Atorvastatin

C 33
H 35
F 1
N 2
O 5

Ball-and-stick Stick Space-filling

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76 atoms, 79 bonds.

IUPAC name: (3R,5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid
Molar mass: 558.650(81) g/mol
Atoms: 76
SMILES: CC(C)C1=C(C(=C(N1CCC(CC(CC(=O)O)O)O)C2=CC=C(C=C2)F)C3=CC=CC=C3)C(=O)NC4=CC=CC=C4
InChIKey: XUKUURHRXDUEBC-KAYWLYCHSA-N
PubChem CID: 60823

Made of

C H F N O

Structural formula of atorvastatin. Each unlabelled corner is a carbon atom, and the 25 hydrogens on carbon are not drawn. Wedges come toward you, hashes go back. It shows which atoms are joined to which, not the shape. The model above shows the shape.

Statins have been lowering LDL (low-density lipoprotein) cholesterol for decades, according to the US Food and Drug Administration (FDA), which names atorvastatin among them. The ChEBI database of chemical entities of biological interest files it as a synthetic statin. ChEBI also classes it as a pyrrole, an aromatic amide, a monofluorobenzene and a monocarboxylic acid with two hydroxyl groups. Its atoms are carbon, hydrogen, nitrogen, oxygen and a single fluorine.

PubChem’s systematic name for it opens with (3R,5R) and ends in 3,5-dihydroxyheptanoic acid. Read from that end, it describes heptanoic acid, a seven-carbon acid, with hydroxyl groups on carbons 3 and 5. Carbon 7 is bonded to the nitrogen of a pyrrole ring, and a long square bracket lists what that ring’s four carbons carry: 4-fluorophenyl, phenyl, phenylcarbamoyl and propan-2-yl groups. The Medical Subject Headings (MeSH) of the US National Library of Medicine call it a derivative of pyrrole and heptanoic acid.

Structure and bonding

Atorvastatin’s hub is a five-membered pyrrole ring of four carbons and a nitrogen, with a group on every corner. The nitrogen holds the acid chain; the carbons hold a fluorophenyl ring, a plain phenyl ring, an amide whose nitrogen bears a third benzene ring, and a three-carbon branch. Labels pick out the lone F on the corner of its ring farthest from the pyrrole.

In Ball-and-stick, each benzene ring shows three double bonds set between single ones. That is one fixed picture: the pi electrons are delocalised round each ring, above and below its plane, as in benzene. In the model’s computed geometry, all eighteen bonds of the benzene rings measure 1.395 Å.

Along the chain, the two carbons carrying OH groups each bond to four different groups, which makes them chiral, and the structural formula draws both OH bonds as wedges. The model ends the chain in the neutral acid, COOH with its hydrogen in place. The drug itself is atorvastatin calcium, the calcium salt in the National Cancer Institute’s (NCI) description, and PubChem calls the neutral acid the active part, or moiety, of that salt. Space-filling merges all 76 atoms into one bulky outline.

Where it turns up

Atorvastatin is sold on prescription only, as the ChEMBL database records. Atorvastatin calcium appears on FDA’s list of marketed prescription products approved for safety and effectiveness, as quoted by HSDB, the Hazardous Substances Data Bank. NCI’s drug dictionary gives Lipitor as the US brand name, CI-981 as a code name and atorvastatin calcium trihydrate as a synonym.

Its preparation rests on patents by B. D. Roth, a European one of 1991 and a US one of 1993, in HSDB’s record, and ChEMBL dates its first approval to 1996. The World Health Organization’s Model List of Essential Medicines includes it among lipid-lowering drugs.

The body metabolises it extensively, HSDB records, partly to ortho- and para-hydroxylated derivatives that inhibit its target enzyme in laboratory tests as strongly as the drug itself. The NORMAN Suspect List Exchange puts the added OH of two known human metabolites at position 2 or 4 of the amide’s phenyl ring.

Why it matters

Atorvastatin blocks HMG-CoA reductase, the liver enzyme that turns HMG-CoA, short for 3-hydroxy-3-methylglutaryl-coenzyme A, into mevalonate, a precursor of cholesterol and other sterols. NCI calls that conversion a key step in cholesterol synthesis, so blocking it cuts the cholesterol made in the liver. It adds a second effect: liver cells carry more LDL receptors, and so take up and break down more LDL.

MeSH has it lowering serum LDL cholesterol and triglycerides and raising HDL (high-density lipoprotein) cholesterol. It treats hyperlipidaemias (raised blood lipids) and prevents cardiovascular disease in patients with several risk factors. The National Heart, Lung, and Blood Institute (NHLBI) calls statins the most common medicine for high blood cholesterol. It reports studies in which statins reduced heart attack and stroke risk among people with high LDL cholesterol.

The active forms of every marketed HMG-CoA reductase inhibitor share a side chain of dihydroxy heptanoic or heptenoic acid, a study quoted by HSDB notes. In atorvastatin it is the 3,5-dihydroxyheptanoic acid at the end of its name, the stretch of the model that holds both chiral carbons.

Properties

Properties of atorvastatin Molar mass summed from IUPAC/CIAAW 2024 standard atomic weights; formula, atom and bond counts and PubChem's molecular weight from PubChem CID 60823.
Property	Value	Unit	Source
Molecular formula (Hill order)	C₃₃H₃₅FN₂O₅
Molar mass	558.650(81) g/mol	g/mol	IUPAC/CIAAW 2024
Carbon atoms	33
Hydrogen atoms	35
Fluorine atoms	1
Nitrogen atoms	2
Oxygen atoms	5
Bonds	79
Single bonds	66
Double bonds	13
PubChem molecular weight	558.6 g/mol	g/mol	PubChem

Safety

In July 2021 FDA asked for revised pregnancy information across the statin class, including removal of the contraindication against use in every pregnant patient. FDA calls a contraindication its strongest warning. Two reports in three class the pure chemical as a skin, eye and airway irritant that may harm breast-fed children, and one suspects damage to fertility or the unborn child. Those reports, from companies to the European Chemicals Agency, are gathered in the PubChem Laboratory Chemical Safety Summary for atorvastatin.

Questions

What does the 3D model of atorvastatin show?

It shows the neutral acid with all 76 atoms: 33 carbon, 35 hydrogen, five oxygen, two nitrogen and one fluorine, joined by 79 bonds. Four rings appear, a five-membered pyrrole and three benzene rings. Of the eleven C=C double bonds, three sit in each benzene ring and two in the pyrrole. Three O–H bonds belong to the two hydroxyl groups and the acid, and the single N–H to the amide.

Does atorvastatin dissolve in water?

Very little. Atorvastatin calcium trihydrate is very slightly soluble in distilled water and in phosphate buffer at pH 7.4, and insoluble in watery solutions at pH 4 and below, according to HSDB. The neutral acid has a log P, an octanol-water partition measure, of 3.76 in SangsterLogP's data. HSDB also gives a pK_a, a measure of acid strength, of 4.46 for the sodium salt.

What side effects can atorvastatin have?

The National Heart, Lung, and Blood Institute says statins usually cause none but may increase the risk of diabetes, mostly in people already at high risk. It names muscle damage and cognitive impairment as rare ones. LiverTox, the liver-injury database of NIDDK and NLM, links atorvastatin with mild, symptom-free rises in serum aminotransferases, enzymes that liver tests measure. These settle by themselves, and clinically evident acute liver injury is rare.

What label changes had FDA made for statins by 2015?

By 2015 FDA had concluded that statins rarely cause serious liver injury and that checking liver enzymes at regular intervals was of no use, so routine monitoring had left the labels. The revised labels also described possible non-serious, reversible side effects, among them memory loss and confusion and increased blood sugar.

Made of the same elements

C₁₇H₁₈F₃NO Fluoxetine 40 atoms, 41 bonds.