OXAZOLE – ISOXAZOLE: MOLECULE OF DIVERSE BIOLOGICAL ACTIVITIES

About Authors:
*C.P.Meher, S.P.Sethy, S. M Ahmed
Department of pharmaceutical Chemistry, Maheshwara college of Pharmacy,
chitkul (V), Isnapur “X” Road, patancheru, Hyderabad.
*chaitanyameher84@gmail.com

ABSTRACT:-
Heterocyclic chemistry is vastly expanding because of the enormous amount of research work being done in this area. Heterocyclic compound are very widely distributed in nature and are particularly important because of the wide variety of physiological activities associated with this class of substances . A great deal of research is carried out to prepare new heterocyclic molecules having therapeutic uses.[1] and also so many heterocyclic derivative are synthesized till now having desired pharmacological effect. Out of them oxazole & isoxazole derivatives are catagorised in a higher position as the other heterocyclic compound possess in the hetero-chemistry. The present review is concern with the comparative study of the derivative of oxazole & isoxazole derivatives along with their pharmacological effects.

Reference Id: PHARMATUTOR-ART-1504

INTRODUCTION:-
Medicinal chemistry concerns with the discovery, development, interpretation and the identification of mechanism of action of biologically active compounds at the molecular level. An important aspect of medicinal chemistry has been to establish a relationship between chemical structure and pharmacological activity. Several of the important compound contain heterocyclic rings, e.g. heterocyclic ring are present in most of the member of vitamin B-complex , most of the alkaloids, antibiotics, chlorophyll, haemoglobin ,other plant pigment, aminoacids ,dyes, drugs, enzymes, the genetic material, DNA etc..Oxazoleis the parent compound for a vast class of heterocyclicaromaticorganic compounds. These are azoleswith an oxygen and a nitrogen separated by one carbon. Oxazoles are aromatic compoundsbut less so than the thiazoles. Oxazole is a weak base; its conjugate acidhas a pKaof 0.8, compared to 7 for imidazole. Isoxazole is an azolewith an oxygen atom next to the nitrogen. Isoxazole rings are found in some natural products, such as ibotenic acid. Isoxazoles also form the basis for a number of drugs, including the COX-2 inhibitor valdecoxib(Bextra).some of the physical as well as the chemical properties of the oxazole & isoxazole nucleus are described in table.1.

Table-1

Various physical & chemical properties of oxazole & isoxazole are similar (table-1) but substitution on different position on the nucleus of oxazole & isoxazole gives different derivative with different pharmacological effects.Oxazole does not occur in nature & thus does not play any part any part in fundamental metabolism as do imidazole & thiazole.Still most of the oxazole derivative are under clinical trial or under investigation for treatment of disease like cancer , diabetic. some derivative of oxazole derivative are used as plateletaggregation inhibitor, calcium imaging, NSAID, wavelength shifter, treatment of absence seizure , antibiotic activity. Similarly the isoxazole derivative possess antibiotic activity, treatment of T.B.,U.T.I ,treatment of cancer, anti-viral ,N.S.A.I.D.,Treatment of severe rheumatoid arthritisand psoriatic arthritis.etc.

Given below is a brief account of various alterations conducted on oxazole & isoxazole ring containing few importent marketed drug,dugs under clinical trial and their associated biological activities in table-2 & table-3 respectively.

Oxazole

Table-2

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ISOXAZOLE

Table-3

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CONCLUSION:-
The chemistry of heterocyclic compound is logical as that of aliphatic or aromatic compounds.their study is of great interest both from the theoretical as well as practical stand point.heterocyclic compounds occur widely in nature and in a variety of non-naturally occuring compound.a large number of heterocyclic compound are essential to life.The reviewed oxazole & isoxazole moiety has shown a wide spectrum of biological activities. The various substituted oxazole & isoxazole are having significant antibacterial activity. Significant analgesic, anti-inflammatory, anti tumor activity, antidiabetic, anti depressant, antiviral activity.The oxazole & isoxazole nucleus based pharmaceutical are rapidly becoming very important class of therapeutic agents and are likely to replace many existingorganic based pharmaceuticals in the very near future. The oxazole & isoxazole based pharmaceuticals will be produced on a large scale by modern drug discovery company by different research development processes and will become available commercially for therapeutic use. With the key benefits including favorable time to market and high rate of success in clinical trial compared with traditional pharmaceuticals due to diverse biological action with less toxicity, so in future therapeutic oxazole & isoxazole drug will play a vital role in the treatment of different diseases. The biological profiles of this new generation of oxazole & isoxazole represent much progress with regard to the older compounds.

REFERENCES:-
[1] ORGANIC CHEMISTRY, Reactions & reagents, O.P.Agrawal. page-628.
[2] "Phase III program of Aleglitazar started". Roche., "Statement on a nonproprietary name adopted by the USAN Council: Aleglitazar". United States Adopted Names. American Medical Association.
[3] Hulin, Bernard; Clark, David A.; Goldstein, Steven W.; McDermott, Ruth E.; Dambek, Paul J.; Kappeler, Werner H.; Lamphere, Charles H.; Lewis, Diana M. et al. (1992). "Novel thiazolidine-2,4-diones as potent euglycemic agents". Journal of Medicinal Chemistry 35 (10): 1853–64
[4] The Merck Index, 12th Edition. 3432.
[5] Pankuch, Glenn A.; Kelly, Linda M.; Lin, Gengrong; Bryskier, Andre; Couturier, Catherine; Jacobs, Michael R.; Appelbaum, Peter C. (2003). "Activities of a new oral streptogramin, XRP 2868, compared to those of other agents against Streptococcus pneumoniae and Haemophilus species". Antimicrobial Agents and Chemotherapy 47 (10): 3270–3274.
[6] Rynkiewicz, G., Poenie, M., and Tsien, R.Y. (1985). "A new generation of Ca2+ indicators with greatly improved fluorescence properties*". J. Biol. Chem. 260 (6): 3440–3450.
[7] Mitscher, Lester A.; Lednicer, Daniel (1977). The organic chemistry of drug synthesis. New York: Wiley.
[8] Gribble, G. W. In Oxazoles: Synthesis, Reactions, and Spectroscopy, A; Palmer, D. C., Ed.; Wiley: New York, 2003; Vol. 60.
[9] Nissen SE, Wolski K, Topol EJ (November 2005). "Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus". JAMA 294 (20): 2581–6.
[10] Greenblatt DJ, Matlis R, Scavone JM, Blyden GT, Harmatz JS, Shader RI (March 1985). "Oxaprozin pharmacokinetics in the elderly". British Journal of Clinical Pharmacology 19 (3): 373–8.
[11] Mechanism of Liquid Scintillation Counting, National Diagnostics, retrieved 24 Sept 2007.
[12] Preud'homme, Jean; Tarridec, Paul; Belloc, Andre (1968). "Isolation, characterization, and identification of the components of pristinamycin". Bulletin de la Societe Chimique de France (2): 585–591.
[13] Borthwick AD, Liddle J (July 2011). "The Design of Orally Bioavailable 2,5-Diketopiperazine Oxytocin Antagonists: From Concept to Clinical Candidate for Premature Labour". Medicinal Research Reviews 31 (4): 576–604.
[14] Tsuro, T., et al. (1986). "Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine resistant sublines". Cancer Res. 46 (1): 381–385
[15] lbrecht S, Hering W, Ihmsen H, Schwilden H, Schüttler J. Pharmacokinetic-pharmacodynamic modeling in phase II of drug development. A comparative study with young and old volunteers with benzdiazepine as an example. (German) Anasthesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie. 1999 Oct;34(10):634-7.
[16] Mukhtar, T. A.; Wright, G.D. (2005). "Streptogramins, Oxazolidinones, and Other Inhibitors of Bacterial Protein Synthesis". Chem. Rev 105 (2): 529–542.
[17] Heterocyclic chemistry, Raj.k.bansal, 4th edition page-478,479
[18] Hin-ya, Kazuo; Wierzba, Konstanty; Matsuo, Ken-ichi; Ohtani, Toshio; Yamada, Yuji; Furihata, Kazuo; Hayakawa, Yoichi; Seto, Haruo (2001). "Telomestatin, a novel telomerase inhibitor from Streptomyces anulatus". Journal of the American Chemical Society 123 (6): 1262–1263.
[19] Pharmaceutical organic chemistry,G.R Chatwal,page-2.13
[20] Arneric SP, Sullivan JP, Briggs CA, Donnelly-Roberts D, Anderson DJ, Raszkiewicz JL, Hughes ML, Cadman ED, Adams P, Garvey DS' (July 1994). "(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: I. In vitro characterization". J. Pharmacol. Exp. Ther. 270 (1): 310–8.
[21] Purves, Dale, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and Leonard E. White (2008). Neuroscience. 4th ed.. Sinauer Associates. pp. 128–33
[22] Bisoxazoline (BOX) Ligand-Metal Complexes: An Emerging Chiral Catalyst Ramkrishna Basak Synlett 2003, No. 8, 1223–1224.
[23] Nava S, Crotti P, Gurrieri G, Fracchia C, Rampulla C (January 1992). "Effect of a beta 2-agonist (broxaterol) on respiratory muscle strength and endurance in patients with COPD with irreversible airway obstruction". Chest 101 (1): 133–40.
[24] David Greenwood .et.al(2008). Antimicrobial drugs: chronicle of a twentieth century medical triumph. Oxford University Press US. pp. 124.
[25] Miranda-Novales G, Leaños-Miranda BE, Vilchis-Pérez M, Solórzano-Santos F (2006). "In vitro activity effects of combinations of cephalothin, dicloxacillin, imipenem, vancomycin and amikacin against methicillin-resistant Staphylococcus spp. strains". Ann. Clin. Microbiol. Antimicrob. 5: 25.
[26] Badio, B.; Garraffo, H. M.; Plummer, C. V.; Padgett, W. L.; Daly, J. W. (1997). "Synthesis and nicotinic activity of epiboxidine: an isoxazole analogue of epibatidine". European Journal of Pharmacology 321 (2): 189–194.
[27] Sutherland R, Croydon EA, Rolinson GN (November 1970). "Flucloxacillin, a new isoxazolyl penicillin, compared with oxacillin, cloxacillin, and dicloxacillin". Br Med J 4 (5733): 455–60.
[28] Schönbächler, R. D. (1999). "Evaluation of Three Cocaine Analogues as PET tracers for the Dopamine Transporter and Synthetic Approaches to [F-18]-DFMO" (pdf). Diss. Naturwiss. ETH Zürich 13287.
[29] Haupt E, Köberich W, Beyer J, Schöffling K (December 1971). "Pharmacodynamic aspects of tolbutamide, glibenclamide, glibornuride and glisoxepide. I. Dose response relations and repeated administration in diabetic subjects". Diabetologia 7 (6): 449–54.
[30] Becker, A; Grecksch, G; Bernstein, HG; Höllt, V; Bogerts, B (1999). "Social behaviour in rats lesioned with ibotenic acid in the hippocampus: quantitative and qualitative analysis". Psychopharmacology 144 (4): 333–8.
[31] Fagervall I, Ross SB (April 1986). "Inhibition of monoamine oxidase in monoaminergic neurones in the rat brain by irreversible inhibitors". Biochemical pharmacology 35 (8): 1381–
[32] Pinto P, Dougados M (2006). "Leflunomide in clinical practice". Acta reumatológica portuguesa 31 (3): 215–24
[33] Carroll, F.; Pawlush, N.; Kuhar, M.; Pollard, G.; Howard, J. (2004). "Synthesis, monoamine transporter binding properties, and behavioral pharmacology of a series of 3beta-(substituted phenyl)-2beta-(3'-substituted isoxazol-5-yl)tropanes". Journal of Medicinal Chemistry 47 (2): 296–302.
[34] Brough, Paul A.; Aherne, Wynne; Barril, Xavier; Borgognoni, Jenifer; Boxall, Kathy; Cansfield, Julie E.; Cheung, Kwai-Ming J.; Collins, Ian et al. (2008). "4,5-Diarylisoxazole Hsp90 Chaperone Inhibitors: Potential Therapeutic Agents for the Treatment of Cancer". Journal of Medicinal Chemistry 51 (2): 196–218.
[35] Health Canada Endorsed Important Safety Information on Valdecoxib Tablets, A Selective Cyclo-oxygenase-2 (COX-2) Inhibitor Non-Steroidal Anti-Inflammatory Drug (NSAID), April 21, 2005
[36] Pevear D, Tull T, Seipel M, Groarke J (1999). "Activity of pleconaril against enteroviruses". Antimicrob Agents Chemother 43 (9): 2109–15
[37] Barron, S.; Mclaughlin, J.; See, J.; Richards, V.; Rosenberg, R. (2009). "An allosteric modulator of alpha7 nicotinic receptors, N-(5-Chloro-2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea (PNU-120596), causes conformational changes in the extracellular ligand binding domain similar to those caused by acetylcholine". Molecular Pharmacology 76 (2): 253–263.
[38] Wookey, A.; Turner, P. J.; Greenhalgh, J. M.; Eastwood, M.; Clarke, J.; Sefton, C. (2004). "AZD2563, a novel oxazolidinone: definition of antibacterial spectrum, assessment of bactericidal potential and the impact of miscellaneous factors on activity in vitro". Clinical Microbiology and Infection 10 (3): 247–254
[39] Chao, Qi; Sprankle, Kelly G.; Grotzfeld, Robert M.; Lai, Andiliy G.; Carter, Todd A.; Velasco, Anne Marie; Gunawardane, Ruwanthi N.; Cramer, Merryl D.; Gardner, Michael F.; James, Joyce; Zarrinkar, Patrick P.; Patel, Hitesh K.; Bhagwat, Shripad S. (2009). "Identification of N-(5-tert-Butyl-isoxazol-3-yl)-N'-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3]benzothiazol-2-yl]phenyl}urea Dihydrochloride (AC220), a Uniquely Potent, Selective, and Efficacious FMS-Like Tyrosine Kinase-3 (FLT3) Inhibitor". Journal of Medicinal Chemistry 52 (23): 7808–7816.
[40] Lindsey, K.P., Wilcox, K.M., Votaw, J.R., Goodman, M.M., Plisson, C., Carroll, F.I., Rice, K.C., Howell, L.L. Effects of dopamine transporter inhibitors on cocaine self-administration in rhesus monkeys: relationship to transporter occupancy determined by positron emission tomography neuroimaging. Journal of Pharmacology and Experimental Therapeutics, 309: 959-969, 2004.
[41] Runyon, S. P.; Carroll (2006). "Dopamine transporter ligands: recent developments and therapeutic potential". Current Topics in Medicinal Chemistry 6 (17): 1825–1843
[42] Barst RJ, Langleben D, Frost A et al. (2004). "Sitaxsentan therapy for pulmonary arterial hypertension". American Journal of Respiratory Critical Care Medicine 169 (4): 441–447.
[43] Aveo Kidney Cancer Drug Shows Success; Shares Up, By John Kell, Dow Jones Newswires
[44] "Pfizer to pay $2.3 billion to resolve criminal and civil health care liability relating to fraudulent marketing and the payment of kickbacks". Stop Medicare Fraud, US Dept of Health & Human Svc, and of Justice. stopmedicarefraud.gov/pfizerfactsheet.html. Retrieved 2012-07-04.
[45] Sternfeld, F; Carling, RW; Jelley, RA; Ladduwahetty, T; Merchant, KJ; Moore, KW; Reeve, AJ; Street, LJ et al. (2004). "Selective, orally active gamma-aminobutyric acidA alpha5 receptor inverse agonists as cognition enhancers". Journal of Medical Chemistry 47 (9): 2176–9.