The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

Isoxazoles     1,2-oxazole

Synonyms: ISOXAZOLE, Isooxazole, PubChem8623, SureCN1318, CHEMBL13257, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of isoxazole

  • Microcin B17 (MccB17) is a 3.1-kDa Escherichia coli antibiotic that contains thiazole and oxazole heterocycles in a peptide backbone [1].
  • Recently, we reported on a series of isoxazoline and isoxazole monobasic noncovalent inhibitors of factor Xa which show good potency in animal models of thrombosis [2].
  • The biosynthetic gene cluster of goadsporin, a polypeptide antibiotic containing thiazole and oxazole rings, was cloned from Streptomyces sp. TP-A0584 [3].
  • In vitro metabolism studies on the isoxazole ring scission in the anti-inflammatory agent lefluonomide to its active alpha-cyanoenol metabolite A771726: mechanistic similarities with the cytochrome P450-catalyzed dehydration of aldoximes [4].
  • Accordingly, the 2,3-dimethyl-5-(4-methylsulfonylphenyl)-4-phenyl-4-isoxazoline (3), which possesses an electron rich central 5-membered isoxazole ring, could serve as a lead compound to develop novel drugs to treat prostate cancer [5].

Psychiatry related information on isoxazole

  • The agonistic behavior of furanfurin against A1 receptors is preserved only when the furan ring is substituted with isosteric pentatomic ring systems such as oxazole, thiazole or thiophene, and the carboxamide group is unsubstituted [6].

High impact information on isoxazole

  • From this, we discovered that CAC-1098 (aurintricarboxylic acid) and CBI-0997 (5-(2,4-dimethoxy-5-ethylphenyl)-4-(4-bromophenyl) isoxazole) inhibited migration of MDA-MB-231 cells with IC50 = 5 and 50 nM, respectively [7].
  • We have examined the properties of LY475776, an intrinsically photoactivable MRP1-specific tricyclic isoxazole modulator that inhibits leukotriene C(4) transport by this protein in a GSH-dependent manner [8].
  • Ethidium, thiazole orange, and oxazole yellow homodimers form stable, highly fluorescent complexes with double-stranded DNA that can be detected in gels by a laser-excited, confocal, fluorescence scanning system with a sensitivity higher than that attainable with radioisotopic labeling [9].
  • The results also attribute the activity boost upon substitution of oxazole by oxadiazole to reduced steric interactions in the active site and a lower torsional energy penalty upon binding [10].
  • The synthesis was completed by cationic cyclization to form 14 diastereoselectively and subsequent introduction of the terminal oxazole subunit [11].

Chemical compound and disease context of isoxazole

  • Replacement of the pyridylmethyl moiety in indinavir with a pyridyl oxazole yielded HIV-1 protease inhibitors (PI) with greatly improved potency against PI-resistant HIV-1 strains [12].

Biological context of isoxazole

  • The tetracyclic target ring system was assembled by an internal azomethine ylide cycloaddition reaction based on silver ion-assisted intramolecular oxazole alkylation and cyanide-induced ylide generation via a labile oxazoline intermediate (62 to 66) [13].
  • The analyses of the quantitative structure--activity relationships showed that the molecular conformation and the dipole moment, as well as the hydrophobicity at the oxazole C5-site, were important for high activity [14].
  • Structure-activity relationship studies have demonstrated that electronegative substituents on the 2-phenyl portion of the oxazole tail increased the ex vivo potency of these inhibitors [15].
  • However, among these isoxazole derivatives, the cis-isomer 14b was identified as a potent inducer of apoptosis, and its activity was found to be 6.5 and 4 times superior than that of 13-cis- and 9-cis-retinoic acids, respectively [16].
  • However, the oxazole 11f, which is isomeric with 26, inhibits ADP-induced human platelet aggregation in vitro with an IC50 of 0.027 microM, 6-fold more potent than 3, 26, or 35 [17].

Anatomical context of isoxazole


Associations of isoxazole with other chemical compounds

  • Since the discovery of (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl) propionic acid (AMPA) in 1980, numerous analogs built around the isoxazole scaffold have shown remarkable selectivity for specific ionotropic glutamate receptors, but strong side effects in human clinical trials have shown the need for improvement [20].
  • Although members of the imidazole, thiazole or isoxazole classes generally have weak binding for the ER, several members of the pyrazole class show good binding affinity [21].
  • 2D NOESY NMR spectroscopy indicates the presence of both conformations about the ring juncture, at room temperature, as evidenced by correlations for both alkyl groups on the isoxazole with the C-2 methyl on the DHP moiety [22].
  • The structure-activity relationships provide insight into the topographical relationship between the diphenylated oxazole ring and the carboxylic acid terminus that comprise the nonprostanoid prostacyclin mimetic pharmacophore [23].
  • The trifluoromethyl-substituted oxazole 24 was the best compound of the oxazole series in both the ex vivo (6 h pretreated rats) and in vivo (3 h pretreated rats) RPAR assay with ED50 values of approximately 1 and 3.6 mg/kg, respectively, but was weakly active in the allergic guinea pig assay [15].

Gene context of isoxazole

  • Oxazole 30 bound to PAR-1 with an IC50 of 1.6 microM, and gave IC50 values of 25 microM and 6.6 microM against alpha-thrombin- and SFLLRN-NH2-induced platelet aggregation, respectively [24].
  • All the isoxazole derivatives were inactive on both COX isoforms [25].
  • Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP- binding cassette (ABC) drug transporters [26].
  • The isoxazole moiety of ATPO acts primarily as a spacer, and other scaffolds could potentially be used [27].
  • Oxazole 39 had excellent solubility and good oral PK when dosed as the bis-mesylate salt and demonstrated moderate in vivo efficacy against HT29 human colon tumor xenografts [28].

Analytical, diagnostic and therapeutic context of isoxazole

  • Cells undergoing apoptosis were simultaneously identified by the TdT-mediated biotin-dUTP nick-end labeling (TUNEL) method and a streptavidin-conjugated far-red fluorophore, and nuclear DNA was stained with oxazole yellow dimer (YOYO-1) [29].
  • During metabolism studies of valdecoxib by liquid chromatography/tandem mass spectrometry, we observed a novel mass spectral rearrangement involving an isoxazole ring for some of the metabolites in the negative ion mode [30].
  • We have developed a homogeneous quantitative assay of DNA/RNA by performing PCR in the presence of an oxazole yellow derivative, a fluorescent DNA intercalative dye, and monitoring the fluorescence intensity of the PCR reaction mixture during PCR cycles [31].
  • Sulfanilamide or 3-amino-5-methyl isoxazole, on the other hand, could be potential alternative therapies in HIV-seropositive patients with a history of skin reactions to SMX [32].
  • Guided by X-ray crystallography, we have extended the structure-activity relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor (1) and more potent and equally selective (>20-fold selectivity over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified [33].


  1. In vitro characterization of DNA gyrase inhibition by microcin B17 analogs with altered bisheterocyclic sites. Zamble, D.B., Miller, D.A., Heddle, J.G., Maxwell, A., Walsh, C.T., Hollfelder, F. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  2. Discovery of 1-[3-(aminomethyl)phenyl]-N-3-fluoro-2'-(methylsulfonyl)-[1,1'-biphenyl]-4-yl]-3-(trifluoromethyl)-1H-pyrazole-5-carboxamide (DPC423), a highly potent, selective, and orally bioavailable inhibitor of blood coagulation factor Xa. Pinto, D.J., Orwat, M.J., Wang, S., Fevig, J.M., Quan, M.L., Amparo, E., Cacciola, J., Rossi, K.A., Alexander, R.S., Smallwood, A.M., Luettgen, J.M., Liang, L., Aungst, B.J., Wright, M.R., Knabb, R.M., Wong, P.C., Wexler, R.R., Lam, P.Y. J. Med. Chem. (2001) [Pubmed]
  3. Cloning and characterization of the goadsporin biosynthetic gene cluster from Streptomyces sp. TP-A0584. Onaka, H., Nakaho, M., Hayashi, K., Igarashi, Y., Furumai, T. Microbiology (Reading, Engl.) (2005) [Pubmed]
  4. In vitro metabolism studies on the isoxazole ring scission in the anti-inflammatory agent lefluonomide to its active alpha-cyanoenol metabolite A771726: mechanistic similarities with the cytochrome P450-catalyzed dehydration of aldoximes. Kalgutkar, A.S., Nguyen, H.T., Vaz, A.D., Doan, A., Dalvie, D.K., McLeod, D.G., Murray, J.C. Drug Metab. Dispos. (2003) [Pubmed]
  5. Effect of cyclooxygenase-2 (COX-2) inhibitors on prostate cancer cell proliferation. Srinath, P., Rao, P.N., Knaus, E.E., Suresh, M.R. Anticancer Res. (2003) [Pubmed]
  6. C-nucleoside analogues of furanfurin as ligands to A1 adenosine receptors. Franchetti, P., Cappellacci, L., Marchetti, S., Martini, C., Costa, B., Varani, K., Borea, P.A., Grifantini, M. Bioorg. Med. Chem. (2000) [Pubmed]
  7. Blocking tumor cell migration and invasion with biphenyl isoxazole derivative KRIBB3, a synthetic molecule that inhibits Hsp27 phosphorylation. Shin, K.D., Lee, M.Y., Shin, D.S., Lee, S., Son, K.H., Koh, S., Paik, Y.K., Kwon, B.M., Han, D.C. J. Biol. Chem. (2005) [Pubmed]
  8. GSH-dependent photolabeling of multidrug resistance protein MRP1 (ABCC1) by [125I]LY475776. Evidence of a major binding site in the COOH-proximal membrane spanning domain. Mao, Q., Qiu, W., Weigl, K.E., Lander, P.A., Tabas, L.B., Shepard, R.L., Dantzig, A.H., Deeley, R.G., Cole, S.P. J. Biol. Chem. (2002) [Pubmed]
  9. Stable fluorescent dye-DNA complexes in high sensitivity detection of protein-DNA interactions. Application to heat shock transcription factor. Rye, H.S., Drees, B.L., Nelson, H.C., Glazer, A.N. J. Biol. Chem. (1993) [Pubmed]
  10. Elucidation of fatty acid amide hydrolase inhibition by potent alpha-ketoheterocycle derivatives from Monte Carlo simulations. Guimarães, C.R., Boger, D.L., Jorgensen, W.L. J. Am. Chem. Soc. (2005) [Pubmed]
  11. First enantiospecific total synthesis of the antitubercular marine natural product pseudopteroxazole. Revision of assigned stereochemistry. Davidson, J.P., Corey, E.J. J. Am. Chem. Soc. (2003) [Pubmed]
  12. The design, synthesis and evaluation of novel HIV-1 protease inhibitors with high potency against PI-resistant viral strains. Zhang, F., Chapman, K.T., Schleif, W.A., Olsen, D.B., Stahlhut, M., Rutkowski, C.A., Kuo, L.C., Jin, L., Lin, J.H., Emini, E.A., Tata, J.R. Bioorg. Med. Chem. Lett. (2003) [Pubmed]
  13. Synthetic enantiopure aziridinomitosenes: preparation, reactivity, and DNA alkylation studies. Vedejs, E., Naidu, B.N., Klapars, A., Warner, D.L., Li, V.S., Na, Y., Kohn, H. J. Am. Chem. Soc. (2003) [Pubmed]
  14. Structure-activity relationship of aldose reductase inhibitors based on X-ray crystal structures of oxazolecarbamate derivatives. Ishida, T., In, Y., Ohishi, H., Yamamoto, D., Inoue, M., Tanaka, C., Ueno, Y., Ohmomo, Y., Kanda, N., Tanaka, A. Mol. Pharmacol. (1988) [Pubmed]
  15. Azole phenoxy hydroxyureas as selective and orally active inhibitors of 5-lipoxygenase. Malamas, M.S., Carlson, R.P., Grimes, D., Howell, R., Glaser, K., Gunawan, I., Nelson, J.A., Kanzelberger, M., Shah, U., Hartman, D.A. J. Med. Chem. (1996) [Pubmed]
  16. Structure-activity relationship studies of novel heteroretinoids: induction of apoptosis in the HL-60 cell line by a novel isoxazole-containing heteroretinoid. Simoni, D., Invidiata, F.P., Rondanin, R., Grimaudo, S., Cannizzo, G., Barbusca, E., Porretto, F., D'Alessandro, N., Tolomeo, M. J. Med. Chem. (1999) [Pubmed]
  17. Nonprostanoid prostacyclin mimetics. 5. Structure-activity relationships associated with [3-[4-(4,5-diphenyl-2-oxazolyl)-5- oxazolyl]phenoxy]acetic acid. Meanwell, N.A., Romine, J.L., Rosenfeld, M.J., Martin, S.W., Trehan, A.K., Wright, J.J., Malley, M.F., Gougoutas, J.Z., Brassard, C.L., Buchanan, J.O. J. Med. Chem. (1993) [Pubmed]
  18. Distribution of multiple types of Ca2+ channels in rat sympathetic neurons in vitro. Thayer, S.A., Hirning, L.D., Miller, R.J. Mol. Pharmacol. (1987) [Pubmed]
  19. New actinomycin D analogues as superior chemotherapeutic agents against primary and advanced colon tumors and colon xenografts in nude mice. Sengupta, S.K., Kogan, Y., Kelly, C., Szabo, J. J. Med. Chem. (1988) [Pubmed]
  20. Isoxazole ionotropic glutamate neurotransmitters. Burkhart, D.J., Natale, N.R. Current medicinal chemistry. (2005) [Pubmed]
  21. Novel structural templates for estrogen-receptor ligands and prospects for combinatorial synthesis of estrogens. Fink, B.E., Mortensen, D.S., Stauffer, S.R., Aron, Z.D., Katzenellenbogen, J.A. Chem. Biol. (1999) [Pubmed]
  22. 4-Isoxazolyl-1,4-dihydropyridines: biological, theoretical, and structural studies. Natale, N.R., Triggle, D.J., Palmer, R.B., Lefler, B.J., Edwards, W.D. J. Med. Chem. (1990) [Pubmed]
  23. Nonprostanoid prostacyclin mimetics. 2. 4,5-Diphenyloxazole derivatives. Meanwell, N.A., Rosenfeld, M.J., Trehan, A.K., Wright, J.J., Brassard, C.L., Buchanan, J.O., Federici, M.E., Fleming, J.S., Gamberdella, M., Zavoico, G.B. J. Med. Chem. (1992) [Pubmed]
  24. Thrombin receptor (PAR-1) antagonists. Heterocycle-based peptidomimetics of the SFLLR agonist motif. Hoekstra, W.J., Hulshizer, B.L., McComsey, D.F., Andrade-Gordon, P., Kauffman, J.A., Addo, M.F., Oksenberg, D., Scarborough, R.M., Maryanoff, B.E. Bioorg. Med. Chem. Lett. (1998) [Pubmed]
  25. Synthesis of heteroaromatic analogues of (2-aryl-1-cyclopentenyl-1-alkylidene)-(arylmethyloxy)amine COX-2 inhibitors: effects on the inhibitory activity of the replacement of the cyclopentene central core with pyrazole, thiophene or isoxazole ring. Balsamo, A., Coletta, I., Guglielmotti, A., Landolfi, C., Mancini, F., Martinelli, A., Milanese, C., Minutolo, F., Nencetti, S., Orlandini, E., Pinza, M., Rapposelli, S., Rossello, A. European journal of medicinal chemistry. (2003) [Pubmed]
  26. Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP- binding cassette (ABC) drug transporters. Dantzig, A.H., Shepard, R.L., Pratt, S.E., Tabas, L.B., Lander, P.A., Ma, L., Paul, D.C., Williams, D.C., Peng, S.B., Slapak, C.A., Godinot, N., Perry, W.L. Biochem. Pharmacol. (2004) [Pubmed]
  27. Competitive antagonism of AMPA receptors by ligands of different classes: crystal structure of ATPO bound to the GluR2 ligand-binding core, in comparison with DNQX. Hogner, A., Greenwood, J.R., Liljefors, T., Lunn, M.L., Egebjerg, J., Larsen, I.K., Gouaux, E., Kastrup, J.S. J. Med. Chem. (2003) [Pubmed]
  28. Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors. Harris, P.A., Cheung, M., Hunter, R.N., Brown, M.L., Veal, J.M., Nolte, R.T., Wang, L., Liu, W., Crosby, R.M., Johnson, J.H., Epperly, A.H., Kumar, R., Luttrell, D.K., Stafford, J.A. J. Med. Chem. (2005) [Pubmed]
  29. Simultaneous triple fluorescence detection of mRNA localization, nuclear DNA, and apoptosis in cultured cells using confocal scanning laser microscopy. Davis, W.P., Janssen, Y.M., Mossman, B.T., Taatjes, D.J. Histochem. Cell Biol. (1997) [Pubmed]
  30. Collision-induced dissociation of valdecoxib metabolites: a novel rearrangement involving an isoxazole ring. Zhang, J.Y., Xu, F., Breau, A.P. Journal of mass spectrometry : JMS. (2004) [Pubmed]
  31. Homogeneous quantitative assay of hepatitis C virus RNA by polymerase chain reaction in the presence of a fluorescent intercalater. Ishiguro, T., Saitoh, J., Yawata, H., Yamagishi, H., Iwasaki, S., Mitoma, Y. Anal. Biochem. (1995) [Pubmed]
  32. Immune response to sulfamethoxazole in patients with AIDS. Daftarian, M.P., Filion, L.G., Cameron, W., Conway, B., Roy, R., Tropper, F., Diaz-Mitoma, F. Clin. Diagn. Lab. Immunol. (1995) [Pubmed]
  33. Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors. Zhao, H., Liu, G., Xin, Z., Serby, M.D., Pei, Z., Szczepankiewicz, B.G., Hajduk, P.J., Abad-Zapatero, C., Hutchins, C.W., Lubben, T.H., Ballaron, S.J., Haasch, D.L., Kaszubska, W., Rondinone, C.M., Trevillyan, J.M., Jirousek, M.R. Bioorg. Med. Chem. Lett. (2004) [Pubmed]
WikiGenes - Universities