M.pharmacy 1 sem chemistry of natural product topic

1. CARDIOVASCULAR DRUG’S
Jaskaran walia

2.  CARDIOVASCULAR DRUG’S
Cardiovascular drug that are used to treat medical conditions associated with the heart or the
circulatory system (blood vessels), such as arrhythmias, blood clots, coronary artery disease,
high or low blood pressure, high cholesterol, heart failure.
 Antihyperlipidimic drug – drug which used for treatment of high level of fat ,such as
cholesterol in the blood. they are also called lipid lowering drug.
 Anticoagulant-chemical substance that reduce coagulation of blood prolonging the clotting
factor.
 ACE inhibitor- angiotensin converting enzyme inhibitor is used for the treatment of
hypertension and congestive heart failure.
 Antianginal drug- drug used in the treatment of angina pectoris, symptom of ischaemic heart
disease.
 Antiarrythmic drug- drug that are used to treat abnormal heart rhythm resulting from irregular
electrical activity of the heart.

3. .
LOVASTATIN
 Lovastatin is a cholesterol lowering agent that belong to class of medication called statin and
second agent of these class used for treatment of coronary heart disease.
 Discovered by Alfred alberts and his team at Merck in 1978
 lovastatin also know as Mevinolin was isolated from the fungi Aspergillus terrus, Oyster
mushroom and Red yeast rice.
 In 1980 the trial with ( Mevastatin) were suspended & because of some structure similarity
between Mevastatin and lovastatin, were also suspend and animal safety study initiated.
 In 1982 some small scale clinical investigation of lovastatin in very high risk patient were
taken which dramatic reduction LDL cholesterol were observed, with very few adverse effects.
 in 1987 lovastatin was approved by FDA, it was first statin approved by FDA.
 Lovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA
reductase), an enzyme that catalyzes the conversion of HMG-CoA to mevalonate, Mevalonate
is a required building block for cholesterol biosynthesis and lovastatin interferes with its
production by acting as a reversible competitive inhibitor for HMG-CoA, which binds to the
HMG-CoA reductase

4.  Key feature of lovastatin(A)
1.lactone ring 2.hexahydro naphthalene
3.Methylbutyl ester side chain
A B
 Branching at alpha carbon of methyl butyl ester side chain produce a compound which have more
intrinsic activity, e.g.- simvastatin (B)
 Lovastatin is synthesized from biosynthetically precursor monacolin.

5. .
A. Simvastatin and lovastatin itself a Prodrug which in vivo metabolized to produce active derivative B-
hydroxy acid derivative (active form).
B. Pravastatin (1) is open hydroxy acid derivative. Launched by Sankyo and Squibb in 1989. produce by
microbial biotransformation of Mevastatin.
C. Substitution of Hexahydronapthalene moiety with 4-fluoro phenyl substituted heterocyclic ring produce several
new product Fluvastatin,(2) atorvastatin.(3) Etc. The latest member of this group of cholesterol-lowering drugs
Rosuvastatin to be launched in 2002
1 2 3

6. .
DICOUMAROL
1.Dicoumarol is a anticoagulant compound, Dicoumarol is a natural chemical substance of combined plant
and fungal origin.
2.In 1922 there appered a report on a disease of cattle in the plain of Dakota and Canada characterized by
interal bleeding. It was traced to ingestion of spoiled sweet clover hay.
3.In 1939 campell and link identify the hemorrhagic agents as Dicoumarol
4.The biological synthesis during spoilage can bi rationalized an oxidation of coumarin to 4-hydroxy
coumarin which upon coupling with formaldehyde lead to Dicoumarol.
5.They act by inhibiting synthesis of vitamin k depended clotting factor in liver.
Coumarin Dicoumarol


7. Dicoumarol as lead compound
1.Coumarin and 4- hydroxy coumarin do not possess anticoagulant activity.
2. The coumarin structure is derived from cinnamic acid via ortho-hydroxylation, trans- cis isomerisation of the side
chain double bond and lactonisation.
3. 4-hydroxycoumarin residue substituted at the 3-position, proved essential for biological activity.
4. 4-hydroxycoumarin derivative that was longer acting and more potent than Dicoumarol.
5. Dicoumarol had a slow, erratic onset of action.
6.Benzopyran 2 –one 4-hydroxy-3-(3-oxo-1phenylbutyl) coumarin (warfarin) derivate of coumarin.
7 The S (-) isomer is about 5 - 8 times more potent than the R (+)isomer; however, commercial warfarin is a racemic
mixture.
Warfarin Acenocoumalone

8. TEPROTIDE
1.Teprotide is nonapeptide which has been isolated from the snake Bothrops jararaca.
2.The antihypertensive effects of teprotide were first observed by Sergio Ferreira in 1965
3. it was first isolated by Ferreira along with eight other peptides in 1970.
4.Teprotide was synthesized in 1970 and from there its antihypertensive properties were studied
more closely.
Pyr -Trp-Pro-Arg -Pro- Gln-Ile-Pro-Pro

9. 1.Carboxyalkanoyl and mercaptoalkanoyl derivatives of proline were found to act as potent,
specific inhibitors of ACE.
2. Teprotide was a lead compound is developed of captopril, & and other orally active
antihypertensive drug.
Proline Captopril Lisinopril

10. Thank you