterase

AR

Adrenergic receptor

B. cinerea

Botrytis cinerea

B. subtilis

Bacillus subtilis

BBB

Blood-brain barrier

C. albicans

Candida albicans

C. elegans

Caenorhabditis elegans

C. neoformans

Cryptococcus neoformans

C. tropicum

Chrysosporium tropicum

CA

Carbonic anhydrase

CDK

Cyclin-dependent kinase

CK

Casein kinase

CNS

Central nervous system

COX

Cyclooxygenase

cyt

Cytochrome

D. myceliophagus

Ditylenchus myceliophagus

DGAT

Diacylglycerol acyl transferase

DPP

Dipeptidyl peptidse

DPPH

2,2-diphenyl-1-picrylhydrazyl

E. coli

Escherichia coli

E. faecalis

Enterococcus faecalis

E. floccosum

Epidermophyton floccosum

EC

Effective concentration

ED

Effective dose

ELISA

Enzyme-linked immunosorbent assay

EPAC

Exchange proteins directly activated by cAMP

FLAP

5-lipoxygenase-activating protein

FLT

FMS-like tyrosine kinase

FRAP

Ferric-ion reducing antioxidant power

FXR

Farnesoid X receptor

GABA

γ-amino butyric acid

HDAC

Histone deacetylase

HDL

High density lipoprotein

HIV

Human immunodeficiency virus

HMEC

Human microvascular endothelial cells

Hsp

Heat shock protein

HSV

Herpes simplex virus

HTS

High-throughput screening

IC

Inhibitory concentration

JNK

c-Jun N-terminal kinase

K. pneumonia

Klebsiella pneumoniae

L. donovani

Leishmania donovani

LDL

Low density lipoprotein

LPA

Lysophosphatidic acid

mAChR

muscarinic acetylcholine receptor

MAO

Monoamine oxidase

MAP

Mitogen-activated protein

MBEC

Mouse brain endothelial cells

MES

Maximal electric shock

MIC

Minimum inhibitory concentration

MTB

Mycobacterium tuberculosis

MTT

3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide

nAChR

nicotinic acetylcholine receptor

P. aeruginosa

Pseudomonas aeruginosa

P. chrysogenum

Penicillium chrysogenum

PPAR

Peroxisome proliferator-activated receptors

PTP

Protein tyrosine phosphate

R. cerealis

Rhizoctonia cerealis

R. oryzae

Rhizopus oryzae

S. aureus

Staphylococcus aureus

S. pyogenes

Streptococcus pyogenes

S. typhi

Salmonella typhi

S. typhimurium

Salmonella typhimurium

S1P

Sphingosine-1-phosphate

SAR

Structure-activity relationship

scPTZ

subcutaneous pentylenetetrazole

SIRT

Silent information regulators

sPLA

Secretory phospholipase A

STAT

Signal transducer and activator of transcription

T. mentagrophytes

Trichophyton mentagrophytes

T. rubrum

Trichophyton rubrum

TRPM

Transient receptor potential melastatin

TRPV

Transient receptor potential vanilloid

Notes

Acknowledgements

The authors thank the authorities of GLA University, Mathura, India for their praise worthy inspiration and constant encouragement.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Abushanab E, Lee DY, Goodman L (1973) Synthetic studies in the lsoxazolo[4,5- b] pyrazine system. J Heterocycl Chem 10:181–185Google Scholar
  2. Agirbas H, Guner S, Budak F, Keceli S, Kandemirli F, Shvets N, Kovalishyn V, Dimoglo A (2007) Synthesis and structure–antibacterial activity relationship investigation of isomeric 2,3,5-substituted perhydropyrrolo[3,4-d]isoxazole-4,6-diones. Bioorg Med Chem 15:2322–2333PubMedGoogle Scholar
  3. Allegretti PA, Ferreira EM (2013) Platinum-catalyzed cyclizations viacarbene intermediates: syntheses of complementary positional isomers of isoxazoles. Chem Sci 4:1053–1058Google Scholar
  4. Almahariq M, Mei FC, Wang H, Cao AT, Yao S, Soong L, Sun J, Cong Y, Chen J, Cheng X (2015) Exchange protein directly activated by cAMP modulates regulatory T-cell-mediated immunosuppression. Biochem J 465:295–303PubMedPubMedCentralGoogle Scholar
  5. Altug C, Güneş H, Nocentini A, Monti SM, Buonanno M, Supuran CT (2017) Synthesis of isoxazole-containing sulfonamides with potent carbonic anhydrase II and VII inhibitory properties. Bioorg Med Chem 25:1456–1464PubMedGoogle Scholar
  6. Amir M, Javed SA, Kumar H (2010) Design and synthesis of 3-[3-(substituted phenyl)-4-piperidin-1-ylmethyl/-4-morpholin-4-ylmethyl-4,5-dihydro-isoxazol-5-yl]-1H-indoles as potent anti-inflammatory agents. Med Chem Res 19:299–310Google Scholar
  7. Anand P, Singh B (2012) Synthesis and evaluation of novel 4-[(3H,3aH,6aH)-3-phenyl)-4,6-dioxo-2-phenyldihydro-2H-pyrrolo[3,4-d]isoxazol-5(3H,6H,6aH)-yl]benzoic acid derivatives as potent acetylcholinesterase inhibitors and anti-amnestic agents. Bioorg Med Chem 20:521–530PubMedGoogle Scholar
  8. Andrés JI, Alcázar J, Alonso JM, Alvarez RM, Bakker MH, Biesmans I, Cid JM, De Lucas AI, Drinkenburg W, Fernández J, Font LM, Iturrino L, Langlois X, Lenaerts I, Martı́nez S, Megens AA, Pastor J, Pullan S, Steckler T (2007) Tricyclic isoxazolines: Identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and α2-adrenoceptor antagonism. Bioorg Med Chem 15:3649–3660PubMedGoogle Scholar
  9. Andrés JI, Alcázar J, Alonso JM, Alvarez RM, Cid JM, De Lucas AI, Fernández J, Martı́nez S, Nieto C, Pastor J, Bakker MH, Biesmans I, Heylen LI, Megens AA (2003) Synthesis of 3a,4-dihydro-3H-[1]benzopyrano[4,3-c]isoxazoles, displaying combined 5-HT uptake inhibiting and α2-adrenoceptor antagonistic activities: a novel series of potential antidepressants. Bioorg Med Chem Lett 13:2719–2725PubMedGoogle Scholar
  10. Andrzejak V, Millet R, Bakalia JEl, Guelzimb A, Gluszoka S, Chavattec P, Bonted J-P, Vaccher Claude, Lipka E (2010) Synthesis of 2, 3 and 4, 5-Dihydro-hydroxy-isoxazoles and Isoxazoles Under Different pH Conditions. Lett Org Chem 7:32–38Google Scholar
  11. Badru R, Anand P, Singh B (2012) Synthesis and evaluation of hexahydropyrrolo[3,4-d]isoxazole-4,6-diones as anti-stress agents. Eur J Med Chem 48:81–91PubMedGoogle Scholar
  12. Banoglu E, Çelikoglu E, Volker S, Olgac A, Gerstmeier J, Garscha U, Caliskan B, Schubert US, Carotti A, Macchiarulo A, Werz O (2016) 4,5-Diarylisoxazol-3-carboxylic acids: A new class of leukotriene biosynthesis inhibitors potentially targeting 5-lipoxygenase-activating protein (FLAP). Eur J Med Chem 113:1–10PubMedGoogle Scholar
  13. Bargiotti A, Musso L, Dallavalle S, Merlini L, Gallo G, Ciacci A, Giannini G, Cabri W, Penco S, Vesci L, Castorina M, Milazzo FM, Cervoni ML, Barbarino M, Pisano C, Giommarelli C, Zuco V, De Cesare M, Zunino F (2012) Isoxazolo(aza)naphthoquinones: A new class of cytotoxic Hsp90 inhibitors. Eur J Med Chem 53:64–75PubMedGoogle Scholar
  14. Bartzatt R (2014) Drug analogs of COX-2 selective inhibitors lumiracoxib and valdecoxib derived from in silico search and optimization. Antiinflamm Antiallergy Agents Med Chem 13:17–28PubMedGoogle Scholar
  15. Baruchello R, Simoni D, Marchetti P, Rondanin R, Mangiola S, Costantini C, Meli M, Giannini G, Vesci L, Carollo V, Brunetti T, Battistuzzi G, Tolomeo M, Cabri W (2014) 4,5,6,7-Tetrahydro-isoxazolo-[4,5-c]-pyridines as a new class of cytotoxic Hsp90 inhibitors. Eur J Med Chem 76:53–60PubMedGoogle Scholar
  16. Basha SS, Divya K, Padmaja A, Padmavathi V (2015) Synthesis and antimicrobial activity of thiazolyl pyrazoles and isoxazoles. Res Chem Intermed 41:10067–10083Google Scholar
  17. Batra S, Srinivasan T, Rastogi SK, Kundu B, Patra A, Bhaduri AP, Dixit M (2002) Combinatorial synthesis and biological evaluation of isoxazole-based libraries as antithrombotic agents. Bioorg Med Chem Lett 12:1905–19508PubMedGoogle Scholar
  18. Bourbeau MP, Rider JT (2006) A convenient synthesis of 4-alkyl-5-aminoisoxazoles. Org Lett 8:3679–3680PubMedGoogle Scholar
  19. Brahma S, Ray JK (2008) Synthesis of Azirines Containing Aldehyde Functionality and their Utilization as Synthetic Tools for Five Membered Oxazoles and Isoxazoles. J Heterocycl Chem 45:311–317Google Scholar
  20. Brahmayya M, Venkateswararao B, Krishnarao D, Durgarao S, Prasad UV, Damodharam T, Mishra R (2013) Synthesis and fungicidal activity of novel 5-aryl-4-methyl-3yl (imidazolidin-1yl methyl, 2-ylidene nitro imine) isoxazoles. J Pharm Res 7:516–519Google Scholar
  21. Bulanov DA, Novokshonova IA, Novokshonov VV, Ushakov IA, Sterkhova IV (2017) Facile one-pot synthesis of 5-substituted isoxazoles and pyrazoles via microwave- promoted intramolecular cyclization of γ-hydroxyalkynal oximes and hydrazones. Synth Commun 47:335–343Google Scholar
  22. Buoli M, Grassi S, Ciappolino V, Serati M, Altamura AC (2017) The use of zonisamide for the treatment of psychiatric disorders: A Systematic Review. Clin Neuropharmacol 40:85–92PubMedGoogle Scholar
  23. Burkhard JA, Tchitchanov BH, Carreira EM (2011) Cascade formation of isoxazoles: Facile base-mediated rearrangement of substituted oxetanes. Angew Chem–Int Ed 50:5379–5382Google Scholar
  24. Buron C, El Kaim L, Uslu A (1997) A new straightforward formation of aminoisoxazoles from isocyanides. Tetrahedron Lett 38:8027–8030Google Scholar
  25. Carroll FI, Pawlush N, Kuhar MJ, Pollard GT, Howard JL (2004) Synthesis, monoamine transporter binding properties, and behavioral pharmacology of a series of 3β-(substituted phenyl)-2β-(3ʹ-substituted isoxazol-5-yl)tropanes. J Med Chem 47:296–302PubMedGoogle Scholar
  26. Changtam C, Hongmanee P, Suksamrarn A (2010) Isoxazole analogs of curcuminoids with highly potent multidrug-resistant antimycobacterial activity. Eur J Med Chem 45:4446–4457PubMedGoogle Scholar
  27. Chavan AP, Pinjari AB, Mhaske PC (2015) An efficient synthesis of 4-arylmethylidene-3-substituted-isoxazol-5(4h)-ones in aqueous medium. J Heterocycl Chem 52:1911–1915Google Scholar
  28. Chen D, Shen A, Li J, Shi F, Chen W, Ren J, Liu H, Xu Y, Wang X, Yang X, Sun Y, Yang M, He J, Wang Y, Zhang L, Huang M, Geng M, Xiong B, Shen J (2014) Discovery of potent N-(isoxazol-5-yl)amides as HSP90 inhibitors. Eur J Med Chem 87:765–781PubMedGoogle Scholar
  29. Chikkula KV, Raja S (2017) Isoxazole-A potent pharmacophore. Int J Pharm Pharm Sci 9:13–24Google Scholar
  30. Chouaïb K, Romdhane A, Delemasure S, Dutartre P, Elie N, Touboul D, Ben jannet H, Ali Hamza M (2016) Regiospecific synthesis, anti-inflammatory and anticancer evaluation of novel 3,5-disubstituted isoxazoles from the natural maslinic and oleanolic acids. Ind Crops Prod 85:287–299Google Scholar
  31. Chundawat TS, Sharma N, Bhagat S (2014) Synthesis and in vitro antimicrobial evaluation of novel fluorine-containing 3-benzofuran-2-yl-5-phenyl-4,5-dihydro-1H-pyrazoles and 3-benzofuran-2-yl-5-phenyl-4,5-dihydro-isoxazoles. Med Chem Res 23:1350–1359Google Scholar
  32. Claisen L (1903) Zur Kenntniss des Propargylaldehyds und des Phenylpropargylaldehyds. Ber der Dtsch Chem Ges 36:3664–3673Google Scholar
  33. Clausen RP, Moltzen EK, Perregaard J, Lenz SM, Sanchez C, Falch E, Frølund B, Bolvig T, Sarup A, Larsson OM, Schousboe A, Krogsgaard-Larsen P (2005) Selective inhibitors of GABA uptake: Synthesis and molecular pharmacology of 4-N-methylamino-4,5,6,7-tetrahydrobenzo[d]isoxazol-3-ol analogues. Bioorg Med Chem 13:895–908PubMedGoogle Scholar
  34. Conti P, Roda G, Stabile H, Vanoni MA, Curti B, De Amici M (2003) Synthesis and biological evaluation of new amino acids structurally related to the antitumoragent acivicin. Farmaco 58:683–690PubMedGoogle Scholar
  35. Cronin MTD, Aptula AO, Dearden JC, Duffy JC, Netzeva TI, Patel H, Rowe PH, Schultz TW, Worth AP, Voutzoulidis K, Schüürmann G (2002) Structure-based classification of antibacterial activity. J Chem Inf Comput Sci 42:869–878PubMedGoogle Scholar
  36. Crossley JA, Browne DL (2010) An alkynyliodide cycloaddition strategy for the construction of iodoisoxazoles. J Org Chem 75:5414–5416PubMedGoogle Scholar
  37. Dallanoce C, Frigerio F, De Amici M, Dorsch S, Klotz K-N, De Micheli C (2007) Novel chiral isoxazole derivatives: Synthesis and pharmacological characterization at human β-adrenergic receptor subtypes. Bioorg Med Chem 15:2533–2543PubMedGoogle Scholar
  38. Deng B-L, Zhao Y, Hartmanb TL, Watson K, Buckheit RW, Pannecouque C, Clercq EDe, Cushmana M (2009) Synthesis of alkenyldiarylmethanes (ADAMs) containing benzo[d]isoxazole and oxazolidin-2-one rings, a new series of potent non-nucleoside HIV-1 reverse transcriptase inhibitors. Eur J Med Chem 44:1210–1214PubMedGoogle Scholar
  39. Denmark SE, Kallemeyn JM (2005) Synthesis of 3,4,5-trisubstituted isoxazoles via sequential [3 + 2] cycloaddition/silicon-based cross-coupling reactions. J Org Chem 70:2839–2842PubMedGoogle Scholar
  40. Desjardins CA, Cohen KA, Munsamy V, Abeel T, Maharaj K, Walker BJ, Shea TP, Almeida DV, Manson AL, Salazar A, Padayatchi N, O'Donnell MR, Mlisana KP, Wortman J, Birren BW, Grosset J, Earl AM, Pym AS (2016) Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance. Nat Genet 48:544–551PubMedPubMedCentralGoogle Scholar
  41. Diana P, Carbone A, Barraja P, Kelter G, Fiebig HH, Cirrincione G (2010) Synthesis and antitumor activity of 2,5-bis(3′-indolyl)-furans and 3,5-bis(3′-indolyl)-isoxazoles, nortopsentin analogues. Bioorg Med Chem 18:4524–4529PubMedGoogle Scholar
  42. Dou G, Xu P, Li Q, Xi Y, Huang Z, Shi D (2013) Clean and efficient synthesis of isoxazole derivatives in aqueous media. Molecules 18:13645–13653PubMedGoogle Scholar
  43. Eddington ND, Cox DS, Roberts RR, Butcher RJ, Edafiogho IO, Stables JP, Cooke N, Goodwin AM, Smith CA, Scott KR (2002) Synthesis and anticonvulsant activity of enaminones. 4. Investigations on isoxazole derivatives. Eur J Med Chem 37:635–648PubMedGoogle Scholar
  44. Elnagdi MH, Rifaat M, Elmoghayar H, Abdel E, Hafez A, Alnima HH (1975) Reaction of 2-Arylhydrazono-3-oxonitriles with Hydroxylamine. Synthesis of 3-Amino-4-arylazoisoxazoles. J Org Chem 40:2604–2607Google Scholar
  45. Falch E, Perregaard J, Frølund B, Søkilde B, Buur A, Hansen LM, Frydenvang K, Brehm L, Bolvig T, Larsson OM, Sanchez C, White HS, Schousboe A, Krogsgaard-Larsen P (1999) Selective inhibitors of glial gaba uptake: synthesis, absolute stereochemistry, and pharmacology of the enantiomers of 3-hydroxy-4-amino-4,5,6,7-tetrahydro-1,2-benzisoxazole (exo-THPO) and analogues. J Med Chem 42:5402–5414PubMedGoogle Scholar
  46. Frølund B, Jensen LS, Storustovu SI, Stensbøl TB, Ebert B, Kehler J, Krogsgaard-Larsen P, Liljefors T (2007) 4-Aryl-5-(4-piperidyl)-3-isoxazolol GABA A antagonists: synthesis, pharmacology, and structure−activity relationships. J Med Chem 50:1988–1992PubMedGoogle Scholar
  47. Gautam KC, Singh DP (2013) Synthesis and antimicrobial activity of some isoxazole derivatives of thiophene. Chem Sci Trans 2:992–996Google Scholar
  48. Gayon E, Quinonero O, Lemouzy S, Vrancken E, Campagne JM (2011) Transition-metal-catalyzed uninterrupted four-step sequence to access trisubstituted isoxazoles. Org Lett 13:6418–6421PubMedGoogle Scholar
  49. Genc Y, Ozkanca R, Bekdemir Y (2008) An overview on some benzimidazole and sulfonamide derivatives with anti-microbial activity. Ann Clin Microbiol Antimicrob 7:17–25PubMedPubMedCentralGoogle Scholar
  50. Genin MJ, Bueno AB, Agejas Francisco J, Manninen PR, Bocchinfuso WP, Montrose-Rafizadeh C, Cannady EA, Jones TM, Stille JR, Raddad E, Reidy C, Cox A, Michael MD, Michael LF (2015) Discovery of 6-(4-{[5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl]methoxy}piperidin-1-yl)-1-methyl-1H -indole-3-carboxylic Acid: A Novel FXR Agonist for the treatment of dyslipidemia. J Med Chem 58:9768–9772PubMedGoogle Scholar
  51. Giustina A, Malerba M, Bresciani E, Desenzani P, Licini M, Zaltieri G, Grassi V (1995) Effect of two beta 2-agonist drugs, salbutamol and broxaterol, on the growth hormone response to exercise in adult patients with asthmatic bronchitis. J Endocrinol Invest 18:847–852PubMedGoogle Scholar
  52. Golicki D, Newada M, Lis J, Pol K, Hermanowski T, Tłustochowicz M (2012) Leflunomide in monotherapy of rheumatoid arthritis: meta-analysis of randomized trials. Pol Arch Med Wewn 122:22–32PubMedGoogle Scholar
  53. Guo S, Wang J, Zhang X, Cojean S, Loiseau PM, Fan X (2015) Synthesis of 5-isoxazol-3-yl-pyrimidine nucleosides as potential antileishmanial agents. Bioorg Med Chem Lett 25:2617–2620PubMedGoogle Scholar
  54. Gutiérrez M, Matus MF, Poblete T, Amigo J, Vallejos G, Astudillo L (2013) Isoxazoles: synthesis, evaluation and bioinformatic design as acetylcholinesterase inhibitors. J Pharm Pharmacol 65:1796–1804PubMedGoogle Scholar
  55. Habeeb AG, Praveen Rao PN, Knaus EE (2001) Design and synthesis of 4,5-diphenyl-4-isoxazolines: Novel inhibitors of cyclooxygenase-2 with analgesic and antiinflammatory activity. J Med Chem 44:2921–2927PubMedGoogle Scholar
  56. Hansen TV, Wu P, Fokin VV (2005) One-Pot Copper(I)-Catalyzed Synthesis of 3,5-Disubstituted Isoxazoles. J Org Chem 70:7761–7764PubMedGoogle Scholar
  57. Harigae R, Moriyama K, Togo H (2014) Preparation of 3,5-disubstituted pyrazoles and isoxazoles from terminal alkynes, aldehydes, hydrazines, and hydroxylamine. J Org Chem 79:2049–2058PubMedGoogle Scholar
  58. He Y, Duckett D, Chen W, Ling YY, Cameron MD, Lin L, Ruiz CH, Lograsso PV, Kamenecka TM, Koenig M (2014) Synthesis and SAR of novel isoxazoles as potent c-jun N-terminal kinase (JNK) inhibitors. Bioorg Med Chem Lett 24:161–164PubMedGoogle Scholar
  59. Hu F, Szostak M (2015) Recent developments in the synthesis and reactivity of isoxazoles: metal catalysis and beyond. Adv Synth Catal 357:2583–2614Google Scholar
  60. Huang M, Suk D-H, Cho N-C, Bhattarai D, Kang SB, Kim Y, Pae AN, Rhim H, Keum G (2015) Synthesis and biological evaluation of isoxazoline derivatives as potent M1 muscarinic acetylcholine receptor agonists. Bioorg Med Chem Lett 25:1546–1551PubMedGoogle Scholar
  61. Huang Z-B, Li L-L, Zhao Y-W, Wang H-Y, Shi D-Q (2014) An efficient synthesis of isoxazoles and pyrazoles under ultrasound irradiation. J Heterocycl Chem 51:E309–E313Google Scholar
  62. Im D, Jung K, Yang S, Aman W, Hah JM (2015) Discovery of 4-arylamido 3-methyl isoxazole derivatives as novel FMS kinase inhibitors. Eur J Med Chem 102:600–610PubMedGoogle Scholar
  63. Jadhav RD, Kadam KS, Kandre S, Guha T, Reddy MMK, Brahma MK, Deshmukh NJ, Dixit A, Doshi L, Potdar N, Enose AA, Vishwakarma RA, Sivaramakrishnan H, Srinivasan S, Nemmani KVS, Gupte A, Gangopadhyay AK, Sharma R (2012) Synthesis and biological evaluation of isoxazole, oxazole, and oxadiazole containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors. Eur J Med Chem 54:324–342PubMedGoogle Scholar
  64. Jadhav RD, Mistry HD, Motiwala H, Kadam KS, Kandre S, Gupte A, Gangopadhyay AK, Sharma R (2013) A facile one-pot synthesis of 3,5-disubstituted isoxazole derivatives using hydroxy (tosyloxy) iodobenzene. J Heterocycl Chem 50:774–780Google Scholar
  65. Jeong Y, Kim B, Lee JK, Ryu J (2014) Direct synthesis of 4-fluoroisoxazoles through gold-catalyzed cascade cyclization–fluorination of 2-alkynone O-methyl oximes. J Org Chem 79:6444–6455PubMedGoogle Scholar
  66. Ji S, Hong WP, Ko SH, Lee K (2006) The dipolar route to naphtho[2,1-c] isoxazoles from the Baylis-Hillman adducts of 2-alkynylbenzaldehydes. J Heterocycl Chem 43:799–801Google Scholar
  67. Jiang X, Liu H, Song Z, Peng X, Ji Y, Yao Q, Geng M, Ai J, Zhang A (2015) Discovery and SAR study of c-Met kinase inhibitors bearing an 3-amino-benzo[d]isoxazole or 3-aminoindazole scaffold. Bioorg Med Chem 23:564–578PubMedGoogle Scholar
  68. Jin C, Navarro Ha, Page K, Carroll FI (2008) Synthesis and monoamine transporter binding properties of 2beta-[3’-(substituted benzyl)isoxazol-5-yl]- and 2beta-[3’-methyl-4’-(substituted phenyl)isoxazol-5-yl]-3beta-(substituted phenyl)tropanes. Bioorg Med Chem 16:6682–6688PubMedPubMedCentralGoogle Scholar
  69. Joshi SD, Dixit SR, Kirankumar MN, Aminabhavi TM, Raju KVSN, Narayan R, Lherbet C, Yang KS (2016) Synthesis, antimycobacterial screening and ligand-based molecular docking studies on novel pyrrole derivatives bearing pyrazoline, isoxazole and phenyl thiourea moieties. Eur J Med Chem 107:133–152PubMedGoogle Scholar
  70. Kachhadia VV, Patel MR, Joshi HS (2004) Synthesis of isoxazoles and cyanopyridines bearing benzo (b) thiophene nucleus as potential antitubercular and antimicrobial agents. J Sci Islam Repub Iran 15:47–51Google Scholar
  71. Kafle B, Aher NG, Khadka D, Park H, Cho H (2011) Isoxazol-5(4H)one derivatives as PTP1B inhibitors showing an anti-obesity effect. Chem - Asian J 6:2073–2079PubMedGoogle Scholar
  72. Kafle B, Cho H (2012) Isoxazolone derivatives as potent inhibitors of PTP1B. Bull Korean Chem Soc 33:275–277Google Scholar
  73. Kalirajan R, Rafick MHM, Sankar S, Jubie S (2012) Docking studies, synthesis, characterization and evaluation of their antioxidant and cytotoxic activities of some novel isoxazole-substituted 9-anilinoacridine derivatives. Sci World J 2012:1–6Google Scholar
  74. Kamal A, Bharathi EV, Reddy JS, Ramaiah MJ, Dastagiri D, Reddy MK, Viswanath A, Reddy TL, Shaik TB, Pushpavalli SNCVL, Bhadra MP (2011) Synthesis and biological evaluation of 3,5-diaryl isoxazoline/isoxazole linked 2,3-dihydroquinazolinone hybrids as anticancer agents. Eur J Med Chem 46:691–703PubMedGoogle Scholar
  75. Kamal A, Surendranadha Reddy J, Janaki Ramaiah M, Dastagiri D, Vijaya Bharathi E, Ameruddin Azhar M, Sultana F, Pushpavalli SNCVL, Pal-Bhadra M, Juvekar A (2010) Design, synthesis and biological evaluation of 3,5-diaryl-isoxazoline/isoxazole-pyrrolobenzodiazepine conjugates as potential anticancer agents. Eur J Med Chem 45:3924–3937PubMedGoogle Scholar
  76. Karthikeyan K, Veenus Seelan T, Lalitha KG, Perumal PT (2009) Synthesis and antinociceptive activity of pyrazolyl isoxazolines and pyrazolyl isoxazoles. Bioorg Med Chem Lett 19:3370–3373PubMedGoogle Scholar
  77. Kesornpun C, Aree T, Mahidol C, Ruchirawat S, Kittakoop P (2016) Corrigendum: water-assisted nitrile oxide cycloadditions: synthesis of isoxazoles and stereoselective syntheses of isoxazolines and 1,2,4-oxadiazoles. Angew Chem Int Ed 55:10548–10548Google Scholar
  78. Kiyani H (2013) Synthesis of 4-arylmethylidene-3-methyl-isoxazol-5(4H)-ones via a three-component reaction in water catalyzed by sodium ascorbate. Org Chem Indian J 9:97–101Google Scholar
  79. Kiyani H, Ghorbani F (2013a) Synthesis of arylmethylidene-isoxazole-5(4H)-ones in water catalyzed by sodium citrate. Heterocycl Lett 3:145–153Google Scholar
  80. Kiyani H, Ghorbani F (2013b) Synthesis of arylmethylidene-isoxazol-5(4H)-ones via three-component reaction in water catalyzed by sodium tetraborate. Open J Org Chem 1:5–9Google Scholar
  81. Kiyani H, Ghorbani F (2013c) Synthesis of 4-arylmethyleneisoxazole-5-one derivatives via a one-pot three-component reaction in water catalyzed by sodium azide. Elixir Org Chem 58A:14948–14950Google Scholar
  82. Kiyani H, Ghorbani F (2013d) Potassium phthalimide as efficient basic organocatalyst for the synthesis of 3A4-disubstituted isoxazol-5a4Ha-ones in aqueous medium. J Saudi Chem Soc 21:S112–S119Google Scholar
  83. Kiyani H, Ghorbani F (2013e) Sodium saccharin as a clean and efficient catalyst for the synthesis of 4-arylidene-3-methylisoxazol-5(4H)-ones via one-pot three-component reaction in aqueous medium. Heterocycl Lett 3:359–369Google Scholar
  84. Kiyani H, Ghorbani F (2015) Boric acid-catalyzed multi-component reaction for efficient synthesis of 4H-isoxazol-5-ones in aqueous medium. Res Chem Intermed 41:2653–2664Google Scholar
  85. Kiyani H, Kanaani A, Ajloo D, Ghorbani F, Vakili M (2015) N-bromosuccinimide(NBS)-promoted, three-component synthesis of α,β-unsaturated isoxazol-5(4H)-ones, and spectroscopic investigation and computational study of 3-methyl-4-(thiophen-2-ylmethylene)isoxazol-5(4H)-one. Res Chem Intermed 41:7739–7773Google Scholar
  86. Koufaki M, Fotopoulou T, Kapetanou M, Heropoulos GA, Gonos ES, Chondrogianni N (2014) Microwave-assisted synthesis of 3,5-disubstituted isoxazoles and evaluation of their anti-ageing activity. Eur J Med Chem 83:508–515PubMedGoogle Scholar
  87. Koufaki M, Tsatsaroni A, Alexi X, Guerrand H, Zerva S, Alexis MN (2011) Isoxazole substituted chromans against oxidative stress-induced neuronal damage. Bioorg Med Chem 19:4841–4850PubMedGoogle Scholar
  88. Kumar A, Maurya RA, Sharma S, Ahmad P, Singh AB, Tamrakar AK, Srivastava AK (2009) Design and synthesis of 3,5-diarylisoxazole derivatives as novel class of anti-hyperglycemic and lipid lowering agents. Bioorg Med Chem 17:5285–5292PubMedGoogle Scholar
  89. Kumar J, Chawla G, Akhtar M, Sahu K, Rathore V, Sahu S (2017) Design, synthesis and pharmacological evaluation of some novel derivatives of 1-{[3-(furan-2-yl)-5-phenyl-4,5-dihydro-1,2-oxazol-4-yl]methyl}-4-methyl piperazine. Arab J Chem 10:141–149Google Scholar
  90. Kumbhare RM, Kosurkar UB, Janaki Ramaiah M, Dadmal TL, Pushpavalli SNCVL, Pal-Bhadra M (2012) Synthesis and biological evaluation of novel triazoles and isoxazoles linked 2-phenyl benzothiazole as potential anticancer agents. Bioorg Med Chem Lett 22:5424–5427PubMedGoogle Scholar
  91. Lainson JC, Daly SM, Triplett K, Johnston SA, Hall PR, Diehnelt CW (2017) Synthetic antibacterial peptide exhibits synergy with Oxacillin against MRSA. ACS Med Chem Lett 8:853–857PubMedGoogle Scholar
  92. Lasri J, Mukhopadhyay S, Charmier MAJ (2008) Efficient regioselective synthesis of 4- and 5-substituted isoxazoles under thermal and microwave conditions. J Heterocycl Chem 45:1385–1389Google Scholar
  93. Laufer SA, Margutti S, Fritz MD (2006) Substituted isoxazoles as potent inhibitors of p38 MAP kinase. ChemMedChem 1:197–207PubMedGoogle Scholar
  94. Lavanya G, Mallikarjuna Reddy L, Padmavathi V, Padmaja A (2014) Synthesis and antimicrobial activity of (1,4-phenylene)bis(arylsulfonylpyrazoles and isoxazoles). Eur J Med Chem 73:187–194PubMedGoogle Scholar
  95. Lee YS, Park SM, Kim BH (2009) Synthesis of 5-isoxazol-5-yl-2′-deoxyuridines exhibiting antiviral activity against HSV and several RNA viruses. Bioorg Med Chem Lett 19:1126–1128PubMedGoogle Scholar
  96. Lehtonen K, Summers LA, Carter GA (1972) Fungitoxicity of acid and alkali hydrolysis products of Drazoxolon and related arylhydrazonoisoxazolones. Pestic Sci 3:357–364Google Scholar
  97. Li Y, Gao M, Liu B, Xu B (2017) Copper nitrate-mediated chemo- and regioselective annulation from two different alkynes: a direct route to isoxazoles. Org Chem Front 4:445–449Google Scholar
  98. Liu F, Wang M, Teng X, Zhang P, Jiang L (2014) Synthesis and biological evaluation of novel 2-(substituted isoxazol-4-yl)-5-arylamino-1,3,4-oxadiazoles. Res Chem Intermed 40:1575–1581Google Scholar
  99. Liu J, Yu LF, Eaton JB, Caldarone B, Cavino K, Ruiz C, Terry M, Fedolak A, Wang D, Ghavami A, Lowe DA, Brunner D, Lukas RJ, Kozikowski AP (2011) Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression. J Med Chem 54:7280–7288PubMedPubMedCentralGoogle Scholar
  100. Liu T, Dong X, Xue N, Wu R, He Q, Yang B, Hu Y (2009) Synthesis and biological evaluation of 3,4-diaryl-5-aminoisoxazole derivatives. Bioorg Med Chem 17:6279–6285PubMedGoogle Scholar
  101. Machetti F, Cecchi L, Trogu E, De Sarlo F (2007) Isoxazoles and isoxazolines by 1,3-dipolar cycloaddition: base-catalysed condensation of primary nitro compounds with dipolarophiles. Eur J Org Chem 2007:4352–4359Google Scholar
  102. Mahajan SS, Scian M, Sripathy S, Posakony J, Lao U, Loe TK, Leko V, Thalhofer A, Schuler AD, Bedalov A, Simon JA (2014) Development of pyrazolone and isoxazol-5-one cambinol analogues as sirtuin inhibitors. J Med Chem 57:3283–3294PubMedPubMedCentralGoogle Scholar
  103. Majewsky M, Wagner D, Delay M, Bräse S, Yargeau V, Horn H (2014) Antibacterial activity of sulfamethoxazole transformation products (TPs): general relevance for sulfonamide TPs modified at the para position. Chem Res Toxicol 27:1821–1828PubMedGoogle Scholar
  104. Malik S, Ahuja P, Sahu K, Khan SA (2014) Design and synthesis of new of 3-(benzo[d]isoxazol-3-yl)-1-substituted pyrrolidine-2,5-dione derivatives as anticonvulsants. Eur J Med Chem 84:42–50PubMedGoogle Scholar
  105. Malik S, Khan SA (2014) Design and synthesis of (5-amino-1, 2, 4-triazin-6-yl)(2-(benzo[d] isoxazol-3-yl) pyrrolidin-1-yl)methanone derivatives as sodium channel blocker and anticonvulsant agents. J Enzym Inhib Med Chem 29:505–516Google Scholar
  106. Mani SSR, Iyyadurai R (2017) Cloxacillin induced agranulocytosis: a rare adverse event of a commonly used antibiotic. Int J Immunopathol Pharmacol 30:297–301PubMedPubMedCentralGoogle Scholar
  107. Manna K, Banik U, Ghosh PS, Das M (2014) A review on synthesis and pharmacological diversity of isoxazoles & pyrazolines. Nirma Univ J Pharm Sci 1:37–49Google Scholar
  108. Mao J, Yuan H, Wang Y, Wan B, Pak D, He R, Franzblau SG (2010) Synthesis and antituberculosis activity of novel mefloquine-isoxazole carboxylic esters as prodrugs. Bioorg Med Chem Lett 20:1263–1268PubMedGoogle Scholar
  109. Mares D, Romagnoli C, Tosi B, Benvegnù R, Bruni A, Vicentini CB (2002) Mannan changes induced by 3-methyl-5-aminoisoxazole-4-thiocyanate, a new azole derivative, on Epidermophyton floccosum. Fungal Genet Biol 36:47–57PubMedGoogle Scholar
  110. Martins MAP, Flores AFC, Bastos GP, Sinhorin A, Bonacorso HG, Zanatta N (2000) A convenient one-pot synthesis of 5-carboxyisoxazoles: Trichloromethyl group as a carboxyl group precursor. Tetrahedron Lett 41:293–297Google Scholar
  111. Maurya R, Ahmad A, Gupta P, Chand K, Kumar M, Jayendra, Rawat P, Rasheed N, Palit G (2011) Synthesis of novel isoxazolines via 1,3-dipolar cycloaddition and evaluation of anti-stress activity. Med Chem Res 20:139–145Google Scholar
  112. Mazimba O, Wale K, Loeto D, Kwape T (2014) Antioxidant and antimicrobial studies on fused-ring pyrazolones and isoxazolones. Bioorg Med Chem 22:6564–6569PubMedGoogle Scholar
  113. McKinney AR, Cawley AT, Young EB, Kerwick CM, Cunnington K, Stewart RT, Ambrus JI, Willis AC, McLeod MD (2013) The metabolism of anabolic-androgenic steroids in the greyhound. Bioanalysis 5:769–781PubMedGoogle Scholar
  114. Md Tohid SF, Ziedan NI, Stefanelli F, Fogli S, Westwell AD (2012) Synthesis and evaluation of indole-containing 3,5-diarylisoxazoles as potential pro-apoptotic antitumour agents. Eur J Med Chem 56:263–270PubMedGoogle Scholar
  115. Meleddu R, Distinto S, Cirilli R, Alcaro S, Yanez M, Sanna ML, Corona A, Melis C, Bianco G, Matyus P, Cottiglia F, Maccioni E (2017) Through scaffold modification to 3,5-diaryl-4,5-dihydroisoxazoles: new potent and selective inhibitors of monoamine oxidase B. J Enzym Inhib Med Chem 32:264–270Google Scholar
  116. Mohammed S, Vishwakarma RA, Bharate SB (2015) Metal-free DBU promoted regioselective synthesis of isoxazoles and isoxazolines. RSC Adv 5:3470–3473Google Scholar
  117. Mokale SN, Nevase MC, Sakle NS, Dube PN, Shelke VR, Bhavale SA, Begum A (2014) Synthesis and in-vivo hypolipidemic activity of some novel substituted phenyl isoxazol phenoxy acetic acid derivatives. Bioorg Med Chem Lett 24:2155–2158PubMedGoogle Scholar
  118. Naidu KM, Suresh A, Subbalakshmi J, Sriram D, Yogeeswari P, Raghavaiah P, Chandra Sekhar KVG (2014) Design, synthesis and antimycobacterial activity of various 3-(4-(substituted sulfonyl)piperazin-1-yl)benzo[d]isoxazole derivatives. Eur J Med Chem 87:71–78PubMedGoogle Scholar
  119. Najafi Z, Mahdavi M, Safavi M, Saeedi M, Alinezhad H, Pordeli M, Kabudanian Ardestani S, Shafiee A, Foroumadi A, Akbarzadeh T (2015) Synthesis and in vitro cytotoxic activity of novel triazole-isoxazole derivatives. J Heterocycl Chem 52:1743–1747Google Scholar
  120. Nenajdenko VG, Zakurdaev EP, Gololobov AM, Balenkova ES (2005) Synthesis of 5-substituted 4-aminoalkylpyrazol-3-ones (isoxazol-3-ones) from 3-acyllactams. Russ Chem Bull 54:220–225Google Scholar
  121. Oakdale JS, Sit RK, Fokin VV (2014) Ruthenium-catalyzed cycloadditions of 1-haloalkynes with nitrile oxides and organic azides: synthesis of 4-haloisoxazoles and 5-halotriazoles. Chem-A Eur J 20:11101–11110Google Scholar
  122. Olesen PH, Swedberg MDB, Rimvall K (1998) 3-(5-Alkylamino-4-isoxazolyl)-1,2,5,6-tetrahydropyridines: a novel class of central nicotinic receptor ligands. Bioorg Med Chem 6:1623–1629PubMedGoogle Scholar
  123. Ostacolo C, Ambrosino P, Russo R, Lo Monte M, Soldovieri MV, Laneri S, Sacchi A, Vistoli G, Taglialatela M, Calignano A (2013) Isoxazole derivatives as potent transient receptor potential melastatin type 8 (TRPM8) agonists. Eur J Med Chem 69:659–669PubMedGoogle Scholar
  124. Özkay Y, İncesu Z, Önder Nİ, Tunalı Y, Karaca H, Işıkdağ İ, Uçucu Ü (2013) Antimicrobial and anticancer effects of some 2-(substitutedsulfanyl)-N-(5-methyl-isoxazol-3-yl)acetamide derivatives. Med Chem Res 22:211–218Google Scholar
  125. Padmaja A, Payani T, Reddy GD, Padmavathi V (2009) Synthesis, antimicrobial and antioxidant activities of substituted pyrazoles, isoxazoles, pyrimidine and thioxopyrimidine derivatives. Eur J Med Chem 44:4557–4566PubMedGoogle Scholar
  126. Padmaja A, Rajasekhar C, Muralikrishna A, Padmavathi V (2011) Synthesis and antioxidant activity of oxazolyl/thiazolylsulfonylmethyl pyrazoles and isoxazoles. Eur J Med Chem 46:5034–5038PubMedGoogle Scholar
  127. Palin R, Abernethy L, Ansari N, Cameron K, Clarkson T, Dempster M, Dunn D, Easson AM, Edwards D, MacLean J, Everett K, Feilden H, Ho KK, Kultgen S, Littlewood P, McArthur D, McGregor D, McLuskey H, Neagu I, Neale S, Nisbet LA, Ohlmeyer M, Pham Q, Ratcliffe P, Rong Y, Roughton A, Sammons M, Swanson R, Tracey H, Walker G (2011) Structure-activity studies of a novel series of isoxazole-3-carboxamide derivatives as TRPV1 antagonists. Bioorg Med Chem Lett 21:892–898PubMedGoogle Scholar
  128. Panathur N, Gokhale N, Dalimba U, Koushik PV, Yogeeswari P, Sriram D (2015) New indole-isoxazolone derivatives: Synthesis, characterisation and in vitro SIRT1 inhibition studies. Bioorg Med Chem Lett 25:2768–2772PubMedGoogle Scholar
  129. Panda S, Chowdary P, Jayashree B (2009) Synthesis, antiinflammatory and antibacterial activity of novel indolyl-isoxazoles. Indian J Pharm Sci 71:684–687PubMedPubMedCentralGoogle Scholar
  130. Patel D, Kumari P, Patel NB (2014) Synthesis and biological evaluation of coumarin based isoxazoles, pyrimidinthiones and pyrimidin-2-ones. Arab J Chem 10:S3990–S4001Google Scholar
  131. Patil PO, Bari SB (2013) Synthesis and Antidepressant activity of some new 5-(1H-indol-3-yl)-3-(substituted aryl)-4,5-dihydroisoxazoline derivatives. J Chem 2013:1–8Google Scholar
  132. Pedada SR, Yarla NS, Tambade PJ, Dhananjaya BL, Bishayee A, Arunasree KM, Philip GH, Dharmapuri G, Aliev G, Putta S, Rangaiah G (2016) Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents. Eur J Med Chem 112:289–297PubMedGoogle Scholar
  133. Peifer C, Abadleh M, Bischof J, Hauser D, Schattel V, Hirner H, Knippschild U, Laufer S (2009) 3,4-Diaryl-isoxazoles and -imidazoles as potent dual inhibitors of p38α mitogen activated protein kinase and casein kinase 1δ. J Med Chem 52:7618–7630PubMedGoogle Scholar
  134. Peifer C, Wagner G, Laufer S (2006) New approaches to the treatment of inflammatory disorders small molecule inhibitors of p38 MAP kinase. Curr Top Med Chem 6:113–149PubMedGoogle Scholar
  135. Peng-fei L, Ji-feng Z, Tao Y, Li-xia X, Zheng-ming LI (2012) Design, synthesis and insecticidal activities of novel phenyl substituted isoxazolecarboxamides. Chem Res Chin Univ 28:430–433Google Scholar
  136. Pérez JM, Ramón DJ (2015) Synthesis of 3,5-disubstituted isoxazoles and isoxazolines in deep eutectic solvents. ACS Sustain. Chem Eng 3:2343–2349Google Scholar
  137. Perrone MG, Vitale P, Panella A, Ferorelli S, Contino M, Lavecchia A, Scilimati A (2016) Isoxazole-based-scaffold inhibitors targeting cyclooxygenases (COXs). ChemMedChem 11:1172–1187PubMedGoogle Scholar
  138. Rajanarendar E, Rama Krishna S, Nagaraju D, Govardhan Reddy K, Kishore B, Reddy YN (2015) Environmentally benign synthesis, molecular properties prediction and anti-inflammatory activity of novel isoxazolo[5,4-d]isoxazol-3-yl-aryl-methanones via vinylogous Henry nitroaldol adducts as synthons. Bioorg Med Chem Lett 25:1630–1634PubMedGoogle Scholar
  139. Raji Reddy C, Vijaykumar J, Jithender E, Reddy GPK, Gree R (2012) One-pot synthesis of 3,5-disubstituted isoxazoles from propargylic alcohols through propargylic N -hydroxylamines. Eur J Org Chem 2012:5767–5773Google Scholar
  140. Rakesh SD, Lee RB, Tangallapally RP, Lee RE (2009) Synthesis, optimization and structure-activity relationships of 3,5-disubstituted isoxazolines as new anti-tuberculosis agents. Eur J Med Chem 44:460–472PubMedGoogle Scholar
  141. RamaRao RJ, Rao AKSB, Sreenivas N, Kumar BS, Murthy YLN (2011) Synthesis and antibacterial activity of novel 5-(heteroaryl)isoxazole Derivatives. J Korean Chem Soc 55:243–250Google Scholar
  142. Ratnakar Reddy K, Sambasiva Rao P, Jitender Dev G, Poornachandra Y, Ganesh Kumar C, Shanthan Rao P, Narsaiah B (2014) Synthesis of novel 1,2,3-triazole/isoxazole functionalized 2H-Chromene derivatives and their cytotoxic activity. Bioorg Med Chem Lett 24:1661–1663PubMedGoogle Scholar
  143. Sahu S, Banerjee M, Sahu D, Behera C, Pradhan G, Azam MA (2009) Synthesis, analgesic and antimicrobial activities of some novel isoxazole derivatives. Dhaka Univ J Pharm Sci 7:113–118Google Scholar
  144. Samai S, Chanda T, Ila H, Singh MS (2013) One-Pot Three-component heteroannulation of β-oxo dithioesters, amines and hydroxylamine: regioselective, facile and straightforward entry to 5-substituted 3-aminoisoxazoles. Eur J Org Chem 2013:4026–4031Google Scholar
  145. Sambasiva Rao P, Kurumurthy C, Veeraswamy B, Poornachandra Y, Ganesh Kumar C, Narsaiah B (2014) Synthesis of novel 5-(3-alkylquinolin-2-yl)-3-aryl isoxazole derivatives and their cytotoxic activity. Bioorg Med Chem Lett 24:1349–1351PubMedGoogle Scholar
  146. Schoretsanitis G, Spina E, Hiemke C, de Leon J (2017) A systematic review and combined analysis of therapeutic drug monitoring studies for long-acting risperidone. Expert Rev Clin Pharmacol 10:965–981PubMedGoogle Scholar
  147. Shader RI, Greenblatt DJ (1999) The reappearance of a monamine oxidase inhibitor (isocarboxazid). J Clin Psychopharmacol 19:105–106PubMedGoogle Scholar
  148. Shailaja M, Manjula A, Rao BV, Praseeda B, Reddy BM (2011) Synthesis of novel 3, 5-disubstituted-4,5-dihydroisoxazoles and 3,4,5- trisubstituted isoxazoles and their biological activity. Indian J Chem - Sect B Org Med Chem 50:214–222Google Scholar
  149. Shakeel-u-Rehman M-ur-R, Tripathi VK, Singh J, Ara T, Koul S, Farooq S, Kaul A (2014) Synthesis and biological evaluation of novel isoxazoles and triazoles linked 6-hydroxycoumarin as potent cytotoxic agents. Bioorg Med Chem Lett 24:4243–4246PubMedGoogle Scholar
  150. Shaw J, Chen B, Bourgault JP, Jiang H, Kumar N, Mishra J, Valeriote FA, Media J, Bobbitt K, Pietraszkiewicz H, Edelstein M, Andreana PR (2012) Synthesis and biological evaluation of novel N-phenyl-5-carboxamidyl isoxazoles as potential chemotherapeutic agents for colon cancer. Am J Biomed Sci 4:14–25PubMedPubMedCentralGoogle Scholar
  151. Sherin DR, Rajashekharan KN (2016) Curcuminoid-derived 3,5-bis(styryl)isoxazoles - mechanochemical synthesis and antioxidant activity. J Chem Sci 128:1315–1319Google Scholar
  152. Shin JH, Gadde KM, Østbye T, Bray GA (2014) Weight changes in obese adults 6-months after discontinuation of double-blind zonisamide or placebo treatment. Diabetes Obes Metab 16:766–768PubMedPubMedCentralGoogle Scholar
  153. Siddiqui N, Idrees M, Khati NT, Dhonde MG (2013) Synthesis and antimicrobial activities of some new pyrazoles, oxadiazoles and isoxazole bearing benzofuran moiety. South Afr J Chem 66:248–253Google Scholar
  154. Silva NM, Tributino JLM, Miranda ALP, Barreiro EJ, Fraga CAM (2002) New isoxazole derivatives designed as nicotinic acetylcholine receptor ligand candidates. Eur J Med Chem 37:163–170PubMedGoogle Scholar
  155. Simoni D, Roberti M, Invidiata FP, Rondanin R, Baruchello R, Malagutti C, Mazzali A, Rossi M, Grimaudo S, Capone F, Dusonchet L, Meli M, Raimondi MV, Landino M, D’Alessandro N, Tolomeo M, Arindam D, Lu S, Benbrook DM (2001) Heterocycle-Containing Retinoids. Discovery of a novel isoxazole arotinoid possessing potent apoptotic activity in multidrug and drug-induced apoptosis-resistant cells. J Med Chem 44:2308–2318PubMedGoogle Scholar
  156. Srinivas A, Nagaraj A, Reddy CS (2010) Synthesis and in vitro study of methylene-bis-tetrahydro[1,3]thiazolo[4,5-c]isoxazoles as potential nematicidal agents. Eur J Med Chem 45:2353–2358PubMedGoogle Scholar
  157. Srinivas A, Nagaraj A, Sanjeeva Reddy C (2009) Synthesis and in vitro study of a new class of methylene-bis-4,6-diarylbenzo[d]isoxazoles as potential antifungal agents. J Heterocycl Chem 46:497–502Google Scholar
  158. Sysak A, Obmińska-Mrukowicz B (2017) Isoxazole ring as a useful scaffold in a search for new therapeutic agents. Eur J Med Chem 137:292–309PubMedGoogle Scholar
  159. Trogu E, Vinattieri C, De Sarlo F, Machetti F (2012) Acid-base-catalysed condensation reaction in water: Isoxazolines and isoxazoles from nitroacetates and dipolarophiles. Chem–A Eur J 18:2081–2093Google Scholar
  160. Tzanetou E, Liekens S, Kasiotis KM, Melagraki G, Afantitis A, Fokialakis N, Haroutounian SA (2014) Antiproliferative novel isoxazoles: Modeling, virtual screening, synthesis, and bioactivity evaluation. Eur J Med Chem 81:139–149PubMedGoogle Scholar
  161. Vaidya SD, Kumar BVS, Kumar RV, Bhise UN, Mashelkar UC (2007) Synthesis, anti-bacterial, anti-asthmatic and anti-diabetic activities of novel N -substituted-2-(benzo[d]isoxazol-3-ylmethyl)-1H-benzimidazoles. J Heterocycl Chem 44:685–691Google Scholar
  162. Valizadeh H, Amiri M, Gholipur H (2009) Efficient and convenient method for the synthesis of isoxazoles in ionic liquid. J Heterocycl Chem 46:108–110Google Scholar
  163. Verma A, Wong DM, Islam R, Tong F, Ghavami M, Mutunga JM, Slebodnick C, Li J, Viayna E, Lam PC-H, Totrov MM, Bloomquist JR, Carlier PR (2015) 3-Oxoisoxazole-2(3H)-carboxamides and isoxazol-3-yl carbamates: Resistance-breaking acetylcholinesterase inhibitors targeting the malaria mosquito, Anopheles gambiae. Bioorg Med Chem 23:1321–1340PubMedPubMedCentralGoogle Scholar
  164. Vitale P, Perrone MG, Malerba P, Lavecchia A, Scilimati A (2014) Selective COX-1 inhibition as a target of theranostic novel diarylisoxazoles. Eur J Med Chem 74:606–618PubMedGoogle Scholar
  165. Vitale P, Tacconelli S, Perrone MG, Malerba P, Simone L, Scilimati A, Lavecchia A, Dovizio M, Marcantoni E, Bruno A, Patrignani P (2013) Synthesis, pharmacological characterization, and docking analysis of a novel family of diarylisoxazoles as highly selective cyclooxygenase-1 (COX-1) inhibitors. J Med Chem 56:4277–4299PubMedGoogle Scholar
  166. Wagner E, Al-Kadasi K, Zimecki M, Sawka-Dobrowolska W (2008) Synthesis and pharmacological screening of derivatives of isoxazolo[4,5-d]pyrimidine. Eur J Med Chem 43:2498–2504PubMedGoogle Scholar
  167. Wagner E, Becan L, Nowakowska E (2004) Synthesis and pharmacological assessment of derivatives of isoxazolo[4,5-d]pyrimidine. Bioorg Med Chem 12:265–272PubMedGoogle Scholar
  168. Wang K, Xiang D, Liu J, Pan W, Dong D (2008) Substituted 1H -pyrazoles and isoxazoles from cyclopropyl oximes. Synfacts 2008:0695–0695Google Scholar
  169. Watterson SH, Guo J, Spergel SH, Langevine CM, Moquin RV, Shen DR, Yarde M, Cvijic ME, Banas D, Liu R, Suchard SJ, Gillooly K, Taylor T, Rex-Rabe S, Shuster DJ, McIntyre KW, Cornelius G, D’Arienzo C, Marino A, Balimane P, Warrack B, Salter-Cid L, McKinnon M, Barrish JC, Carter PH, Pitts WJ, Xie J, Dyckman AJ (2016) Potent and selective agonists of sphingosine 1-phosphate 1 (S1P1): Discovery and SAR of a novel isoxazole based series. J Med Chem 59:2820–2840PubMedGoogle Scholar
  170. Weidner-Wells MA, Werblood HM, Goldschmidt R, Bush K, Foleno BD, Hilliard JJ, Melton J, Wira E, Macielag MJ (2004) The synthesis and antimicrobial evaluation of a new series of isoxazolinyl oxazolidinones. Bioorg Med Chem Lett 14:3069–3072PubMedGoogle Scholar
  171. Willy B, Rominger F, Müller T (2008) Novel microwave-assisted one-pot synthesis of isoxazoles by a three-component coupling-cycloaddition sequence. Synthesis 2008:293–303Google Scholar
  172. Xu Y, Wang N-Y, Song X-J, Lei Q, Ye T-H, You X-Y, Zuo W-Q, Xia Y, Zhang L-D, Yu L-T (2015) Discovery of novel N-(5-(tert-butyl)isoxazol-3-yl)-N′-phenylurea analogs as potent FLT3 inhibitors and evaluation of their activity against acute myeloid leukemia in vitro and in vivo. Bioorg Med Chem 23:4333–4343PubMedGoogle Scholar
  173. Yamamoto T, Fujita K, Asari S, Chiba A, Kataba Y, Ohsumi K, Ohmuta N, Iida Y, Ijichi C, Iwayama S, Fukuchi N, Shoji M (2007) Synthesis and evaluation of isoxazole derivatives as lysophosphatidic acid (LPA) antagonists. Bioorg Med Chem Lett 17:3736–3740PubMedGoogle Scholar
  174. Yamuna E, Kumar RA, Zeller M, Rajendra Prasad KJ (2012) Synthesis, antimicrobial, antimycobacterial and structure-activity relationship of substituted pyrazolo-, isoxazolo-, pyrimido- and mercaptopyrimidocyclohepta[b]indoles. Eur J Med Chem 47:228–238PubMedGoogle Scholar
  175. Yang H, Xu G, Pei Y (2017) Synthesis, preliminary structure-activity relationships and biological evaluation of pyridinyl-4,5-2H-isoxazole derivatives as potent antitumor agents. Chem Res Chin Univ 33:61–69Google Scholar
  176. Ye N, Zhu Y, Chen H, Liu Z, Mei FC, Wild C, Chen H, Cheng X, Zhou J (2015) Structure-activity relationship studies of substituted 2-(isoxazol-3-yl)-2-oxo-N’-phenyl-acetohydrazonoyl cyanide analogues: identification of potent exchange proteins directly activated by cAMP (EPAC) antagonists. J Med Chem 58:6033–6047PubMedPubMedCentralGoogle Scholar
  177. Yu GJ, Iwamoto S, Robins LI, Fettinger JC, Sparks TC, Lorsbach BA, Kurth MJ (2009) 3-(Arylthiomethyl)isoxazole-4,5-dicarboxamides: chemoselective nucleophilic chemistry and insecticidal activity. J Agric Food Chem 57:7422–7426PubMedPubMedCentralGoogle Scholar
  178. Yu L-F, Tückmantel W, Eaton JB, Caldarone B, Fedolak A, Hanania T, Brunner D, Lukas RJ, Kozikowski AP (2012) Identification of novel α4β2-nicotinic acetylcholine receptor (nAChR) agonists based on an isoxazole ether scaffold that demonstrate antidepressant-like activity. J Med Chem 55:812–823PubMedPubMedCentralGoogle Scholar
  179. Zhang C, Wang X, Liu H, Zhang M, Geng M, Sun L, Shen A, Zhang A (2017) Design, synthesis and pharmacological evaluation of 4,5-diarylisoxazols bearing amino acid residues within the 3-amido motif as potent heat shock protein 90 (Hsp90) inhibitors. Eur J Med Chem 125:315–326PubMedGoogle Scholar
  180. Zhang HK, Eaton JB, Fedolak A, Gunosewoyo H, Onajole OK, Brunner D, Lukas RJ, Yu LF, Kozikowski AP (2016) Synthesis and biological evaluation of novel hybrids of highly potent and selective α4β2-Nicotinic acetylcholine receptor (nAChR) partial agonists. Eur J Med Chem 124:689–697PubMedPubMedCentralGoogle Scholar
  181. Zhao N, Zuo L, Li W, Guo W, Liu W, Wang J (2017a) Greenhouse and field evaluation of isoxaflutole for weed control in maize in China. Sci Rep 7:12690–12698PubMedPubMedCentralGoogle Scholar
  182. Zhao S, Zhang X, Wei P, Su X, Zhao L, Wu M, Hao C, Liu C, Zhao D, Cheng M (2017b) Design, synthesis and evaluation of aromatic heterocyclic derivatives as potent antifungal agents. Eur J Med Chem 137:96–107PubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Institute of Pharmaceutical ResearchGLA UniversityMathuraIndia

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