6.1 – Need for the study:
Oxazole is a heterocyclic organic compound that has a five-member ring, and its derivatives are used as building block for biochemicals and pharmaceutical as well as in other industrial applications such as pesticides, dyes, fluorescent brightening agents, textile auxiliaries and plastics.
It has been reported that Oxazole derivatives shows anti-inflammatory, Antibacterial, Antidiabetic, Antimycobacterial, Thrombaxine A2 and prostaglandinH2 receptor antagonist activities.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed categories of drugs worldwide in the treatment of pain and inflammation in many conditions.
NSAIDs are used primarily to treat inflammation, mild to moderate pain, and fever. Specific uses include the treatment of headaches, arthritis, sports injuries, and menstrual cramps. Aspirin is used to inhibit the clotting of blood and prevent strokes and heart attacks in individuals at high risk. NSAIDs also are included in many cold and allergy preparations. Two drugs in this category, ibuprofen and naproxen, also reduces fever.
6.2 – Review of the literature
1. M.J.Aaglwae, et.al have synthesized some Antibacterial oxazolone derivatives by condensation of aroyloxy-aminoaceticacid with aldehyde in presence of ethanol, acetic acid and sodium citrate.
2. Louis Rosenfeld, et.al have synthesized Ifetrobansodium[oxaxole derivative] an effective thrombaxine A2 and prostaglandin H2-receptor antagonist, Which effects on Myocardialischaemia, hypertension, stroke, etc.,
3. Vadim A, et.al have synthesized Novel-[(biphenyl)propyl]-isoxazole derivative for inhibition of human rhinovirus-2 and cox sockievirus B3 replication.
4. A.Herrera, et.al have synthesized 2-Substituted-5-methyl-4-methylthio-1,3-oxazoles in a good yield from reaction of 1-(methylthio)-acetone with different nitriles in presence of trifilicanhydride.
5. Song.Y, et.al have studied on synthesis, SAR, and in vivo evaluations of thiazolone and oxazolone derivatives as a novel class of potent, selective and orally active COX-2 inhibitors.
6. Hiroshi Imoto, et.alstudy on Non- thiazolidinedione Anti diabetic agent, preparation and biological activities of TAK559[-4-{4-[(5methyl-2-phenyl-1-3oxazole-4-yl)-methoxy]benzyloximino}-4 phenyl butyric acid.
7. Jongchanlee, et.al have studied on novel direct synthesis of multi substituted oxazoles from ketones.[2,5- and 2,4,5]sub oxazoles due to their existence in sub structures for many pharmaceuticals.
8. Sasaki H, et.al have studied the synthesis and thrombaxine A2 and prostaglandin-H2 receptor antagonist activity of a novel series of optically active 6-Nitro-2,3-dihydroimidazo[2,1-b]oxazoles that would be effective against both drug-susceptible and drug-resistant strains of Mycobacterium Tuberculosis.
9. Puig C, et.al have studied the synthesis and biological evaluation of 3,4-diaryloxazolones: A new class of orally active COX-2 inhibitos with superior in vivo Antiinflammatory properties.
10. Biplap De, et.al have synthesized some oxazolinones and imidazolinones and screened for their antimicrobial activity.
6.3 – Objective of the Study:
The above quoted data indicates that Oxazole nucleus is a perspective molecule for further investigations. The present study is an attempt to open up novel possibilities of preparation of some Oxazole derivatives exhibiting anti-inflammatory activity.
The work consists of
a)Synthesis of some new Oxazole derivatives.
b)Study of the structures by IR and 1H NMR & Mass spectrum.
c)Investigation of possible anti-inflammatory activity.
In the present scheme, Dibromoacetyl anthranilic acid is prepared from anthranilic acid. This is treated with 2% NaOH and various aromatic aldehydes to get Dibromo-2-[3-aryl-acryl amino] benzoic acid. This on further cylisation with hydroxyl amine hydrochloride give Dibromo-1,2 oxazole amino benzoic acid. Mannich reaction of above compounds gives Dibromo-aryl-1,2 oxazole amino benzoic acid compounds.
7.0 / Materials and Methods:
7.1 Source of Data:
Chemical abstracts & other journals like Journal of Medicinal Chemistry,Journal ofAntimicrobial Chemotherapy, EuropeanJournal Medicinal Chemistry, journal of heterocyclic Chemistry,Indian journal of Heterocyclic chemistry, journal of pharmaceutical sciencesand e-journals.
7.2 - Method of collection of data:
Chemicals & other reagents will be collected from standard companies. The reactions will be monitored by thin layer chromatography. The products will be purified as per standard protocols. Structure of the synthesized molecules will be confirmed by spectral data.
7.3 - Does the study require any investigations or interventions to be conducted on
patients or other humans or animals? If so, Please describe briefly.
Yes, the study requires investigation on albino rats.
7.4 – Has ethical clearance been obtained from your Institution in case of 7.3?
No. The protocol is being submitted to IAEC.
8.0 / List of References:
1. M. J. Aaglwae, S. S. Dhule, S. S. Bahekar, P. S. Wakte and D. B. Shinde. Synthesis and Antibacterial Activity of Some Oxazolone Derivatives. Journal of the Korean Chemical Society2003; 47,2: 33-136.
2. Louis Rosenfeld, Gary J. Grover and Charles T. Stier, Jr: Ifetroban Sodium: An Effective TxA2/PGH2 Receptor Antagonist. Cardiovascular Drugs reviews,2001; 19, 2: 97–115.
3. Vadim A. Makarov, Olga B. Riabova, Vladimir G. Granik, Peter Wutzler and Michaela Schmidtke, Novel [(biphenyloxy)propyl]isoxazolederivatives for inhibition of humanrhinovirus 2 and coxsackievirus B3 replication. Journal of Antimicrobial Chemotherapy 2005;55(40): 483-488.
4. A. Herrera, R. Martinez-Alvarez, P. Ramiro, D. Molero and J. Almy synthesis of 2substituted 5-methyl,4methylthio-1,3-oxazoles in a good yield from reaction of 1-(methylthio)acetone with different nitriles in presence of trifilicanhydride. J. Org. Chem., 2006, 71: 3026-3032.5. Song Y, Connor DT, Doubleday R, Sorenson RJ, Sercel AD, Unangst PC, Roth BD, Gilbertsen RB, Chan K, Schrier DJ, Guglietta A, Bornemeier DA and Dyer RD: Synthesis, structure-activity relationships and in vivo evaluations of substituted di-tert-butylphenol as a novel class of potent, selective, and orally active cyclooxygenase-2 inhibitors. 1, Thiazolone and oxazoloneseries. J Med Chem 1999,42(7): 1151-60.
6. Hiroshi Imoto, Mitsharu Matsumato, Hiroyuki Okada, junichi Sakamato, Hiroyuki Kimura, masami Nonaka,Yutaka Kiyota and Momose. study on Non-thiazolidinedione Antidiabetic agent, preparation and biological activities of TAK559[-4-{4-[(5methyl-2-phenyl-1-3oxazole-4-yl)methoxy]benzyloximino}-4phenylbutyric acid. Chem, pharm, bull., 2001; 52(1): 120-124.
7. Jongchanlee and Yong chanlee. Novel direct synthesis of multi substituted oxazoles from ketones. [2,5- and 2,4,5] sub oxazoles due to their existence in sub structures for many pharmaceuticals.Bull. Korean Chem. Soc.2006 ;24, 7:893.
8. Sasaki H, Haraguchi Y, Itotani M, Kuroda H, Hashizume H, Tomishige T, Kawasaki M, Matsumoto MKomatsu M, and Tsubouchi H. Synthesis and antituberculosis activity of a novel series of optically active 6-Nitro-2,3-dihydroimidazo[2,1-b]oxazoles. J Med Chem.2006, 49(26), 7854-60.
9. Puig C, Crespo MI, Godessart N, Feixas J, Ibarzo J, Jiménez JM, Soca L, Cardelús I, Heredia A, Miralpeix M, Puig J, Beleta J, Huerta JM, López M, Segarra V, Ryder H and Palacios JM. Synthesis and biological evaluation of 3,4-diaryloxazolones: A new class of orally active cyclooxygenase-2-inhibitors. : J Med Chem.2000;.43(2): 214-23.
10.Biplab De, Jayanta Kumar Gupta and Venkatapuram Sampath Saravanan. Synthesis of some oxazolinones and imidazolinones and screening for their antimicrobial activity. Acta Pharm. 2005;55 (3): 287-96.