Organic Compound- atorvastatin

The term atorvastatin refers to a class of medications known as HMG-CoA reductase statins or inhibitors (Doggrell 3). Most specifically, atorvastatin plays a significant part in lowering the amounts of toxic triglycerides in the blood as well as cholesterol such as LDL or low-density lipoprotein. In addition, they raise levels of beneficial cholesterol such as HDL (high-density lipoprotein). Prabhu and Patravale (1) write in their paper that it is used to reduce the risk of stroke and treat elevated cholesterol, heart disease, and other heart problems in people with type 2 diabetes (Doggrell 5). Moreover, the atorvastatin also helps in treating some of other risk factors including the coronary heart disease (O’Malley 4). Markedly, the compound is used in children who are at least ten years of age and adults.

Chemical Structure of the Atorvastatin Compound

In light of decreasing the risk of stroke and heart attack, the atorvastatin compound helps in improving the levels of cholesterol (O’Malley 5). Its structure makes it more useful in weight loss, diet, and exercising (Doggrell 6). Essentially, the drug aims at preventing the cholesterol from piling up in the arteries. Note that the clogged arteries can easily block the flow of blood to the brain and heart. Atorvastatin comes in the form of the tablet that people take by mouth.

Figure 1: The Chemical Structure of Atorvastatin

Remember that atorvastatin is readily available in either generic shape or brand-name drug known as Lipitor. Such a drug must never be used during pregnancy since it can result in causing harm to the unborn babies (O’Malley 6). Mostly, it can also cause side effects that are very serious. Specifically, such effects include the breakdown of muscles, also known as rhabdomyolysis or myopathy (Doggrell 8). Senior people are at risk of such effects especially if they have problems with controlled thyroid or the problems of the kidney. A person has to see a doctor immediately if things such as tenderness, the pain of the muscle, or weakness start to occur.

IUPAC Name of Atorvastatin

Chemical/ Physical Properties

Basicity/ Acidity

Atorvastatin is a heptanoic and pyrrole acid derivative (Doggrell 9). It can function as both weak bases (acceptors of protons) and weak acids (donors of protons). In most cases, atorvastatin is used in combination with ezetimibe and bile acid to increase the reduction levels in cholesterol.

Nucleophilic/ Electrophilic Sites

In atorvastatin, the reaction of aldol plays a significant role in uniting two relatively simple molecules into one that is more complex (O’Malley 8). At this point, the increased complexity results from the two new stereogenic centers (Prabhu and Patravale 7). Note that several nucleophiles may be employed in the reaction of the compound. Specifically, such nucleophiles include enolates, enols, and ketones’ enol ethers.

Chirality

It is noted that the first atorvastatin synthesis happened during the discovery of drugs following the separation of chiral chromatography of the enantiomers (Doggrell 10). In effect, the chiral auxiliary significantly contributes in setting the stereochemistry of the two functional groups of alcohols through the idol reaction.

Intermolecular/ Intermolecular Forces

In atorvastatin, the bonds of hydrogen have directionality in that the groups of acceptors and donors are oriented properly with respect to each of the other bonds of hydrogens to form. In this case, the intermolecular forces help the atorvastatin to binds to the enzyme in preference to the huge number of other targets of potential enzymes (Prabhu and Patravale 9). Essentially, both the complementary pattern and shape of the hydrogen bonding plays a significant role of ensuring the compound to the HMG-CoA reductase (Prabhu and Patravale 10). As a result, the atorvastatin inhibits its capability to speed up the mevalonate formation.

Label Function Groups

In practice, the label function groups of atorvastatin consist of two alcohols connected via an idol reaction. According to Doggrell (11), the process chemistry develops a scalable and cost-effective synthesis once the compound enters the process of pre-clinical development. In this case, the overall synthesis key element is to ensure stereochemical purity in the final substance of drug.

Figure 2: Label Function Groups of Atorvastatin

Interesting Physical Properties

Interestingly, atorvastatin has a molecular weight of 558.65g/ mol. Moreover, it made of a hydrogen bond donor count of 4. In the same way, the compound is also made of six hydrogen bond acceptor count (Doggrell 12). In addition, its complexity value is 822 with a rotatable bond count of twelve (Prabhu and Patravale 14). Physically, the compound is stable in nature with a melting point that ranges between 159.2 to 160.7oC. It is also noted to be soluble in water with a pH value of 2.1.

The Use of the Compound

As already noted, atorvastatin has several uses (Prabhu and Patravale 15). Note that the compound is used along with a special diet with a primary intention of lowering the fats such as triglycerides and LDL. In effect, it raises the good cholesterol in the body such as HDL in the bloodstream (O’Malley 9). Besides, eating the proper diet like low-fat or the low-cholesterol diet, some of the other changes in the lifestyle that helps the type of medication work better include losing weight for the overweight ones, exercising, and stop smoking.

History of the Compound

In 1982, Warner-Lambert hired Bruce Roth as the chemist with the main reason of synthesizing an experimental compound. Such compound was later referred to as the atorvastatin (Prabhu and Patravale 16). According to the Warner-Lambert, the atorvastatin was a version of me-too of the rival orphan drug lovastatin of Merck & Co. In 1985, Bruce Roth and his bosses, Ronal Creswell and Roger Newton managed to convince the executives of the company to move the atorvastatin into the expensive clinical trials (Doggrell 13). The simvastatin was compared with the atorvastatin, and the early results proved that the compound had more potent with fewer side effects (Prabhu and Patravale 17). Under the name Lipitor, this compound becomes the best-selling drug in the world of all time.

Compound Mode of Operation

Atorvastatin, as with other statins is a competitive inhibitor of the reductase of HMG-CoA. However, unlike most others, it is a complete compound of synthetic (Doggrell 14). Recent studies prove that high-dose statin treatment in patients who suffer from acute coronary syndrome may act as a plaque-stabilizing role (Prabhu and Patravale 19). Nonetheless, statins have anti-inflammatory effects at high doses. Moreover, it increases the necrotic plaque core reduction, and improve the functionality of endothelial (Doggrell 15). In effect, the process results in the stabilization of plaque and some cases the regression of plaque.

Works Cited

Doggrell, Sheila. “Is Atorvastatin Superior to Other Statins? Analysis of the Clinical Trials with Atorvastatin Having Cardiovascular Endpoints”. Reviews on Recent Clinical Trials, vol. 1, no. 2, 2006, pp. 3-15. Bentham Science Publishers Ltd., doi:10.2174/157488706776876508.

O’Malley, P. “Atorvastatin At 80 Mg/Day Reduced Cerebrovascular Events More Than Atorvastatin At 10 Mg/Day in Stable Coronary Heart Disease”. Evidence-Based Medicine, vol. 12, no. 2, 2007, pp. 4-13. BMJ, doi:10.1136/ebm.12.2.43.

Prabhu, Priyanka, and Vandana Patravale. “Dissolution Enhancement of Atorvastatin Calcium by Co-Grinding Technique.” Drug Delivery and Translational Research, 2015, Springer Nature, doi:10.1007/s13346-015-0271-x.