Cholesterol-lowering drugs, Lipitor

Figure 20. A decline in serum cholesterol and low density lipoprotein (LDL) levels induced by the cholesterol-lowering drug, Lipitor, is paralleled by a decline in breath isoprene concentrations. Breath isoprene was measured by PTR-MS under carefully controlled conditions as described in the text. Replotted from data presented in Ref. [89], where two atypical samples ( ) are discussed.

Atorvastatm chloride (active ingredient in cholesterol-lowering drug Lipitor ) [38]... 

Many valuable compounds are aromatic in part, including steroids such as estrone and well-known pharmaceuticals such as the cholesterol-lowering drug alorvastatin, marketed as Lipitor. Benzene itself has been found to cause bone marrow depression and a consequent lowered white blood ceil count on prolonged exposure. Benzene should therefore be handled cautiously if used as a laboratory solvent. 

The cholesterol-lowering drug atorvastatin, marketed as Lipitor, is an example where biocatalysis research has been applied extensively and is in industrial use. The enzyme 2-deoxyribose-5-phosphate aldolase (DERA) has been a target of directed evolution for the production of atorvastatin intermediates [8,9,71]. DeSantis and coworkers [8,9] used structure-based... 

Baycol (cerivastatin, sold as Lipobay in Europe, Bayer) is a statin, a class of cholesterol-lower drugs. Statins are the most prescribed drugs in the United States, with more than 12 million people taking them, and more than 700,000 people in the United States taking cerivastatin. It received marketing approval on June 26, 1997 and was voluntarily removed from the market on August 8, 2001 because of its link to 100 deaths and several injuries from potentially the muscle disease rhabdomyolysis. The other statins — lovas-tatin (Mevacor Merck) pravastatin (Pravachol Bristol-Myers Squibb) simvastatin (Zocor Merck) fluvastatin (Lescol Novartis) atorvastatin (Lipitor Parke-Davis) rosuvastatin... 

Atorvastin (Lipitor, 13.40) is a cholesterol-lowering drug that has been synthesized as a single enantiomer through use of a chiral auxiliary (Scheme 13.6).16 Ester 13.36 contains the auxiliary, a chiral alcohol. Deprotonation of the ester forms an enolate (13.37). The enolate then attacks an aldehyde. The asymmetry of the stereocenter on the auxiliary causes the reaction to favor stereoisomer 13.38 over 13.39. Several recrystallizations are required to obtain 13.38 in high enantiomeric excess. Cleavage of the auxiliary from 13.38 and further manipulations of the side-chain afford atorvastin. 

Cholesterol and cholesterol-lowering drugs atorvastatin (Lipitor) and simvastatin (Zocor) (Section 29.8B)... 

Statins are a class of cholesterol-lowering drugs that affect serum cholesterol levels by a variety of mechanisms. Examples include Lipitor, Zocor, Pravachol, Lescol, and Mevacor. Recent evidence... 

Fig. 3. Chemical structures of HMG-CoA and several statin inhibitors of HMG-CoA reductase. Atorvastatin (Lipitor), simvastatin (Zocor), and pravastatin (Pravachol) are widely prescribed cholesterol-lowering drugs.

Site-specific mutated 2-deoxyribose-5-phosphate aldolase (DERA) was used as catalyst for the synthesis of the key intermediate useful for the preparation of the cholesterol lowering drug atorvastatin (Lipitor) (De Santis et al. 2003). 

Pfizer s atorvastatin (Lipitor) cholesterol-lowering drug... 

Atorvastatin calcium (35) is the adive compound of Lipitor that is used as cholesterol-lowering drug. The key motif of this derivative is ethyl (R)-4-cyano-3-hydroxybutyrate [73]. The authors proposed a two-step process that involved the use... 

Isis, in collaboration with Genzyme, is developing a cholesterol-lowering drug, mipomersen, which is a secrmd generation 2 -G-(2-methoxy) ethyl-modified ribose ON. Unlike conventional therapies, mipomersen acts directly on apoUpoprotein BlOO, instead of inhibiting HMG-CoA reductase (as does Lipitor). Recent data showed that the drug is able to dramatically reduce low density lipoprotein (LDL) levels but also caused an unexpected increase in liver enzyme levels above the... 

The study concerns the desymmetrization of the prochiral dinitrile (16) with preferential formation of the (Ji)-17, which was known to be a chiral intermediate in the synthesis of the cholesterol-lowering therapeutic drug (18) (Lipitor, Sortis, Torvast, etc.) as shown in Scheme 2.3. 

Ethyl 4-chloro-3-hydroxybutyrate (EHCB) is an important intermediate in the production of l-camitine and the cholesterol-lowering Pfizer drug Lipitor (see Chapter 31). The ruthenium catalyst, [Ru(p-cymene)I((S)-TMBTP)]+E, has been reported to reduce ethyl 3-chlorobutyrate in 97% ee with S/C ratios of 20,000 (Scheme 12.48).87,157 This chemistry has been reported at scales >100 kg.87... 

E. The statin class of drugs—Lipitor (atorvastatin), Mevacor (lovas-tatin), and Zocor (simvastatin)—is used to treat hypercholesterolemia. This class of drugs lowers cholesterol levels by inhibiting the biosynthesis of cholesterol. Specifically, these drugs inhibit the enzyme P-hydroxy-P-methylglutaryl-CoA (HMG-CoA) reductase, which catalyzes the reaction that converts HMG-CoA to mevalonate. This is the rate-limiting step of cholesterol biosynthesis. 

Lipitor is currently one of the best selling drugs for lowering cholesterol. Searching in WDI for Lipitor produces the page shown in Figure 10.1 [46]. The preferred name is Atorvastatin Calcium . WDI has information about the pharmacology, indications, interactions, and so on, hyperlinked for keyword search. 

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