CARDIOVASCULAR AGENTS

Definition:
Cardiovascular agents are drugs, which are used in any way to treat conditions of
the heart or the circulatory or vascular system.
It increases the force and reduces the frequency of cardiac contractions. It improve
metabolism in cardiac-muscular tissue. They are used under medical supervision in
cases of heart failure and abnormal cardiac rhythm.
They are used in the treatment of angina, cardiac arrhythmias, hypertension,
erectile dysfunction, hyperlipidemias, and disorders of blood coagulation.
Also, they are used for their action on the heart or other parts of the vascular
system, to modify the total output of the heart or the distribution of blood to the
circulatory system.
Types:
I. Anti-anginal Agents and Vasodilators
II. Antiarrhythmic Drugs
III. Antihypertensive Agents
IV. Antihyperlipidemic Agents
V. Anticoagulants

I. ANTIANGINAL AGENTS AND VASODILATORS

Definition:
Antianginal drugs are directed mainly to alleviating and preventing anginal attacks
by dilating the coronary artery.
Vasodilators are used in the treatment of angina and congestive heart failure (CHF)
which is due to its ability to reduce peripheral vascular resistance.

DRUG CLASS: NITRATES OR NITROVASODILATORS

Definition: Agents that are molecules of esters of simple organic alcohols or polyols of
nitric acid
Structure Activity Relationship (SAR):
R O N
O

A. Amyl Nitrite
Synonyms: isoamyl nitrite, amyl nitrosum, nitramyl, amys, poppers
IUPAC Name: pentyl nitrite ; 1-nitropentane
Brand Name: Vaporole, Aspiral
Properties:
Yellowish liquid with an ethereal odor and a pungent taste
Volatile and inflammable at room temperature
Vapor forms an explosive mixture in air or oxygen
Nearly insoluble in water but is miscible with organic solvents
Synthesis: Preparation from amyl alcohol and HNO2 called esterification
Uses:
treatment for cyanide poisoning
used by inhalation or oral in alcohol solution
Industry:
neutralize odors in perfumes
cleaning agent and solvent
B. Nitroglycerin
Synonyms: Glyceryl trinitrate, glyceroli trinitratis, trinitroglycerin
IUPAC Name: 1,3-bis(nitrooxy)propan-2-yl nitrate
Brand Names: Transderm-Nitro, Nitro-Dur, Nitroderm, Glytrin, Deponit,
Dermatrans
Properties:
Colorless oil, with a sweet, burning taste
Slightly soluble in water, but it is soluble in organic solvents (volatile)
Synthesis: Prepared by carefully adding glycerin to a mixture of nitric and fuming
sulfuric acids
Uses:
stimulates the production of coronary collateral circulation
prevents experimental myocardial infarction by coronary occlusion (reduces
peripheral resistance during myocardial contractions)
decrease in cardiac work and reduce oxygen demand (reduces ventricular
volume, stroke volume, and cardiac output)
 Industry:
Used as an explosive in dynamite
Major component in double-based smokeless gunpowders by reloaders
C. Diluted Erythrityl Tetranitrate
Synonym: Erythritol tetranitrate
IUPAC Name: [(2R,3R)-1,2,4-trinitrooxybutan-2-yl] nitrate
Brand Name: Cardilate
Properties:
Solid, crystalline material
Very explosive
Slightly soluble in water and soluble in organic solvents
Synthesis: by nitrating erythritol by the mixing of concentrated sulfuric acid and a
nitrate salt
Uses:
For mild, gradual, and prolonged vascular dilation
Treatment of propylaxis attacks against angina and reduce blood pressure in
arterial hypertonia
Industry: For improvised detonation cord or homemade explosives
D. Diluted Pentaerythritol Tetranitrate
Synonyms: Pentaerythritol Tetranitrate, corpent, penthrite
IUPAC Name: 2,2-bis (hydroxymethy)-1,3-propanediol tetranitrate
[3-nitrooxy-2,2-bis(nitooxymethyl)propyl] nitrate
Brand Names: Peritrate, Pentritol
Properties:
White, crystalline material with a melting point of 140C
Insoluble in water, slightly soluble in alcohol, readily soluble in acetone
Synthesis: Formed in the nitric acid ester of the tetrahydric alcohol
pentaerythritol diluted with lactose, mannitol, or inert diluents
Uses:
Relaxes smooth muscle of smaller vessels in the coronary vascular tree
Used prophylactically to reduce the severity and frequency of angina attacks
Industry: Used as explosives
E. Diluted Isosorbide Dinitrate
Synonyms: Dinitrosorbide, Dinitroisosorbide
IUPAC Name: 1,4: 3,6-dianhydro-D-glucitol dinitrate
Brand Name: Isordil, Isoket
Properties:
White, crystalline powder
Water solubility is about 1mg/mL
Ease of hydrolysis
Synthesis: Prepared by dehydration of d-glucitol (sorbitol)
Use: Treatment or prophylaxis of acute angina attacks

Drug Class: Calcium Antagonists

Definition:
To reduce or prevent the increase of free cystosolic calcium ions by interfering the
transport of calcium ions through pores
These drugs are also known as calcium ion antagonists, calcium channel blocker,
slow channel blockers and calcium ion influx inhibitors
Inhibit movement of calcium ions into a cell membrane resulting vasodilation and
reduced blood pressure.
Structure Related Activity (SAR):

3
R O

4
O R

2 1
R N R

Drug Sub-Classes:
A. Phenylalkylamines
Definition: Calcium channel blocker that reduces myocardial oxygen demand and
reverse coronary vasospasms to treat angina
First generation:
a. Verapamil
 Synonym: Verapamilum
IUPAC Name: 5-[3,4-dimethoxyphenethyl)methylamino]-2-
(3,4dimethoxyphenyl-2-isopropylvaleronitrile
Brand Names: Calan, Isoptin, Covera
Properties:
Boiling point of 243-246 degrees
4.47 mg/L water soluble
Synthesis: The removal of HCl from the addition of 3,4- Dimethoxy -2-
isopropyl valeronitrile to 3,4-Dimethoxy phenyl ethyl - N - methyl -3-chloro
propyl amine
Uses:
Treatment of angina pectoris, arrhythmias from ischemic myocardial
syndromes, and supreventricular arrhythmias
Causes a change in the preload, afterload, contractility, heart rate, and
coronary blood flow
Reduces systemic vascular resistance and mean blood pressure
Second generation:
a. Anipamil *not included in book
b. Bepridil
Synonym: Bepadin
IUPAC Name: B-[(2- methylpropoxy)methyl]-N- phenyl-N-(phenylmethyl)-1-
pyrrolidineethylamine hydrochloride
Brand Name: Vascor
Properties:
24-50 hours half-life
Slightly soluble in water
Melting point at 128 degrees
Synthesis:
Isopropanol, epichlorohydrin, piperidine as a starting material, reaction
intermediate after thionyl chloride to obtain the target compound with
a substituted aniline, such as condensation
Bepridil will be synthesize via chlorination with SOCl2 and substituted
anilines
Uses:
prevents bradycardia
for stable angina

B. 1,4-Dihydropyridine
Definition: Calcium channel blockers used to reduce systemic vascular resistance
and arterial pressure
First generation:
a. Nifedipine
Synonyms: Nifedipinum
IUPAC Name: 1,4-dihydro-2, 6-dimethyl-4-(2- nitrophenyl)-3,5- pyridinedi-
carboxylate dimethyl ester
Brand Names: Adalat, Calcibloc, Procardia
Properties:
92-98% Protein binding
Half-life of 2 hours
Insoluble in water
Synthesis:
1. 2- Nitro benzaldehyde added to Methyl aceto acetate with the removal
of H 2O forming Methyl - [2-acetyl - 3-(2-nitrophenyl)] -2- propenoate
2. Ethyl aceto acetate (keto form) reversible to Ethyl aceto acetate forms
a Methyl -3- amino -2- butenoate
3. Methyl - [2-acetyl - 3-(2-nitrophenyl)] -2- propenoate added to Methyl
-3- amino -2- butenoate to a process called cyclisation releasing H20
forms nifedipine
Use: treatment of vasospastic angina as well as classic angina pectoris
Second generation:
a. Amlodipine
Synonyms:
IUPAC Name: 2-[(2-aminoethoxy)methyl]4-(2-chlorophenyl)-1,4-dihydro-6-
methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester
Brand Name: Norvasc
 Properties: Long half life (34 hours)
Synthesis:
N,N' - Dibenzyl ethanol amine added with Ethyl chloro aceto acetate
undergo condensation releasing HCl forming a keto form substance
reversible to a enol form. Then, it was added to o- Chloro benzaldehyde
and Methyl -2- amino -2- butenoate ( process: cyclisation with removal
of 2 moles of water). The product of cyclisation undergone
debenzylation removing 2 moles of C 6H5CH 2OH
Uses:
Treatment of chronic stable angina
Helps in the management of mild-to-moderate essential hypertension
b. Felodipine
Synonyms: Felodipina, Felodipinum
IUPAC Name: 4-2,3-dichlorophenyl)-1,4-di-hydro-2,6-dimethyl-3,5-pyridinedi
carboxylic acid ethyl methyl ester
Brand Name: Plendil
Properties:
High degree of protein binding
Half-life (10 to 18 hours)
Synthesis: Using the classical or modified Hantschz reaction such as
reaction of methyl 2-(2,3-dichlorobenzilenel) acetoacetate with ethyl 3-
aminocrotonate in t-BuOH for 96 hours at 25 degrees
Uses:
Treatment of chronic stable angina
Helps in the management of mild-to-moderate essential hypertension
c. Isradipine
Synonyms: Isradipino, Isradipinum
IUPAC Name: 4-(4-benzofuranazyl)-1,4-dihydro-2,6-dimethyl-3,5-
pyridinecarboxylic acid methyl 1-methylethyl ester
Brand Name: Dynacirc
Properties:
8 hours half-life
Practically insoluble in water
Synthesis:
The synthesis of the 1,4-dihydropyridine ring is quite classic, the first
step consists in a Knoevenagel reaction of methyl acetoacetate on the
benzoxadiazole 4-carboxaldehyde using piperidine and acetic acid as
catalyst and diisopropylether as solvent
The second step of this synthesis is the condensation of the acrylate
obtained with the isopropyl aminocrotonate in ethanol to give the
desire 1,4-dihydropyridine Isradipine after recrystallisation
Uses:
Treatment of stable angina
Reduces frequency of angina attacks
d. Nicardipine HCl
Synonyms: Nicardipino, Nicardipinum
IUPAC Name: 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-
pyridinedicarboxylic acid methyl 2-[methyl(phenylmethyl)amino]ethyl
ester hyrochloride
Brand Name: Cardene, Cardepine, Perdipine
Properties:
Water solubility of 2.2 mg/L
Melting point of 136-138 degrees
Synthesis: Preparation by mixing 2-
(Benzylmethylamino)ethyl acetoacetate, 3-Nitrobenzaldehyde and Methyl 3-
aminocrotonate
Uses:
Treatment of mild, moderate, and severe hypertension
Management of stable angina
e. Nimodipine
Synonyms: Nicardipino, Nicardipinum
IUPAC Name: 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-
pyridinedicarboxylic acid 2-methoxy-ethyl 1-methylethyl ester
Brand Name: Nimotop
Properties:
 1-7.9 half-life
Melting point of 125 degrees
Synthesis: synthesis of nimodipine is obtained by alkylation of sodium
acetate with 2-methoxyethyl chloride, Aldol condensation of meta-
nitrobenzene and the subsequent reaction of the intermediate with enamine
Uses:
Dilates the cerebral blood vessels
Treatment of subarachnoid hemorrhage-associated neurological deficits

C. Benzothiazepine
Definition: Calcium channel blockers that have both cardiac depressant and
vasodilator actions
First generation:
a. Diltiazem
Synonyms: Diltiazemum
IUPAC Name: (+)-cis-3-(acetoxy)-5- [2(dimethylamino)ethyl]-2,3- dihydro-2-
(4-methoxyphenyl)1,5- benzothiazepin-4(5H)one hydrochloride
Brand Name: Nimotop, Dilzem
Properties:
Half-life 3-4.5 hours
465ml/L water solubility at 25 degrees
Synthesis: prepared by N-alkylation of (+)-cis-3-hydroxy-2,3-dihydro-2-(4-
methoxyphenyl)-1,5-benzothiazepin-4(5H) -one with dimethylaminoethyl
chloride and K2CO3 in toluene/water, addition of a solubilizing agent and in
the presence of a phase-transfer catalyst, the toluene phase being directly
subjected to the final O-- acetylation
Uses:
treatment for angina pectoris
relieves coronary artery spasm and reduces myocardial oxygen
demand (decreasing heart rate and reducing overload)

DRUG CLASS: SODIUM CHANNEL BLOCKER

Definition: Drugs which impair conduction of sodium ions through sodium channels
Structure Related Activity (SAR):
O H
N
OH
N
R H

A. Ranozaline
Synonym: Ranozalinum
IUPAC Name: N-(2,6-dimethylphenyl)-2-[4- [2- hydroxy-3-(2-
methoxyphenoxy)propyl]piperazin- 1- yl]acetamide
Brand Name: Ranexa
Properties:
Very slightly soluble in water
7 hours half-life
Synthesis:
1. The acylation of 2,6-dimethylaniline (II) with chloroacetyl chloride in the
presence of triethylamine in dichloromethane affords N-(2,6-
dimethylphenyl) chloroacetamide (III), which is condensed with piperidine
(IV) in refluxing ethanol to yield N-(2,6-dimethylphenyl)-2-
piperazinoacetamide IV).
2. At last, this compound is condensed with 3-(2-methoxyphenoxy)-12-
epoxypropane (VI) in refluxing methanol toluene.
Use: the treatment of chronic angina

DRUG CLASS: ANTITHROMBOTIC AGENTS

Definition: Agents that play an important role in the pathogenesis of thromboses
Structure Related Activity (SAR):
Cl O

A. Aspirin
Synonyms: acetylsalicylic acid, acetylsalicylate
IUPAC Name: 2-(acetyloxy)benzoic acid
Brand Name: Aspilets, Bayer
Properties:
Boiling point 140 degrees and melting point 135 degrees
4600 mg/L water solubility
Colorless liquid
Synthesis:
From acetyl chloride and sodium salicylate
Reaction from salicylic acid and acetyl chloride
Synthetic salicin from meadowsweet
Use: irreversibly inhibits COX (prostaglandin H synthase) and thromboxane 2, an
inducer of platelet aggregation.
B. Dypiridamole
Synonyms: Dypiridamine, antistenocardin
IUPAC Name: 2,2,2,2-[(4,8-di- 1piperidinylpyrimido[5,4- d]pyrimidine-2,6-
diyl)dinitrilo]- tetrakisethanol
Brand Name: Persantin, triflusal
Properties:
Bitter, yellow, crystalline powder, soluble in dilute acids, methanol and
chloroform
Slightly soluble in water
Synthesis:
the reaction of 2,6-dichloro-4,8-dipiperidino-pyrimido(5,4-d)pyrimidine with
diethanolamine out at a very high temperature of 190 to 195C
Another is heating 2,6-dichloro-4,8-dipiperidino- pyrimido(5,4-d)pyrimidine
and diethanolamine at 155 to 160C under vacuum
Uses:
for long-term therapy of chronic angina pectoris
potentiates the effect of prostacyclin (PGI2)
for coronary and myocardial insufficiency
C. Clopidogrel
Synonym: Clopidogrelum
IUPAC Name: methyl ()-(S)--(2- chlorophenyl)-6,7- dihydrothieno[3,2- c]pyridine-
5(4H)- acetate sulfate
Brand Name: Plavix
Properties: Colorless to light yellow liquid
Synthesis:
1. Strecker reaction followed by esterification to give the methyl ester-6
addition of 2-chlorobenzaldehyde to a solution of sodium cyanide and
(1S)-1-(4-methoxyphenyl) ethanamine hydrochloride20 gave dia-
stereomerically pure (2S)-(2chlorophenyl){[(1S)-1-(4-
methoxyphenyl)ethyl]amino}acetonitrile HCl
2. Condensation of glycinate 6 with 2-(2-bromo-ethyl)-3-
(bromomethyl)thiophene-7 in the presence of N,N-diisopropylethylamine22
to give clopidogrel, fol-lowed by saltformation with sulfuric acid in
acetone gave enantiopure (S)-(+)-clopidogrel hydrogen sulfate
Uses:
inhibit the purinergic receptor located on platelets
antagonist to the P2Y2 receptor
for the preventative management of secondary ischemic events
D. Ticlopidine
Synonyms: Ticlopidina, ticlopidinum
IUPAC Name: 5-[(2-chlorophenyl)methyl]- 4,5,6,7-tetrahydrothieno [3,2-c]pyridine
hydrochloride
Brand Name: Ticlid
Properties:
Freely soluble
White, crystalline solid
 Melting point approx. 1189 degrees
Synthesis: by the action of thienyl lithium followed by cyclization
Use: reducing cardiac events in patients with unstable angina and cerebrovascular
events in secondary prevention of stroke
E. Eptifibatide
Synonyms: Intrifiban
IUPAC Name: 2-20[-carbamoyl-12-[4-(diaminomethylidenamino)butyl]-3-(1H-
indol-3- ylmethl)-2,5,11,14,22-hexaoxo-17,18-dithia-1,4,7,10,13,21-
hexazabicyclo[21,30] hexacosan-6-yl]acetic acid
Brand Name: Integrilin
Properties:
-2.3 hydrophobicity
MW: 839.36 g/mol
Synthesis: Based on natural product barbourin, a peptide isolated from the
venom of a pygmy rattlesnake (Sistrurus milarud barbouri)
Use: treatment of unstable angina and for angioplastic coronary interventions
F. Tirofiban
Synonyms: Tirofibanum
IUPAC Name: (2S-2-(butylsulfonylamino)-3-[4-(4-piperidin-4-
ylbutoxy)phenyl]propanoic
Brand Name: Integrilin, aggrastat
Properties:
White solid
223-225 deg C
Very slightly soluble
Synthesis:
Synthesized from piperidine ring and carboxylic acid
Found in the venom of the viper called Echis carinatus
Use: Treatment non-Q wave myocardial infarctionand unstable angina
G. Abciximab
Synonyms: c7E3 Fab
Brand Name: Reopro
Properties: Half-life (10 minutes)
Synthesis: Synthesized from chimeric Fab fragment monoclonal antibody
Uses:
Blocks the ability of fibrinogen to associate with the platelet
Treatment of unstable angina and adjunct to percutaneous coronary
intervention

II. ANTIARRYTHMIC DRUGS

Definition: Agents that are used most commonly affect impulse conduction by altering
conduction velocity and the duration of the refractory period of heart muscle tissue

Drug Class I Membrane Depressant drugs

Definition: Drugs that have membrane-stabilizing properties
Structure Related Activity (SAR):
NH2

A. Quinidine Sulfate, USP

Synonym: Quinidina
IUPAC Name: (S)-(Methoxyquinolin-4-yl)((2R,4S,8R)-8-vinylquinuclidin-2-yl)methanol
Brand Name: Cardioquine
Properties:
Crystallizes from water
In the form of fine, needle-like white crystals
Bitter and light sensitive
Aqueous solutions are nearly neutral or slightly alkaline
Soluble in 1% water and highly soluble in alcohol or chloroform
Synthesis: Sulfate of an alkaloid obtained from various species Cinchona and their
hybrids
Uses:
 reduces Na current by binding the open ion channels
treatment of supraventricular and ventricular ectopic arrhythmias
treatment of P. falciparum (malaria)
H. Quinidine Gluconate, USP
Synonyms: Quinidine D-gluconate
IUPAC Name: Cinchonan-9-ol,6-metoxy-,(9S)-,mono D-gluconate
Brand Name: Duraquin, Quinaglute
Properties:
freely soluble in water
high water solubility of the gluconate salt
odorless, very bitter, white powder
Use: used for injection (emergencies)
I. Quinidine Polygalacturonate
IUPAC Name: (S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2-2-2]octan-2-yl]-(6-
methoxyquinolin-4-yl)methanol
Brand Name: Cardioquin
Properties:
freely soluble in water
high water solubility of the gluconate salt
odorless, very bitter, white powder
Synthesis: formed by reacting quinidine and polygalacturonic acid in a hydroalcohol
Use: for arrhythmias
J. Procainamide Hydrochloride
Synonym: Procainamide
IUPAC Name: p-amino-N-[2- (diethylamino)ethyl]benzamide monohydrochloride
Brand Name: Pronestyl, Procan SR
Properties: Aqueous solutions of procainamide hydrochloride have a pH of about 5.5.
Synthesis: Synthesized by reacting 4-nitrobenzoic acid with N,N-(diethyl)ethyl
endiamine and reduction of nitro group
Uses:
decreases automaticity, decreases conduction velocity, and increases action
potential duration
for ventricular tachycardias
K. Disopyramide Phosphate
Synonyms: Disopyramida, Dysopyramidum
IUPAC Name: alpha-[2(diisopropylamino)ethyl]-alpha-phenyl-2-pyridine-acetamide
phosphate
Brand Name: Norpace
Properties:
50% plasma protein
Half-life (6.7 hours)
Synthesis: Synthesized by arylating benzalcyanide with 2-chloropyridine in the
presence of sodium amide and alkylation of a-phenyl-a-2-pyridyl acetonitrile with 2-
diisopropylaminoethyl chlorideusing sodium amide
Use: Treatment of refractory, life-threatening ventricular tachyarrythmias
L. Lidocaine Hydrochloride
Synonym: Lignocaine
IUPAC Name: 2-(diethylamino)-2,6- acetoxylidide monohydrochloride
Brand Name: Xylocaine
Properties:
White or slightly yellow crystalline powder
Very soluble in alcohol, ether and chloroform
Synthesis:
It starts with the reduction of 2,6-dimethylnitrobenzene to the dimethylaniline
by use of stannous chloride. The hydrochloric acid salt of dimethylaniline is
formed upon reduction of the nitro group and precipitates from the reaction
mixture
The substituted aniline is next converted to -chloro-2,6-dimethylacetanilide
by treatment with the bifunctional regent -chloroacetyl chloride
Uses:
as a standard parenteral agent for suppression of arrhythmias associated with
acute myocardial infarction and cardiac surgery (local anesthetic)
parenteral treatment of premature ventricular contractions
M. Phenytoin Sodium
Synonym: Fenitoin
 IUPAC Name: 5,5- diphenyl-2,4- imidazolidinedione, 5,5- diphenylhydantoin,
diphenyl- hydantoin sodium
Brand Name: Dilantin
Properties:
Fine, white, odorless, tasteless, almost crystalline powder
Soluble in acetic acid; slightly soluble in ethyl ether, benzene and chloroform
Synthesis:
1. benzaldehyde was separated from almond oil using Ca(OH)2 solution
2. 95% ethanol, benzaldehyde and a solution of sodium cyanide in water (150)
were mixed and cooled in an ice bath to obtain benzoin
3. Benzoin and concentrated nitric acid was added into it in a fumecupboard then
mized and solidified to form benzyl
4. Ethanol, benzyl, urea and sodium hydroxide pellets were refluxed then poured
in an ice bath and filtered. To the filtrate, concentrated sulphuric acid was
added then filtered
Uses:
depresses ventricular automaticity produced by digitalis, without adverse
intraventricular conduction
the control of grand mal types of epileptic seizure
treatment of digitalis- induced arrhythmias
N. Mexiletine Hydrochloride
Synonym: Mexiletina
IUPAC Name: 1-methyl-2-(2,6- xylyloxy)ethylamine hydrochloride
Brand Name: Mexitil
Properties:
203-205 deg C melting point
8.25 mg/mL water solubility
Half-life of 10 hours
Synthesis:
1. Synthesized by reacting the sodium salt of 2,6-dimethylphenol with
chloroacetone forming 1-(2,6-dimethylphenoxy)-2-propanone
2. 1-(2,6-dimethylphenoxy)-2-propanone is reacted with hydroxylamine gives
oxime
3. Oxime is reduced using hydrogen by Raney Nickel
Uses:
blocks the fast Na channel in cardiac cells
long-term oral prophylaxis of ventricular tachycardia
O. Tocainide Hydrochloride
Synonyms: Tocainida, Tocainidum
IUPAC Name: 2-amino-2,6-propionoxyxylidide hydrochloride
Brand Name: Tonocard
Properties: first-pass hepatic elimination after oral ingestion
Synthesis: by reacting 2,6-dimethyl aniline with 2-bromopropionic acid bromide
and substitution of bromine atom in the resulting amide with an amino group
Use: prevent or treat ventricular ectopy and tachycardia
P. Flecainide Acetate
Synonyms: Flecainida, Flecainidum
IUPAC Name: N-(2-piperidinylmethyl)-2,5-bis (2,2,2- trifluoroethoxy)benzamide
monoacetate
Brand Name: Tambocor
Properties:
228-229 deg c melting point
48.4 mg/mL water solubiltity
Synthesis: 2-Aminomethylpyridine (II) is condensed with 2,2,2-trifluoroethyl-2,5-
bis(2,2,2-trifluoroethoxy)benzoate (I) in refluxing glyme to produce 2,5-bis(2,2,2-
trifluoroethoxy)-N-(2-pyridylmethyl)benzamide (III), and the yielding product is then
hydrogenated with H2 over Pd/C in acetic acid
Uses:
for with local anesthetic activity
suppress chronic ventricular ectopy and ventricular tachycardia
Q. Moricizine
Synonym: Moracizine
IUPAC Name: ethyl 10-(3- morpholinopropionyl)phenothiazi ne-2-carbamate
Brand Name: Ethmozine
Properties: High affinity for inactive state
 Synthesis: phenothiazine derivative
Uses: treatment of malignant ventricular arrhythmias.
R. Propafenone
IUPAC Name: 2-[2-hydroxy-3- (propylamino)propoxy]-3- phenylpropiophenone
Brand Name: Rythmol
Properties: 20 % bioavailability
Synthesis:
involving initial formation of chalcone from o- hydroxyacetophenone was
superior over methods-2 with respect to yield and reaction process ;
the oxypropanolamine chain was built and then aldol condensation was
carried out
Uses:
Depresses the slow inward current of Ca2 ions
for acute termination or long- term suppression of ventricular arrhythmias

DRUG CLASS II BETA ADRENERGIC BLOCKING AGENTS

Definition:
Also called membrane-stabilizing or depressant effects on myocardial tissue
Inhibit cardiac response to sympathetic nerve stimulation by blocking the beta
receptors. This produces a reduction in heart rate, cardiac output and blood
pressure

Structure Related Activity (SAR):

Drug Class III - REPOLARIZATION PROLONGATORS

Definition: Drug that increases the effective refractory period of the membrane action
potential without altering the phase of depolarization or the resting membrane potential
Structure Related Activity (SAR):
CH3
N

R CH3

A. Amiodarone
IUPAC Name: 2-butyl-3-benzofuranyl-4-[2-(diethylamino)ethoxy]-3,5- diiodophenyl
ketone
Brand Name: Cordarone
Properties: Half- life of 25-30 hours
Synthesis : synthesized in the following manner. Benzofuran is acylated by
butyric acid anhydride in the presence of phosphorous acid, forming 2-
butyroylbenzfuran. Reduction of the carbonyl group in a WolffKizhner reaction
using hydrazine hydrate gives 2-butylbenzofurane. This is acylated with 4-
methoxybenzoic acid chloride, giving 2-butyl-3-(4-methoxybenzoyl)benzofuran),
which undergoes demethylation by pyridine hydrochloride, forming 2-butyl-3-(4-
hydroxy-benzoyl)-benzofuran (18.1.19). The resulting product is iodized in the
presence of potassium iodide, forming 2-butyl-3-benzofuranyl-4-(2-hydroxy-3,5-
diiodophenyl) ketone, which is reacted further with 2-diethylaminoethylchoride
Uses:
effective in maintaining sinus rhythm in patients who have been treated by
direct current shock for atrial fibrillation
lengthens the effective refractory period by prolonging the action potential
duration in all myocardial tissues
B. Bretylium Tosylate
IUPAC Name: (o-bromobenzyl)ethyl dimethylammonium p- toluenesulfonate
Brand Name: Bretylol
Properties:
Extremely bitter, white, crystalline powder
Freely soluble in water and alcohol
 Synthesis: synthesized by reacting o-bromobenzyltosylate with
ethyldimethylamine
Uses: use in ventricular arrhythmias that are resistant to other therapy (displaces
norepinephrine)
C. Dofetilide
IUPAC Name: N-[4-(3-{[2-(4-
methanesulfonylaminophenyl)ethyl]methylamino}propoxy) phenyl] methane-
sulfonamide
Brand Name: Tikosyn
Properties: High specificity for the delayed rectifier potassium currents (Ikr)
Uses:
acts by blocking the cardiac ion channel carrying the rapid component of the
delayed rectifier potassium currents
terminate supraventricular arrhythmias
prevent the recurrence of atrial fibrillation
treat life-threatening ventricular arrhythmias
D. Ibutilide
IUPAC Name: N-{4-[4-(ethylheptylamino)-1- hydroxybutyl]phenyl}methanesulfon
amide Brand Name: Corvert
Properties: No affinity for sodium and not high specific in Ikr
Use: for rapid conversion of atrial fibrillation or atrial flutter to normal sinus
rhythm
E. Sotalol
IUPAC Name: 4[1-hydroxy-2-(isopropylamino) ethyl]methylsulfonanilide
Brand Name: Betapace
Use: prolongs the duration of the action potential and, thus, increases the
effective refractory period of myocardial tissue
F. Azimilide
IUPAC Name: E-1-[[[5-(4-chlorophenyl)-2- furanyl]methylene]amino]-3-[4-(4-
methyl-1-piperazinyl) butyl]-2,4- imidazolidinedione
Brand Name: Betapace
Uses: blocks the delayed rectifier potassium current

DRUG CLASS IV: CALCIUM CHANNEL BLOCKERS

Definition: block the slow inward current of Ca2 ions during phase 2 of the membrane
action potential in cardiac cells
Structure Activity Relationship (SAR):

A. Verapamil
B. Diltiazem

III. ANTIHYPERTENSIVE AGENTS

Definition: agents for the treatment and control of hypertensive disease
Types of antihypertensive:
1. Endothelin Receptor Antagonists
2. Sympathetic Nervous System Depressants
3. Vasodilators
4. Calcium Channel blockers
5. Diuretics

DRUG CLASS: ENDOTHELIN RECEPTOR ANTAGONIST

Definition:
Agents that prevents Endothelin-1 for the regulation of smooth muscle contraction
Useful in treating hypertension, heart failure and coronary vasospasms
Structure Activity Relationship:
 O OH
N
H3C
N
O

A. Ambrisentan
IUPAC Name: (+)-(2S)-2-[(4,6- dimethyl-pyrimidin-2-yl)oxy]-3-mehoxy- 3,3-
propanoic acid
Brand Name: Letairis
Uses: treatment of pulmonary arterial hypertension (PAH)
B. Bosentan
IUPAC Name: N-[6-(2- hydroxyethoxy)-5- (2-methoxyphenoxy)- 2-pyrimidin-2-yl
pyrimidin-4-yl]-4- tert-butyl- benzenesulfonamide
Brand Name: Bozentan, Tracleer
Uses: works by competitively blocks endothelin receptor subtypes ETA & ETB
C. Sitaxsentan Sodium
IUPAC Name: N-[4-chloro-3-methyl-oxazol-5-yl)-2-[2-(6-methylbenzo[1,3]dioxol-5-
yl)acethyl]thiophene-3-sulfonamide
Brand Name: Thelin

DRUG CLASS: ADRENERGIC SYSTEM INHIBITORS (Sympathetic Nervous System

Depressants)
Definition: drugs that reduce BP by depressing activity of sympathetic nervous system
Structure Activity Relationship (SAR):

R
OH
O

*Agents Depleting Neurotransmitter Stores

A. Powdered Rauwolfia Serpentina
Brand Name: Raudixin, Rauserpal, Rauval, Benth (the whole root of R. Serpentina)
Properties:
light tan to light brown powder
sparingly soluble to alcohol & only slightly soluble in water
Synthesis: from natural source, Rauwolfia Serpentina
Uses:
treatment of mild or moderate hypertension or in combination with other
hypotensive agents in severe hypertension
Agents for the treatment for mentally deranged patients
B. Reserpine
IUPAC Name: methyl ester 2,11-dimethoxy-3-(3,4,5-trimethoxybenzoyloxy)-
yohimban-1-carboxylic
Brand Name: Serpasil, Reserpoid, Rau- Sed, Sandril
Properties:
white to light yellow, crystalline alkaloid
practically soluble in water
Synthesis: obtained from various species of Rauwolfia
Use: effective orally and parenterally for the treatment of hypertension.

*Guanethidine and Related compounds

C. Guanethidine Monosulfate
IUPAC Name: [2-(hexahydro-1 (2H-azocinyl)ethyl] guanidine sulfate
Brand Name: Ismelin Sulfate
Properties: White,crystalline material that is very soluble in water
Synthesis: Azocine is alkylated by chloracetonitrile, which forms 1-
azocinylacetonitrile, which is reduced by lithium aluminum hydride into
1-(2-aminoethyl)azocine (12.3.3). Reacting this with S-methylthiourea
Use: Produces a gradual, prolonged fall in blood pressure
D. Guanadrel Sulfate
IUPAC Name: (1,4-dioxaspiro[4.5]dec-2-ylmethyl) guanide sulfate
Brand Name: Hylorel
 Properties: Half-life of 10 hours
Synthesis: when cyclohexanone undergoes ketalization by 3-chloro-1,2-proandiol,
forming 2 chloromethyl-1,4-dioxyspiro[4,5]decane (12.3.5), which is further
akylated by sodium phthalimide. After alkyline hydrazinolysis, the resulting
phthalimide derivative (12.3.6) is transformed into 2-aminomethyl-1,4-
dioxyspiro[4,5]decane (12.3.7), which is reacted with S-methylthiourea
Use: Reduces elevated BP that prevents release of endogenous neurotransmitter
on nerve stimulation

*Selective adrenergic antagonists

D. Prazosin HCl
IUPAC Name: 1-(4-amino-6,7- dimethoxy-2- quinazolinyl)-4-(2- furoyl)piperazine
Brand Name: Minipress
Properties: Half-life of 2-3 hours
Synthesis: synthesized from 2-amino-4,5-dimethoxybenzoic acid, which upon
reaction with sodium cyanate undergoes heterocyclation into 2,4-dihydroxy-6,7-
dimethoxyquinazoline. Substituting hydroxyl groups of this compound with chlorine
atoms by reaction with thionyl chloride, or a mixture of phosphorous oxychloride
with phosphorous pentachloride gives 2,4-dichloro-6,7-dimethoxyquinazoline Upon
subsequent reaction with ammonia, the chlorine atom at C4 of the pyrimidine ring
is replaced with an amino group, which leads to the formation of 4-amino-2-chloro-
6,7-dimethoxyquinazoline. Introducing this into a reaction with 1-(2-
furoyl)piperazine
Use: ompetitively blocks postsynaptic 1- adrenoceptors of veins and arterioles
causing vasodilation.
E. Terazosin Hydrochloride
IUPAC Name: 1- (4-amino-6,7- dimethoxy-2- quinazolinyl)-4- (tetrahydro-2-
furoyl)piperazine monohydrochloride
Brand Name: Hytrin
Properties: Half-life of 12 hours
Synthesis: synthesized in exactly the same manner except using 1-(2-
tetrahydrofuroyl)piperazine instead of 1-(2-furoyl)piperazine
Use: Similar selective properties of specifically inhibiting a- adrenergic receptors
F. Doxazosin
IUPAC Name: 1-(4-amino-6,7- dimethoxy-2- quinazolinyl)-4-(1,4- benzodioxan-2-
ylcarbonyl)piperazine
Brand Name: Cardura
Properties: Half-life of 12 hours
Synthesis: synthesized from a Quinazoline compound
Use: useful in the management of hypertension associated with
pheochromocytoma

*Centrally acting adrenergic drugs

G. Methyldopate HCl
IUPAC Name: L3-(3.4- dihydrollyphenyl)-2- methylalanine)ethyl ester
hydrochloride
Brand Name: Aldomet, Methyldopa
Synthesis: An ester hydrochloride wherein the ester should be amine-free
Use: Lowers blood pressure by inhibiting the outflow of sympathetic
vasoconstrictor impulses from the brain
H. Clonidine Hydrochloride
IUPAC Name: 2-[2,6- dichlorophenyl)imino]imidazolidine monohydrochloride
Brand Name: Catapres
Synthesis: Derivative of the known alpha-sympathomimetic drugs naphazoline
and tolazoline
Use: As a nasal vasoconstrictors, approved to be effective in the treatment of mild
to severe hypertension
I. Guanabenz Acetate
IUPAC Name: [(2,6- dichlorobenzylidene)amino]guanidine monoacetate
Brand Name: Catapres
Synthesis: Derivative of the known alpha-sympathomimetic drugs naphazoline
and tolazoline
Use:
Reduces release of norephinephrine from the neuron
 Decreased symphatetic tone in the heart,, kidneys and peripheral blood
vessels
J. Guanfacine Hydrochloride
IUPAC Name: N-(aminoiminomethyl)-2,6-dichlorobenzeneacetamide
Brand Name: Tenex
Properties: Long duration of action
Synthesis: Structurally related to Clonidine HCl and Guanabenz acetate
Use: Acts as an agonist on central alpha2-adrenergic

DRUG CLASS: VASODILATORS

Definition: Agents for the treatment of angina and congestive heart failure (CHF) which
is due to its ability to reduce peripheral vascular resistance.
Structure activity Relationship (SAR):
N
N

NH
H2N

A. Hydralazine Hydrochloride
IUPAC Name: 1- hydrazinophthalazine monohydrochloride
Brand Name: Apresoline hydrochloride
Properties: Yellow crystals that is soluble in water and a pH of 3.5-4.5
Synthesis:
oxidative chlorination of phthalide with simultaneous hydrolysis of product,
which results in hydroxyphthalide which upon reaction with hydrazine
changes to phthalazone. This undergoes a reaction with phosphorous
oxychloride, forming 1-chlorophthalazine in which substitution of the chlorine
atom with hydrazine
Uses:
direct-acting vasodilator which acts predominantly on the arterioles
It reduces BP and peripheral resistance but produces fluid retention

DRUG CLASS: PHOSPHODIESTERASE TYPE 5 INHIBITORS

Defintion: Agents catalyze the hydrolysis of various cyclic nucleotides including cAMP
and cGMP or cAMP and cGMP interfere with the ability of myosin to be phosphorylated or
interact with actin. This results in muscle relaxation.
Structure Activity Relationship (SAR):
H3C

N
N
N
NH

H3C CH3

A. Sodium Nitroprusside
Synonyms: Nipride, Nipruton
Properties: extremely short half-life
Synthesis: reaction of potassium ferrocyanide with nitric acid, which forms
potassium nitroprusside which is further transformed to copper nitroprusside and
reaction of this with sodium carbonate gives sodium nitroprusside
Uses: used to lower blood pressure in hypertensive crises
B. Sildenafil Citrate
IUPAC name: 1-[4-ethoxy-3-(6,7- dihydro-1-methyl-7- oxo-3-propyl-1h-
pyrazolo[4,3- d]pyrimidin 5- yl)phenylsulfonyl]- 4-methylpiperazine citrate
Brand name: viagra
Uses: use in hypertension and angina pectoris. Little effect on angina and
unpredictable in managing hypertension. During phase 1 trial, patients noted that
there were improved effects in their sexual dysfunction
C. Vardenafil Hydrochloride
D. Tadalafil

DRUG CLASS: POTASSIUM CHANNEL AGONISTS

Definition: These drugs are also called Calcium channel openers. These agents activate
ATP-sensitive Potassium channels which leads to decrease of intracellular Ca.
Stucture Activity Relationship (SAR):
 1
R
CH3
O

2 O
R

Two Categories:
Azoxide used by intravenous injection as rapidly acting antihypertensive agent
for emergency reduction of blood pressure
Minoxidil the only direct-acting vasodilator that requires metabolic activation to
produce its antihypertensive effect

A. Diazoxide, USP
IUPAC Name: 7-Chloro-3-Methyl- 2h-1,2,4- Benzothiadiazine 1,1dioxide
Brand Name: Hyperstat IV
Synthesis: synthesized by condensating 2-aminosulfonyl-4-chloroaniline with
triethyl orthoacetate
Uses: Lowers peripheral vascular resistance, increases cardiac output and does
not comprise renal blood flow.
B. Minoxidil, USP
IUPAC Name: 2,4-Diamino-6- Piperidinopy- Rimidine-3-Oxide
Brand Name: Loniten
Synthesis: synthesized from barbituric acid, the reaction of which with
phosphorous oxychloride gives 2,4,6-trichloropyrimidine (22.8.1). Upon reaction
with ammonium, this turns into 2,4-diamino-6-chloropyrimidine (22.8.2). Next, the
resulting 2,4-diamino-6- chloropyrimidine (22.8.2) undergoes reaction with 2,4-
dichlorophenol in the presence of potassium hydroxide, giving 2,4-diamino-6-(2,4-
dichlorophenoxy)-pyrimidine (22.8.3).Oxidation of this product with 3-
chloroperbenzoic acid gives 2,4-diamino-6-(2,4-dichlorophenoxy)pyrimidine-3-
oxide (22.8.4), the 2,4-dichlorophenoxyl group of which is replaced with a
piperidine group at high temperature
Uses: relaxes vascular smooth musculature,thus, lowering systolic and diastolic
pressure

DRUG CLASS: POSITIVE INOTROPIC AGENTS

Definition:
Agents that successfully increase the force contraction of the heart may be
particularly useful in the treatment of CHF
Agents that increase the force of contraction allow greater amounts of blood to be
distributed through out the body.
Structure Activity Relationship (SAR):

R
A

Cardiac glycosides (Classes)

Cardenolides-possess an unsaturated butyrolactone ring.
Bufadienolides-have an -pyrone ring.

A. Digoxin
IUPAC Name: 3,14-dihydroxy-5-card-20(22)-enolide-3-rigitoxide
Brand Name: Lanoxin
Properties: Position 3 of the steroid is substituted wth three digitoxose residues
that, when removed, provide a genin or aglycone steroid that is still capable of
receptor binding but with altered pharmacokinetics
Synthesis: extracted form the leaves of Digitalis lanta, Digitalis orientalis, or
Scrophulariaceae
Uses: Widely use primarily a result of its fast onset reaction and short half-life
B. Digitalis
C. Amrinone
IUPAC Name: 3-amino-5-(4-piridinyl)-2(1H)-pyridinone (17.2.4), can be
synthesized from piridine-4-acetic acid
Brand Name: Inocor
Synthesis:
 reaction of which with a mixture of diemthylformamide-phosphorous
oxychloride gives 2-(4-piridyl)-3-dimethylaminoacrolein.Reacting this with
cyanoacetamide gives 3-cyano-5-(4-piridyl)-2(1H)-pyidinone. Hydrolysis of
the cyano group of this product gives 3-carbamyl-5-(4-piridyl)-2(1H)-
pyidinone. A Hofmann rearrangement of this product (using bromine in
sodium hydroxide)
acidic hydrolysis to the corresponding acid, 3-carboxy-5-(4-piridyl)-2(1H)-
pyridinone (17.2.5), nitration of which with nitrous acid in the presence of
sulfuric acid forms 3-nitro-5-(4-piridyl)-2(1H)-pyridinone (17.2.6). Reducing
the nitro group of this product with hydrogen
synthesized by condensing 2-(4-piridyl)malonaldehyde with cyanoacetamide
Uses: used for short-term treatment of cardiac insufficiency that does not respond
to treatment
of other drugs
D. Milrinone
IUPAC Name: 1,6-dihydro-2-methyl-6-oxo-(3,4-bipiridin)-5-carbonitrile
Brand Name: Primacor
Synthesis: methylated analogue of the intermediate product of amrinone
synthesis
Uses: also used for short-term treatment of cardiac insufficiency that does not
respond to treatment
of other drugs
D. Dopamine
IUPAC Name: 2-(3,4-dihydroxyphenyl)-ethylamine
Synthesis: synthesized from tyrosine forming 3,4-dihydroxyphenylanaline (DOPA)
is decarboxylated by the enzyme L-decarboxylase of aromatic acids
Uses: for CNS stimulant
E. Dobutamine
IUPAC Name: (_) 4-[2(4-hydroxyphenyl)-1-methylpropyl]-3,4-
dihydroxyphenylethylamine
Brand Name: Dobutrex.
Synthesis: by the reaction of 3,4-dimethoxyphenyl-2-amine and 1-(4-
methoxyphenyl)-3-butanone with a simultaneous reduction of formed imine, giving
the product, the methoxyl-protecting groups of which are cleaved by hydrogen
bromide
Uses: used in situations where, during severe cardiac decompensation, it is
necessaryto temporarily strengthen contractions of the myocardium, and in
particular during decompensation of cardiac activity associated with surgical
intervention on the heart or in organic diseases

DRUG CLASS: CALCIUM CHANNEL BLOCKERS (under anti-arrhythmic)

DRUG CLASS: DIURETICS (discussed on other chapter)

IV. ANTIHYPERTLIPIDEMIC AGENTS

Definition:
also called as Lipid-lowering drugs
agents for the treatment of atherosclerotic heart disease and hyperlipidemia

Structure Activity Relationship (SAR):

O
R
H3C CH3

HO O

A. Clofibrate
IUPAC Name: ethyl 2-(p- chlorophenoxy)-2- methylpropionate
Brand name: atromid-s
Properties: Stable, colorless to pale yellow liquid with a faint odor & a
characteristic taste.
 Synthesis: synthesized in a single-stage reaction from 4-chlorophenol, acetone,
and chloroform in the presence of an alkali, evidently by initial formation of
chlorethone-trichloro-tert-butyl alcohol, which under the reaction conditions is
converted into (4-chlorophenoxy)trichlorotert-butyl ether, and further hydrolyzed
to the desired acid 20.2.1, which is further esterified with ethanol in the presence
of inorganic acid
Uses: Drug of choice in txt of type iii hyperlipoproteinemias and also to a lesser
extent, in types iib and iv. Not effective for types I and IIA
B. Gemfibrozil
IUPAC Name: 5-92,5- dimethylphenoxy)-2,2- dimethylpentanoic acid
Brand Name: lopid
Synthesis: synthesized by alkylation 2,2-dimethylvaleric acid ethyl ester with 3-
(2,5 dimethylphenoxy)propylbromide-1 in the presence of lithium
diisopropylamide, or by oxidation of the corresponding aldehyde
Uses:
treatment of hyperlipoproteinemia in the mid 1970s
reduces plasma levels of VLDL triglycerides
stimulates the clearance of VLDL from plasma
C. Dextrothyroxine sodium
IUPAC Name: o-(4-hydroxyl-3,5- diiodophenyl)-3,5- diiodo-d-tyrosine mono sodium
salt hydrate
Brand Name: choloxin
Uses: Stimulates oxidative catabolism of cholesterol in the liver through
stimulation of 7-a- cholesterol hydroxylase
D. Cholestyramine resin
Brand Name: cuemid, questran
Synthesis: copolymer of divinylbenzene and styrene, which undergoes
chloromethylation and afterwards is reacted with triethylamine
Uses:
Useful in lowering plasma lipids
exchanges chloride ions for bile acids in the intestines
E. Colestipol hydrochloride
IUPAC Name: (C8H18N5)m(C3H6O)n
Brand Name: Colestid, Cholestabyl
Synthesis:hydrochloride of the product of copolymerization of epichlorohydrine
with diethylentriamine that contains varying numbers of quaternary nitrogen
atoms
Uses: It is also used to reduce stool volume and frequency, and in the treatment of
chronic diarrhea.
F. Colesevelam
IUPAC Name: allylamine polymer with 1-chloro-2,3-epoxypropane, [6-(allylamino)-
hexyl]trimethylammonium chloride and N-allyldecylamine, hydrochloride
Brand Name: Welchol, Cholestagel
Properties:
bile-acid sequestrants
a high-capacity bile acid-binding molecule.
Uses: It works in the bowel to help remove bile acids from the body. The body then
uses cholesterol to make more bile acids, which causes blood cholesterol levels to
decrease.
G. Nicotinic acid
IUPAC Name: 3-pyridinecarboxylic acid
Brand Name: niacin
Properties:
a water-soluble vitamin of the B complex occurring in various animal and
plant tissues.
It has PELLAGRA-curative, vasodilating, and antilipemic properties
Synthesis: synthesized industrially by heating a paraldehyde trimer of
acetaldehyde, under pressure with ammonia, which leads to the formation of 2-
methyl-5-ethylpyridine, followed by oxidation with nitric acid
Uses:
treatment of all types of hyperlipoproteinemias except type I
The drug reduces VLDL synthesis and LDL
H. Beta-sitosterol
Synonyms: Cupreol, Harzol, clionasterol
IUPAC Name: 22,23-Dihydrostigmasterol
 Brand Name: Stigmasterol
Uses: They are used to treat hyperlipidemias
I. Probucol
IUPAC Name: 4,4-(1- methylethylidine) bis(thio)bis[2,6- bis(1,1-
dimethylethyl)phenol]
Brand Name: lorelco
Synthesis: synthesized by thioketalizing acetone with 2,6-di-tert-butyl-4-
mercaptophenol in the presence of hydrogen chloride
Uses: Causes reduction of both liver and serum cholesterol levels
J. Ezetimibe
IUPAC Name: (3r,4s)-3-(4- fluorophenyl)-3- hydroxypropyl)-4-(4- hydroxyphenyl)-
2- azetidinone
Brand Name: Zetia
Uses:
antihyperlipidemic agent that has usefulness in lowering cholesterol levels
acts by decreasing cholesterol absorption in the intestine by blocking the
absorption of the sterol at the brush boarder.

DRUG CLASS: HMG-COA REDUCTASE INHIBITORS

Definition:
drugs that inhibit the enzyme HMG-CoA reductase
conversion of HMG-CoA to mevalonate in the synthetic pathway for the synthesis
of cholesterol

A. Lovastatin
IUPAC Name: 2-methylbutanoic acid 1,2,3,7,8,8a-hexahydro- 3,7-dimethyl-8-[2-
(tetrahydro-4-hydroxy6- oxo-2h-pyran-2- yl)ethyl]-1- naphthalenyl ester
Brand Name: mevacor
Properties: Obtained originally from the fermentation of fungi aspergillus terreus
& monascus ruber
Uses: Inhibits hmg- coa mevalonate to synthesis of cholesterol
B. Simvastatin
IUPAC Name: 2,2-dimethyl-8-[2- (tetrahydro-4-hydroxyl- 6-oxo-2-pyran-2-
yl)ethyl]-1- naphthalenyl ester
Brand Name: Zocor
Properties: highly bound to plasma proteins
Uses: Inhibits hmg- coa mevalonate to synthesis of cholesterol
C. Pravastatin
Brand Name: Pravachol
Properties: belongs to a group of drugs called HMG CoA reductase inhibitors, or
"statins."
Uses:
used to lower cholesterol and triglycerides (types of fat) in the blood.
used to lower the risk of stroke, heart attack, and other heart complications
in people with diabetes, coronary heart disease, or other risk factors
used in adults and children who are at least 8 years old.
D. Fluvastatin
E. Atorvastatin
IUPAC Name: [r-(r*,r*)]-2-(4- fluorophenyl)-b,d- dihydroxy-5-(1- methylethyl)-3-
phenyl- 4- (phenylamino)carbonyl]- 1h-pyrrole-1-heptanoic acid.
Brand Name: lipitor
Uses: management of high cholesterol and high blood pressure.
A. Rosuvastatin
Brand Name: Crestor
Uses:
used to lower cholesterol and triglycerides (types of fat) in the blood and to
slow the build-up of plaque (fatty deposits) in your blood vessels.
used to lower the risk of stroke, heart attack, and other heart complications
in certain people with diabetes, coronary heart disease, or other risk factors.
used in adults and children who are at least 10 years old.
B. Cerivastatin
Brand Name: Baycol
Uses:
blocks the production of cholesterol (a type of fat) in the body.
 used to reduce the amounts of LDL (bad) cholesterol and total cholesterol in
your blood.
reduces the amounts of triglycerides (another type of fat) and apolipoprotein
B (a protein needed to make cholesterol) in your blood and increases the
amount of HDL (good) cholesterol in your blood.

V. ANTICOAGULANTS
Definition:
agents which prevents RBC to create a clot
used in the prevention of arterial and venous thrombi in predisposed patients.
Its primary purpose is to prevent new clots from forming, or to impede the
extension of existing clots.

A. Protamine sulfate
Brand Name: Protamine Sulfate
Properties:
simple proteins of low molecular weight and strongly basic
occurs as fine white or off-white amorphous or crystalline powder
sparingly soluble in water
Uses:
Has an anticoagulant effect but if used in the proper amount
counteracts the action of heparin
B. Dicumarol
Synonyms: nicoumalone
Brand Name: Trombosan
Uses:
An oral anticoagulant that interferes with the metabolism of vitamin K.
It is also used in biochemical experiments as an inhibitor of reductases.
C. Warfarin
IUPAC Name: 3-(a- acetonylbenzyl)- 4-hydroxycoumarin sodium salt.
Brandname: Coumadin, Panwarfin
Properties: White, odorless, crystalline powder with a slightly bitter taste
Uses:
used in humans in i.v route for hypoprothrombinemia
for prophylaxis of or to treat venous thrombosis, atrial fibrillation with
embolism, ulmonary embolism and coronary occlusion
Industry: first very effectively as rodenticide (rats)
D. Anisindione
Brand Name: Miradon
Properties: White, crystalline powder, slightly soluble in water, tasteless, and
absorbed well after oral administration
Uses: Reduces the prothrombin activity of the blood.
E. Eculizumab
Brand Name: Soliris
Properties: binds to proteins in the blood that can destroy red blood cells in
people with genetic conditions that affect the natural defenses of red blood cells.
Uses:
used to prevent the breakdown of red blood cells in people with paroxysmal
nocturnal hemoglobinemia (PNH)
used to treat a rare chronic blood disease called atypical hemolytic uremic
syndrome (aHUS)

VI. SYNTHETIC HYPOGLYCEMIC AGENTS

Definition:
lowers the blood sugar level
treatment of non-ketosis-prone mild diabetes
stimulate the release of insulin from the fixing b-cells in the pancreas
Structure Activity Relationship (SAR):
R

+
S
HO O
HN O

HN
R
A. Tolbutamide
IUPAC Name: 1-butly-3-(p-tolysulfonyl)urea
Brand Name: orinase
Synthesis: reaction by interaction of p-toluenesulfonylamide (in the form of
sodium salt) with butylisocyanate
Uses: used only when the diabetic patient is an adult or shows adult- onset
diabetes
B. Chlorpropamide
IUPAC Name: 1-(p-chlorophenylsulfonyl)-3-propylurea
Brand Name: Diabinese
Synthesis: reacting p-chlorobenzenesulfonylamide with propylisocyanate
Uses:
oral diabetes medicine that helps control blood sugar levels
This medication helps your pancreas produce insulin
C. Tolazamide
IUPAC Name: 1-hexahydro-1H-azepin-1-yl)-3-(p-toluenesulfonyl)urea
Brand Name: Tolinase
Properties:
white or creamy-white powder
melting point of 165 to 173 C.
The solubility of tolazamide at pH 6.0 (mean urinary pH) is 27.8 mg per 100
mL.
Uses: an oral blood glucose lowering drug of the sulfonylurea class
D. Acetohexamide,USP
Brand Name:Diamox
Synthesis: reacting p-chlorobenzenesulfonylamide with cyclohexylisocyanate
Uses: used for the medical treatment of glaucoma, epileptic seizure, idiopathic
intracranial hypertension, altitude sickness, cystinuria, periodic paralysis,central
sleep apnea, and dural ectasia.
E. Glipizide
IUPAC Name: l-cyclohexyl-3-[[p-[2-(5-methyrpyrazine
carboxamido)ethyl]phenyl]sulfonyl]urea.
Brand Name: Glucotrol
Properties:
whitish, odorless powder
It is insoluble in water and alcohols, but soluble in 0.1 NNaOH
it is freely soluble in dimethylformamide
Synthesis: synthesized by a synthesis alternative to those described above. In the
given scheme, 6-methylpyrazincarboxylic acid is initially reacted with thionyl
chloride, resulting in the corresponding chloride, which undergoes further action
with 4-(2-aminoethyl)benzenesulfonamide, forming the corresponding amide. It is
then reacted in a traditional scheme with cyclohexylisocyanate
Uses: an oral blood-glucose-lowering drug of thesulfonylurea class.
F. Glyburide
IUPAC Name: 1-[4-[2-(5-chloro-2-methoxybenzamido)ethyl]-phenylsulfonyl]-3-
cyclohexylurea
Brand Name: Micronase
Properties: a white, crystalline compound
Synthesis: synthesized from 2-methoxy-5-chlorobenzoic acid chloride, which is
transformed into an amide 26.2.9 by reacting it with 2-phenylethylamine. This
undergoes subsequent sulfonylchlorination by chlorosulfonic acid, and then
amination by ammonia, which gives sulfonamide 26.2.10. The resulting
sulfonamide is reacted with cylclohexylisocyanate
Uses: used with a proper diet and exercise program to control high blood sugarin
people with type 2 diabetes
G. Glimepiride
IUPAC Name: 1-[[p-[2-(3-ethyl-4-methyl-2-oxo-3-pyrroline-1-
carboxamido)ethyl]phenyl] sulfonyl]- 3-(trans-4-methylcyclohexyl)urea
Brand Name: Amaryl
Properties: Contains a pyrrolidine system which is metabolized primarily through
oxidation of the alkyl side chain with the a minor metabolic route involving
acetylation of the amine.
Uses: used for: Treating type 2 diabetes in patients who cannot control blood
sugar levels by diet and exercise alone.
H. Gliclazide
 IUPAC Name: 1-(3-azabyciclo[3.3.0]oct-3-yl)-3- p-tolysulphonylurea
Brand Name: diamicron
Properties:
(pyrrolidine) increases its lipophilicity over that of tolbutamide (increases its
half life)
DRUG CLASS: NONSULFONYLUREAS-METAGLINIDES
Definition:
Oral hypoglycemic agents used in the management of type 2 diabetes (non-insulin
dependent diabetes mellitus ; secrete insulin from b-cells
Structure Activity Relationship (SAR):
R

NH
S
OH

A. Repaglinide
IUPAC Name :-(+)-2-ethoxy-4-[n-[3-methyl1(s)-[2- (1-
piperidinyl)phenyl]butyl]carbamoyl- methyl] benzoic acid
Brand Name: Prandin
Uses: oral blood glucose-lowering drug of the meglitinide class used in the
management of type 2 diabetes mellitus (also known as non-insulin dependent
diabetes mellitus or NIDDM).
B. Nateglinide
IUPAC Name: (-)-N-[(trans-4isopropylcyclohexane)carbonyl]-D-phenylalanine
Brand Name: Starlix
Uses: an oral antidiabetic agent used in the management of Type 2 diabetes
mellitus [also known as non-insulin dependent diabetes mellitus (NIDDM) or adult-
onset diabetes]
C. Rosiglitazone
IUPAC Name: (+-)-5-[[4-[2-(methyl-2- pyridinylamino)ethoxy]phenyl]me thyl]-2,4-
thiazolidinedione
Brand Name: avandia
Properties:
white to off-white solid
solubility decreases with increasing ph in the physiological range
D. Pioglitazone
Brand Name: Actos,Duetact
Properties:
odorless white crystalline powder
soluble in N,N-dimethylformamide, slightly soluble in anhydrous ethanol,
very slightly soluble in acetone and acetonitrile, practically insoluble in
water, and insoluble in ether
Uses: anti-diabetic drug (thiazolidinedione-type, also called "glitazones") used
along with a proper diet and exercise program to control high blood sugar in
patients with type 2 diabetes.
E. Metformin
IUPAC Name: n,n-dimethylimidodicarbonimidic diamide hcl
Brand Name: glucophage
Uses:
capable of reducing sugar absorption from the g.i tract
stimulate the release of insulin from the pancreas

DRUG CLASS: ALPHA-GLUCOSIDASE INHIBITORS

responsible for cleaving dietary carbohydrates & facilitating their absorption into
the body

A. Acarbose
 IUPAC Name: o-4,6-dideoxy-4- [[(1s,4r,5s,6s)4,5,6- trihydroxy-3- (hydroxymethyl)-
2- cyclohexene-1- yl]amino]a-d- glucopyranosyl-(1,4)- o-a-d-glucopyranosyl- (1,4)-
d-glucose
Brand Name: precose, glucobay
Synthesis: Naturally occurring oligosaccharide obtained from actinoplanes
utahensis
Uses: Acts as a competitive inhibitor, reduces the intestinal absorption of starch,
dextrin and dissacharides
B. Miglitol
rand Name: Glyset
Uses:
Miglitol is used along with a proper diet and exercise program to control high
blood sugar in people with type 2 diabetes. Controlling highblood
sugar helps prevent kidney damage, blindness, nerve problems, loss of
limbs, and sexual function problems.

VI. THYROID HORMONES

Definition:
dessicated, defatted thyroid substance has been used for many years as
replacement therapy in thyroid gland deficiencies ;iodine containing globulin
Structure Activity Relationship (SAR):
S
1
R
2
N R
2
R

A. Levothyroxine sodium
Brand Name: Synthroid, eltroxin, levoid, noroxin, syntroid,
Synthesis: synthesized in a multi-stage synthesis from 4-hydroxy-3-iodo-
5-nitrobenzaldehyde
Uses: Used in replacement therapy of decreased thyroid function (hypothyroidism)
B. Liothyroxine sodium
Brand Name: Cytomel
Uses: Treatment of metabolic insufficiency, male infertility, and certain
gynecological
.
VIII. ANTITHYROID HORMONES
Definition: treatment of hyperthyroidism; excessive production of thyroid hormones

A. Propylthiouracil
Brand Name: propacil
Properties:
Stable,white,crystalline powder with a bitter taste.
slightly soluble in water but readily soluble in alkaline solutions
Synthesis: synthesized by condensating ethyl butyroacetate with thiourea in the
presence of sodium ethoxide
Uses: treatment of hyperthyroidism
B. Methimazole
IUPAC Name: 1-methylimidazole- 2-thiol
Brand Name: tapazole
Synthesis:synthesized by reacting aminoacetic aldehyde diethylacetal with
methylisothiocyanate and subsequent hydrolysis of the acetal group of the
resulting disubstituted urea derivative 25.2.4 by a solution of sulfuric acid
Uses:
Txt of hyperthyroidism
Interferes with the activity of thyroid hormones already formed and stored in
the thyroid gland