Synthesis of Antipyrine drug and its derivatives.pptx

Synthesis of Antipyrine Derivatives
Antipyrine is an drug which is used to reduce pain and inflammation.
Antipyrine consist of pyralozolone skeleton

1. 1 Synthesis of Antipyrine Derivatives

2. Antipyrine Structure Properties Synthesis of Antipyrine hydrazone derivatives Reaction Mechanism Synthesis of Antipyrine pyrazole derivatives Reaction Mechanism Characterization Biological activity Conclusion 2 Content

3. 3 Scheme Biological activity IIIa does not give reaction Step 1: Synthesis of Antipyrine hydrazone derivatives Step 2: Synthesis of pyrazole Antipyrine derivatives 1. Shchegol . K, E. V., Khudina , O. G., Anikina , L. V., Burgart , Y. V., and Saloutin , V. I. Synthesis, analgesic and antipyretic activity of 2-(antipyrin-4-yl) hydrazones of 1, 2, 3-triketones and their derivatives.  Pharmaceutical Chemistry Journal ,  40 (1): 373-376 (2006).

4. Antipyrine 4 Analgesic Anti-inflammatory Antiviral Antipyrine Antipyrine is an drug which is used to reduce pain and inflammation. Antipyrine consist of pyralozolone skeleton A ntioxidant Antibacterial Antipyretic Structure

5. Antipyrine Name Anti means against and pyrine derived from pyretic Other name Phenazone Analgesine 1 Today Uses Antipyrine-Benzocaine Otic used in middle ear infections 3 History In 1883 L. Knorr synthesized Antipyrine in search for a synthetic method for quinine First medically and commercially successful antipyretic medicine 2 5

6. Reason to synthesize Antipyrine derivative 1 2 To enhance the antipyrine properties by modifying it To obtain new antipyretic medicine other than traditional medicine 3 To obtain new low toxic medicine 6

7. Synthesis of Antipyrine hydrazones derivative 1,3-diketones ( Ia and Ib ) react with Antipyrine 4 diazonium chloride (II) in the presence of sodium acetate. Reaction 7

8. Mechanism 8 It is an azo coupling reaction Step 1: Tautomerization of 1,3 diketone Step 2: Attack of enol as nucleophile Step 3: Tautomerization of product

9. Synthesis of 3-tetrafluoroethyl pyrazole derivatives IIIb enters into cyclocondensation with alkyl hydrazine (di-nucleophile) to yield 3-tetrafluoroethyl pyrazole derivatives of Antipyrine (IV, V). 9 IIIa does not give reaction

10. Mechanism 10 = R

11. 11 Characterization

12. Characterization IR spectroscopy 1 1 H NMR 2 12

13. 13 IR spectrum (cm – 1 ): 3470 (NH) 1670, 1725 (C=O) 1620 (C=N) 1530 (C=C) 1490 (C=C) phenyl (CN) 1800 (C=O) acid halide 1100 – 1340 (C–F) Phenyl proton N-H Phenyl proton N-CH 3 2(methyl protons) CH 3 Antipyrine hydrazone derivative change change

14. 14 IR spectrum (cm – 1 ): 1545 (N=N) 1530 (C=C) 1620 (C=N) 1000 to 1250 (CN) 1300-1000 (O-C) 3300-3600 (O-H) CH 3 of antipyrine N-CH 2 CH 2 -OH -H Phenyl protons Antipyrine pyrazole derivative Phenyl proton CH 3 N-CH 3

15. 15 Biological activity

16. 16 Antipyretic activity toxicity Analgesic activity Biological activity Antipyrine derivative Biological activity

17. Biological activity 17

18. 18 Antipyretic activity

19. Antipyretic activity 19 Pyrogenal injection (intravenous) that induce fever Control group 180 – 240 g (6 rats) Temp increases 1. Shchegol . K, E. V., Khudina , O. G., Anikina , L. V., Burgart , Y. V., and Saloutin , V. I. Synthesis, analgesic and antipyretic activity of 2-(antipyrin-4-yl) hydrazones of 1, 2, 3-triketones and their derivatives.  Pharmaceutical Chemistry Journal ,  40 (1): 373-376 (2006).

20. Test groups Antipyretic activity 20 180 – 240 g Compound Pyrogenal injection Compound is taken orally After 2hrs Temp measured at different interval from rectum

21. 21 Antipyretic activity of synthesized compound III a= III b = IV = V =

22. 22 Toxicity It is the degree to which a chemical substance or a particular mixture of substances can damage an organism.  III a= III b = IV = V = Other application

23. Conclusion 23

24. Conclusion Antipyrine derivatives synthesized and characterized by IR, 1 H NMR spectroscopy. 3-tetrafluoroethyl pyrazole derivative contain hydroxy group has show better antipyretic activity than any synthesized compound. 1 3 It was concluded that hydrazone Antipyrine derivative contain methyl substitute are considered more toxic than others 2 24

25. References Shchegol’kov , E. V., Khudina , O. G., Anikina , L. V., Burgart , Y. V., and Saloutin , V. I. Synthesis, analgesic and antipyretic activity of 2-(antipyrin-4-yl) hydrazones of 1, 2, 3-triketones and their derivatives.  Pharmaceutical Chemistry Journal ,  40 (1): 373-376 (2006). Fadda, A. A., and Elattar , K. M. Design and synthesis of some enaminonitrile derivatives of antipyrine as potential novel anti-inflammatory and analgesic agents. Journal of Biosciences and Medicines 3 (11): 114 (2015). Sahoo, J., Sahoo, C. R., Sarangi, P. K. N., Prusty , S. K., Padhy , R. N., and Paidesetty , S. K. Molecules with versatile biological activities bearing antipyrinyl nucleus as pharmacophore.  European Journal of Medicinal Chemistry ,  186 (1): 111911 (2020). Urbaniak , W., Jurek , K., Witt, K., Goraczko , A., Staniszewski , B., and Mickiewicz, A. Properties and application of diketones and their derivatives.  Chemik ,  65 (4): 273-278 (2011). Lupu , G., Bel , L. and Andrei, S. Pain Management and antipyretic Used in Small Mammals during Post-Operative Period with an Emphasis on Metamizole (Dipyrone) as an Alternative Medication.  Molecules ,  27 (21): 7434 (2022). 25

26. 26 Thank you