1.To study chemistry, SAR, mechanism of action, side effects, therapeutic uses of various anti-hypertensive drugs.
2.To emphasize on the newer current upcoming drugs for the treatment of hypertension.
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Anti-hypertensive agent and Recent developements
1. Anti-hypertensive Agents And Recent Developments
Presented by:-
Mr. Naman Vijaykumar Jain
F.Y.M Pharm (Sem I)
Roll No- 23
Research Guide:-
Dr. (Mrs.) Deepali Amol Bansode
Associate Professor,
Department of Pharmaceutical Chemistry &
QAT
Department of Pharmaceutical Chemistry
Bharati Vidyapeeth University (Deemed to be),
Poona College of Pharmacy, Erandawane,
Pune-411038
Anti hypertensive agents and recent advances. 1
2. anti-hypertensive agents and recent advances. 2
Sr No Contents
1. Aim and objectives
2. Hypertension and types
3. Prevalence of hypertension
4. Renin angiotensin system
5. Anti-hypertensive agents
6. Recent advances in treatment of hypertension
7. Future advances for hypertension
8. Summary and conclusion
9. References
3. Aim :
To study different classes of anti- hypertensive drugs and overview the current new
approaches for the treatment.
Objectives :
1. To study chemistry, SAR, mechanism of action, side effects, therapeutic uses of
various anti-hypertensive drugs.
2. To emphasize on the newer current upcoming drugs for the treatment of
hypertension.
Anti-hypertensive agents and recent advances. 3
4. Hypertension
• Hypertension, also known as high or raised blood pressure,It is a condition in which the blood vessels
have persistently raised pressure.
• Hypertension or elevated blood pressure - is a serious medical condition that significantly increases the
risks of heart, brain, kidney and other diseases.
• Over time, if untreated, it can cause health conditions, such as heart disease and stroke.
Stages of Hypertension
Stages Systolic blood pressure Diastolic blood pressure
Normal <120 <80
Prehypertension 120-139 80-89
Stage 1 140-159 90-99
Stage 2 >160 >100
ANTI-Hypertensive agents and recent advances. 4
6. Prevalence of Hypertension
• As per WHO, in worldwide near about 1.13 billion peoples are suffering from hypertension.
• 1 in 4 men and 1 in 5 women are suffering from the hypertension.
• From 2012 to 2018,World health statistics has estimated that the prevalence of hypertension to be
29.2% in males and 24.8% in females.
anti-hypertensive agents and recent advances. 6
10. Diuretics
Hydrochlorthiazide
Chlorthalidone
Anti-hypertensive agents and recent advances. 10
Novel drug- Lixivaptan
General structure
Position Substitution Activity
C7 Sulfonyl Required for minimal pharmacological activity
N2 Alkyl group Substitution till propyl group sustain
pharmacological activity
C3 -H, -CH3 Gives potent pharmacological activity
S1 C=O Replacement of O=S=O by C=O gives potent
activity
C6 -CH3, -X Required for minimal pharmacological activity
Novel drug Lixivaptan is designed by
alteration in functional groups like
sulfoxide has been replaced by amide
functional groups replacement of
thiazide ring by benzopyrrolodiazepine
ring
12. Beta Blockers
Metaprolol
Propranolol
Anti-hypertensive agents and recent advances. 12
Position Substitution Activity
-Ar/Ph -Ar/Ph Required for minimal pharmacological activity.
-Ar/Ph Heterocyclic Gives more potent activity
Side
Chain
β-ethanolamine Required for minimal pharmacological activity.
Side
Chain
-OH Necessary for antihypertensive action.
-X -O- Gives potent action
Novel drug - Nebivolol
General structure
Nebivolol is the drug which differs structurally from other agents because it
contain 6-fluorochromane ring which is way more potent than propranolol,
atenolol, metaprolol.
Pindolol
Timolol
14. Anti-hypertensive agents and recent advances.
14
ACE Inhibitors
Position Substitution Activity
Pyrrolidine Pyrrolidine Required for minimal pharmacological activity.
Pyrrolidine Replace by heterocyclic compound Alters pharmacological activity e. g. Imidapril
-N Alkyl side chain Increased pharmacologic activity.
-C2 Carboxylic acid Required for minimal pharmacological activity.
-C2 Carboxylic acid Replacement with other functional group may alter the action e. g.
Alacepril
Captopril
Enalpril
Alacepril
Imidapril
Novel drug - Alacepril
General structure
16. Angiotensin II Receptor Blockers.
Losartan Irbesartan
Anti-hypertensive agents and recent advances. 16
• Angiotensin receptor blockers mostly used in that patients who are suffering from disease like :
1. Chronic kidney diseases
2. Heart failure
3. Kidney failure in diabetes
Novel drug- Fimasartan
18. Anti-hypertensive agents and recent advances. 18
Calcium Channel Blockers
General structure
Position Substitution Activity
1,4-Dihydropyriridine ring 1,4-Dihydropyriridine ring Required for minimal Pharmacological activity
N1
-H Required for minimal activity higher substitution decreases
the action
-R4
2-/ 4-nitro Decreases pharmacological activity. e. g. nifedipine
Amlodipine Nifedipine
Novel drug- Cilnidipine
20. Anti-hypertensive agents and recent advances. 20
Alpha Blockers
General structure
Position Substitution Activity
Quinazoline ring - Required for minimal pharmacological activity.
Quinazoline ring Replacement with Naphthalene ring Alteration in Pharmacological action.
C2
Piperazine ring Essential for minimal pharmacological action.
C6
, C7
Substitution with –OCH3 Essential for pharmacological action.
Piperazine ring Substitution with heterocyclic compound Potent Pharmacological action
Prazocin Terazocin
Novel drug- Naftopidil
21. Alpha II Receptor Agonist:
Anti-hypertensive agents and recent advances.
21
• It is a class of sympathomimetic agent that selectively
stimulate α adrenergic receptor.
• Alpha-adrenergic agonists have the opposite function of
alpha blocker.
• These agents in brain stem and in periphery inhibit
sympathetic activity and lowers the blood pressure.
• Example is Clonidine.
Clonidine Novel drug- Medetomidine
Vasodilators:
• Vasodilators are the agents that opens the blood vessels.
• Prevent the muscles from tightening and the walls from
narrowing, as a results blood flows through vessel very
easily .
• Commonly used vasodilators in the treatment of
hypertension is Hydralazine and the one of the novel drug
is Epoprostenol.
Hydralazine
Epoprostenol
22. Anti-hypertensive agents and recent advances. 22
Recent advances in antihypertensive agents
Sr. No. Name Structure
1 Selexipag
2 Riociguat
3 Treprostinil
31. Drug Mechanism Status Trial conducted by
BAY 94–8862 Mineral corticoid
antagonist
Phase 2 b Bayer
LCI699 Aldosterone synthase
inhibitor
Phase 3 trials Isturisa
BIA-5-453 Dopamine β hydroxylase
inhibitor
Phase 1 Bial
CYT006-AngQβ
(vaccine)
Vaccine against
angiotensin 2
Phase 2 Cytos Biotechnology
DIZE ACE 2 Activator Preclinical Zuche
Atryn Recombinant
Antithrombin
Phase 3 REVO Biologics
Future prospective of antihypertensive
Anti-hypertensive agents and recent advances. 31
32. Anti-hypertensive agents and recent advances. 32
Summary and Conclusion
• The presentation focuses on hypertension as an emerging disorder.
• There are various therapeutic agents are available, its chemistry and structural activity was
thoroughly explained along with the structural modifications.
• As per our findings the presentation opens a path for the newer drugs which may act as a
potent agents.
33. Hypertensive agents and recent advances. 33
References
1. https://en.wikipedia.org/wiki/Hypertension. (Accessed on 08/06/2021)
2. WHO ( https://www.who.int/health-topics/hypertension/) .(Accessed on 08/06/2021)
3. www.healthline.com.(Accessed on 08/06/2021)
4. www.sciencedirect.com (Elsevier) (Accessed on 08/06/2021)
5. www.healthygrades.com.(Accessed on 08/06/2021)
6. www.ncbi.nlm.nih.gov.hhs public access (Accessed on 08/06/2021)
7. https://medicine.Georgetown.edu/hypertension-drugs/(dept of medicine).(Accessed on
08/06/2021)
8. www.drugs.com (Accessed on 08/06/2021)
9. Https://Go.Drugbank.Com/ (Accessed on 08/06/2021)
10. Lemke TL, Williams DA, editors. Foye's principles of medicinal chemistry. Lippincott
Williams & Wilkins; 2012 Jan 24.
11. Wilson CO, Gisvold O, Block JH, Beale JM. Wilson and Gisvold's textbook of organic
medicinal and pharmaceutical chemistry/edited by John H. Block, John M. Beale Jr.
Philadelphia: Lippincott Williams & Wilkins,; 2004.
12. Korolkovas A. Essentials of medicinal chemistry. John Wiley & Sons; 2008 May 5.
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13. Oparil S, Schmieder RE. New approaches in the treatment of hypertension. Circulation research. 2019 Mar
13;116(6):1074-95.
14. Yao A. Recent advances and future perspectives in therapeutic strategies for pulmonary arterial
hypertension. Journal of cardiology. 2020 Nov 1;60(5):344-9.
15. Volpe M, Gallo G, Tocci G. New approach to blood pressure control: triple combination pill. Trends in
cardiovascular medicine. 2020 Feb 1;30(2):72-7.
16. Gradman AH, Vivas Y. New drugs for hypertension: Current hypertension reports. 2020 Sep 1;8(5):425-32.
Alomar SA, Alghabban SA, Alharbi HA, Almoqati MF, Alduraibi Y, Abu-Zaid A. Firibastat, the first-in-class
brain aminopeptidase a inhibitor, in the management of hypertension: A review of clinical trials. Avicenna
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17. Lindegaard Pedersen M, Krüger M, Grimm D, Infanger M, Wehland M. The prostacyclin analogue
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19. Yamamoto T, Niwa S, Ohno S, Onishi T, Matsueda H, Koganei H, Uneyama H, Fujita SI, Takeda T, Kito M,
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