atenolol

synthesis of atenolol and its impurity

1. Synthesis of atenolol and its impurity Name: manthan prabhu Synthesis of atenolol and its impurity 11/2/2017 1

2. INTRODUCTION Atenolol is a selective β 1 receptor antagonist, a drug belonging to the group of beta blockers, a class of drug primarily used in cardiovascular diseases. Introduced in 1976, Atenolol was developed as a replacement for propranolol in the treatment of hypertension. It works by slowing down the heart and reducing its workload. 11/2/2017 2

3. HISTORY Dr. James Black 1 st trade name PROPRANALOL PRONETHALOL 11/2/2017 3

4. BETA BLOCKER Beta blocker, also written β -blocker, is a class of medications that are particularly used to manage cardiac arrhythmias, and to protect the heart from a second heart attack (myocardial infarction ) after a first heart attack (i.e. secondary prevention) They are also widely used to treat hypertension. 11/2/2017 4

5. Beta blockers are competitive antagonists that block the receptor site for the endogenous Catecholamine epinephrine (adrenaline) and nor epinephrine (noradrenalin) on adrenergic Beta receptor, of the sympathetic nervous system, which mediates the fight or fight-response . ADRENALINE NORADRENALIN 11/2/2017 5

6. Three known types of beta receptor are β 1, β 2, β 3 receptor. β 1 –adrenergic receptor : are located mainly in the heart and kidney. β 2 – adrenergic receptor : are located mainly in the lungs, gastrointestinal tract , liver, uterus, vascular smooth muscles, and skeletal muscle. β 3 -adrenergic receptor : are located in fat cells. 11/2/2017 6

7. MODE OF ACTION Atenelol is a beta – adrenergic blocking agent that blocks the effects of adrenergic chemicals, for example, adrenaline or epinephrine, released by nerves of sympathetic nervous system. One of the important function of beta- adrenergic nerves is to stimulate the heart muscle to beat more rapidly. By blocking the stimulation by these nerves, atenelol reduces the heart rate and is useful in treating abnormally rapid heart rhythm. Atenelol also reduces the force of contraction of heart muscle and lowers the blood pressure. Atenelol is useful in treating angina . 11/2/2017 7

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9. MEDICINAL USES : The use of beta blocker around time of cardiac surgery decrease the risk of heart dysrhythmias(irregular heart beats). These are given during the congestive heart failure. Hypertension. Long QT syndrome. (disorder of heart electrical activity) Acute myocardial infarction. Ventricle tachycardia. [Fast heart rhythm that starts in the lower part of heart( ventricals)] Supraventricular tachycardia. 11/2/2017 9

10. 11/2/2017 10 SIDE EFFECTS : Dizziness Tiredness Drowsiness Depression Nausea Shortness of breath

11. 11/2/2017 11 Atenolol Structure

12. PROPERTIES OF ATENOLOL IUPAC NAME :- – 2-[4[2-hydroxy -3-(propan-2 ylamino) propoxy] phenyl] acetamide. CAS No.: 29122-68-7 MOLECULAR FORMULA : C 14 H 22 N 2 O 3 MOLECULAR WT : 266.336 g/mol MELTING POINT : 146-148 o C SOLUBILITY :- Freely soluble in methanol , soluble in acetic acid, DMSO, sparingly soluble in 96% ethanol. COLOUR :- white crystalline powder USES :- Anti- adrenergic ( beta-receptor), anti hypertension . 11/2/2017 12

13. org process research development 11/2/2017 13

14. org process Res Dev 1998,2,(4):274 11/2/2017 14

15. J. chem. Pharm.Res.,2012,4(1):375-382 11/2/2017 15

16. Chem pharm bulll1998,46,(3):505 11/2/2017 16

17. Atenolol Retrosynthesis 11/2/2017 17

18. SYNTHESIS OF ATENOLOL : proposed work 11/2/2017 18

19. IMPURITY Impurity are chemical substances inside a confined amount of liquid, gas, or solid, which differ from the chemical composition of the material or compound. Impurities are either naturally occuring or added during synthesis of a chemical or commercial product. 11/2/2017 19

20. Atenolol impurities by Europian pharmacopeia 11/2/2017 20

21. 11/2/2017 21

22. Atenolol impurity-G Compound name: atenolol impurity –G(EP) Chemical Name:- 2-[4-(2rs)-2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]acetic acid.. Molecular formula : C 14 H 21 NO 4 Molecular weight : 267.32 Appearance :- off white solid 11/2/2017 22

23. Retrosynthesis of impurity G 11/2/2017 23

24. Proposed Synthesis:- 11/2/2017 24

25. Atenolol impurity- F COMPOUND NAME:- atenolol impurity -F(EP) CHEMICAL NAME:- 2,2[(1- methylethy)iminobis(2-hydroxypropan-3,1- diyloxy-4,1-phenylene)] diacetamide MOLECULAR FORMULA: -C 25 H 35 NO 6 MOLECULAR WEIGHT:- 473.56 11/2/2017 25

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27. Synthesis of impurity F 11/2/2017 27

28. Experimental work 11/2/2017 28

29. SOLVENT SYSTEM :- 100 % PET ether 11/2/2017 29

30. SOLVENT SYSTEM :- 10% ETHYL ACETATE IN PET ether 11/2/2017 30

31. SOLVENT SYSTEM :- 10% ETHYL ACETATE IN PET ether 11/2/2017 31

32. SOLVENT SYSTEM :- 10% ETHYL ACETATE IN PET ether 11/2/2017 32

33. R efrences https://www.drugs.com/sfx/atenolol-side-effects.html https://www.researchgate.net/publication/260172609_Pharmaceutical_Impurities_An_Overview https://en.wi kipedia.org/wiki/Atenolol https://www.drugbank.ca/drugs/DB00335 http://drugsynthesis.blogspot.in/2011/11/laboratory-synthesis-of-atenolol.html Journal of chemical and pharmaceutical research, 2012, 4(1): 375-382. dJ ruparel college of arts science and commerce, mahim , mumbai . 11/2/2017 33

34. Journal of chemical and pharmaceutical research, 2012, 4(1): 375-382. dJ ruparel college of arts science and commerce, mahim, mumbai . Volume 3, issue 2, july-august 2010; article 012 impuritie and its importance in pharmacy Maejo int. j. sci. technol. 2012, 6(03),372-372 maejo international journal of science and technology Rasayan j.chem . Vol.6|no.2|april-june|2013 ISSN:0974-1496| e-ISSN: 0976-0083|CODEN:RJCABP http//www.rasayanjournal.com http//www.rasayanjournal.co.in 11/2/2017 34

35. Thank You 11/2/2017 35 Thank You