Chemistry Reference
In-Depth Information
Squalene
HO
Cholesterol
The formation of mevalonate is the rate-limiting step in cholesterol biosyn-
thesis. Drugs that inhibit HMG-CoA reductase are termed statins and are one
of the most widely used types of prescription drugs. All statins share a struc-
tural component that is similar to the 3-hydroxy-3-methylglutaryl portion of
HMG-CoA reductase. All statins differ from HMG-CoA in being more bulky
and more hydrophobic [10]. Statins occupy the binding site of HMG-CoA
thus blocking access of this substrate [11]. All statins share this common
mode of action but differ in their overall structural, biochemical, thermody-
namic, and pharmokinetic properties which influences their efficacy [12].
The first statins were launched by Merck with lovastatin (Mevacor
®
)
in 1987 and then simvistatin (Zocor
®
) in 1991. Bristol-Myers launched
pravastatin (Pravacol
®
) in 1991; Pfizer commercialized atorvastatin calcium
(Lipitor
®
) in 1997. As measured by annual sales, Lipitor is the most suc-
cessful drug in the history of the pharmaceutical industry [13]. Rosuvastatin
calcium (Crestor
®
) is AstraZeneca's top drug with $6.6 billion in annual
sales [14].
CO
2
Na
HO
HO
O
HO
O
HO
O
O
O
O
O
O
O
O
CH
3
CH
3
CH
3
H
3
C
H
3
C
H
3
C
Simvistatin
Lovastatin
Pravastatin
Ca
2+
Ca
2+
CO
2
CO
2
HO
HO
HO
HO
F
F
N
H
N
NN
O
NHSO
2
CH
3
2
Rosuvastatin calcium
Atorvastatin calcium
Search WWH ::
Custom Search