Drug design of Antihypertensive Agent-ppt

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Drug designing of Antihypertensive Agents :

Drug designing of Antihypertensive Agents Presented by :- Surya Narayana Parichha M.Pharm 3 rd semester (Pharmaceutical Chemistry) Govt. college of pharmacy, Aurangabad.


Contents What is Hypertension? What is drug designing? Major classes of Antihypertensive drugs Mechanism of action of ACE Inhibitor Designing of ACE Inhibitors –Captopril Therapeutic uses of Captopril References 2

What is Hypertension?:

What is Hypertension? Quantitative disorder of blood pressure regulation. Blood pressure – is the force of blood exerted on arteries as it flows through them. Classification of BP – Systolic – Diastolic (mm Hg) (mmHg) Normal <120 <80 Prehypertension 120-139 80-89 Stage 1 Hypertension 140-159 90-99 Stage 2 Hypertension >160 >100 3

What is drug designing?:

What is drug designing? Inventive process of finding new medications based on the knowledge of biological target. Other properties such as bioavailability , metabolic half-life, lack of side effects etc. are first optimized before the ligand can become a safe and efficacious drug. Two types 1. ligand based 2. structure based 4

Major classes of Antihypertensive drugs:

Major classes of Antihypertensive drugs Diuretics :- Thiazide type e.g.chlorothiazide, Bendroflumethiazide Diuretics :- Potassium sparing e.g. Spironolactone 5 9/21/2011


Cont… Beta blocker :- Non selective(beta-1/beta-2) e.g. Propanolol, ACE inhibitors:- e.g. captopril, enalapril Selective(beta-1):- e.g.- Atenolol 6


Cont… Calcium channel blocker :- e.g.-Nifedipine, Nicardipine Alpha adrenergic receptor antagonist :- e.g. Prazosin, Doxazosin, phentolamine Central sympatholytic :- e.g. Clonidine Miscellaneous agent :- e.g.-Reserpine, Hydralazine 7 9/21/2011

Mechanism of action of ACE Inhibitor:

Mechanism of action of ACE Inhibitor 8

Drug designing of ACE Inhibitors.:

Drug designing of ACE Inhibitors. Angiotensin-converting enzyme (ACE) is a zinc dependent metallopeptidase. 9 ACE Angiotensin I

Contd…. :

Contd…. Teprotide (a nona peptide), isolated from the venom of the Brazilian pit viper “ Bothrops jararaca ” by Ferreira et al. 10

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Development of captopril:

Development of captopril Began with the observations of D-2-benzylsuccinic acid, a potent inhibitor of Carboxypeptidase A. 12

Receptor binding :

Receptor binding 13 9/21/2011

Modification of captopril:

Modification of captopril The zinc binding group SH was replaced with a caboxilic acid or a phospinic acid. The phopinate and the carboxylate group was esterified to give orally bioavailable prodrugs i.e fosinopril and enalapril respectively. 14 Fosinopril

Therapeutic uses:

Therapeutic uses First line drug in all grade of hypertension. ACE inhibitors use in CHF patient, causes both arteriolar and venodilation. Use in treatment of Myocardial infarction. Prophylaxis in high cardiovascular risk; reduce risk of developing heart failure. In diabetic nephropathy; prevent or delay end-stage renal diseases. 15


Reference Manfred E. Wolff, Burger’s “Medicinal chemistry and Drug Discovery” vol.2 Therapeutic agent, 1994 pg. no- 264-314 Wilson and gisvolds “Textbook of organic medicinal and pharmaceutical Chemistry” vol. II pg.no-603-613 E.J. Ariens, Medicinal chemistry “A series of monograph” vol.11-x pg.no-146 K.D. Tripathi “Essentials of Pharmacology”,5 th edition 2008, pg- no.503 David A. Williams , Thomas L. Lemke Foye’s “Principle of Medicinal Chemistry” 6 th edition pg. no- 742-748 16


17 Thank you!

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