CID 156391

C₁₄H₁₄O₃

Naproxen

C 14
H 14
O 3

Ball-and-stick Stick Space-filling

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31 atoms, 32 bonds.

IUPAC name: (2S)-2-(6-methoxynaphthalen-2-yl)propanoic acid
Molar mass: 230.263(34) g/mol
Atoms: 31
SMILES: CC(C1=CC2=C(C=C1)C=C(C=C2)OC)C(=O)O
InChIKey: CMWTZPSULFXXJA-VIFPVBQESA-N
PubChem CID: 156391

Made of

C H O

Structural formula of naproxen. Each unlabelled corner is a carbon atom, and the seven 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.

Naproxen’s two fused rings can be numbered from either end. ChEBI, the Chemical Entities of Biological Interest database, calls the molecule a methoxynaphthalene: 2-methoxynaphthalene carrying a carboxyethyl group at position 6. PubChem’s IUPAC name, (2S)-2-(6-methoxynaphthalen-2-yl)propanoic acid, numbers the other way, putting the methoxy group at 6 and the acid chain at 2. The NCI Drug Dictionary describes the molecule, built from carbon, hydrogen and oxygen, as a propionic acid derivative and a nonsteroidal anti-inflammatory drug, or NSAID.

HSDB, the Hazardous Substances Data Bank that PubChem quotes, describes the pure acid as a crystalline powder, white or close to it and practically odourless, melting at 155 °C. It hardly dissolves in water but dissolves freely in alcohol; naproxen sodium, the salt, does the reverse. MeSH, the Medical Subject Headings index, records both as medicines, and the model draws the neutral parent acid of PubChem’s record.

Structure and bonding

One carbon just outside the rings holds four different partners: hydrogen, a methyl group, the ring system and the carboxylic acid group. Chem1 calls such a carbon chiral: it can take two different three-dimensional forms, enantiomers. The (2S) at the head of PubChem’s name is the form the model draws, the configuration HSDB calls the effective isomer. HSDB records that form being obtained from the mixture of both; PubChem’s ibuprofen record is the mixture itself.

Ball-and-stick shows ten ring carbons joined by five double and six single bonds, lying flat with the methoxy group in their plane. Chem1 calls such alternation a conjugated system, its double bonds’ second electron pairs spread along the whole stretch, as in naphthalene. Every ring bond in the model comes close to 1.4 Å, drawn single or double. Space-filling turns the ring system into a long, flat slab.

Labels mark the acid group’s two oxygens and the hydrogen on one of them: the neutral acid. HSDB puts naproxen’s pK_a at 4.15: the pH at which, in Chem1’s terms, acid and conjugate base stand equal. Above that pH most dissolved naproxen has lost the hydrogen as naproxen(1−), the anion of naproxen sodium.

Where it turns up

LiverTox, the liver-injury database of NIDDK and NLM, counts naproxen among the popular over-the-counter NSAIDs, used widely for mild to moderate pain and for arthritis. It is sold under names such as Naprosyn. HSDB lists the salt for the minor aches of colds, headache, toothache, sore muscles and backache. Acid and salt alike serve for pain after surgery, dental surgery included, after childbirth, with periods and with migraine. ChEBI adds osteoarthritis, gout, ankylosing spondylitis, tendinitis and bursitis.

Horses receive it as well, against the inflammation, pain and lameness of arthritis, and US federal law restricts that product to use by a licensed veterinarian or on one’s order. ChEBI also lists naproxen as an environmental contaminant and a drug allergen. US Consumer Product Safety Commission rules require special packaging for some naproxen preparations for human use.

Why it matters

Naproxen blocks both cyclo-oxygenase enzymes, COX-1 and COX-2, cutting the precursors of prostaglandins and thromboxanes, compounds the body makes with those enzymes. The NCI Drug Dictionary credits the fall in prostaglandins with its medical effects, and less thromboxane A₂, explained under aspirin, leaves platelets slower to clump. By HSDB’s account it also steadies lysosome membranes and damps the response of neutrophils, white blood cells, to signals that draw them in. Its exact mechanisms, HSDB notes, are not settled.

HSDB cites evidence that primary dysmenorrhoea, a form of period pain, is also driven by prostaglandins, and that naproxen has eased it, probably by holding back their formation. In arthritis it relieves symptoms but has not been shown to halt or reverse the disease. In the liver much of it becomes 6-desmethylnaproxen, and LiverTox links the drug to rare cases of clinically apparent liver injury.

HSDB traces its making from 2-naphthol through a Friedel-Crafts acylation and a Willgerodt-Kindler reaction. J. H. Fried and I. T. Harrison patented the preparation from 1968. ChEMBL, a drug database, dates its first approval to 1976.

Properties

Properties of naproxen Molar mass summed from IUPAC/CIAAW 2024 standard atomic weights; formula, atom and bond counts and PubChem's molecular weight from PubChem CID 156391.
Property	Value	Unit	Source
Molecular formula (Hill order)	C₁₄H₁₄O₃
Molar mass	230.263(34) g/mol	g/mol	IUPAC/CIAAW 2024
Carbon atoms	14
Hydrogen atoms	14
Oxygen atoms	3
Bonds	32
Single bonds	26
Double bonds	6
PubChem molecular weight	230.26 g/mol	g/mol	PubChem

Safety

The US Food and Drug Administration (FDA) concluded in April 2005 that it could not treat naproxen as free of added risk to the heart and blood vessels. The same review recommended a boxed warning for every prescription NSAID, naming that risk and serious, often life-threatening gut bleeding; ChEMBL records one for naproxen. As a pure chemical it carries the signal word Danger, with classifications from harm if swallowed to suspected damage to fertility or the unborn child. The PubChem Laboratory Chemical Safety Summary for naproxen gathers them.

Questions

What does the naproxen molecule look like?

Two six-membered rings of carbon share one edge, giving a flat core of ten ring carbons. A methoxy group, an oxygen linking the ring to a methyl group, sits at one end; a propanoic acid arm ending in COOH sits at the other. The 3D model holds 31 atoms, fourteen each of carbon and hydrogen and three of oxygen, joined by 32 bonds.

Which enantiomer of naproxen works as a drug?

The S form, which HSDB names the effective isomer. It is the form PubChem's naproxen record holds, marked by the (2S) at the head of its IUPAC name, and the one the 3D model draws. HSDB also gives naproxen a specific optical rotation, the angle through which it turns polarised light, of +66° at 25 °C in chloroform.

How does naproxen sodium differ from naproxen?

Naproxen sodium is the sodium salt of naproxen(1−), the anion left when the acid loses its hydrogen. HSDB describes it as a white to creamy white powder that dissolves in water, where the acid barely dissolves. MeSH records both forms in treating rheumatoid arthritis and other joint and muscle disorders, period pain and acute gout.

Does naproxen carry a risk to the heart?

FDA's memorandum of 6 April 2005 followed a joint meeting of two of its advisory committees that February. It found that the trial data gave no assurance that naproxen adds no cardiovascular risk, and it could not rank the drug equal to or better than a placebo. ADAPT was the one long-term controlled trial setting naproxen and a COX-2 selective drug, one aimed at COX-2 alone, against a placebo.

Made of the same elements

C₁₅H₁₆O₂ Bisphenol A 33 atoms, 34 bonds.
C₁₃H₁₈O₂ Ibuprofen 33 atoms, 33 bonds.
C₂₀H₁₄O₄ Phenolphthalein 38 atoms, 41 bonds.
C₉H₈O₄ Aspirin 21 atoms, 21 bonds.
C₁₀H₂₀O Menthol 31 atoms, 31 single bonds.
C₈H₈O₃ Methyl salicylate 19 atoms, 19 bonds.
C₈H₈O₃ Vanillin 19 atoms, 19 bonds.
C₆H₁₂O₆ Fructose 24 atoms, 24 single bonds.

All 51 compounds made of carbon, hydrogen and oxygen

C₆H₁₂O₆ Glucose 24 atoms, 24 single bonds.
C₁₈H₂₄O₂ Estradiol 44 atoms, 47 bonds.
C₇H₆O₃ Salicylic acid 16 atoms, 16 bonds.
C₄H₉OH 1-Butanol 15 atoms, 14 single bonds.
C₆H₅COOH Benzoic acid 15 atoms, 15 bonds.
C₂H₅OC₂H₅ Diethyl ether 15 atoms, 14 single bonds.
C₆H₈O₆ Ascorbic acid 20 atoms, 20 bonds.
C₆H₅CHO Benzaldehyde 14 atoms, 14 bonds.
C₃H₇COOH Butyric acid 14 atoms, 13 bonds.
CH₃COOC₂H₅ Ethyl acetate 14 atoms, 13 bonds.
C₃H₈O₃ Glycerol 14 atoms, 13 single bonds.
C₄H₈O Butanone 13 atoms, 12 bonds.
C₆H₈O₇ Citric acid 21 atoms, 20 bonds.
C₁₂H₂₂O₁₁ Lactose 45 atoms, 46 single bonds.
C₆H₅OH Phenol 13 atoms, 13 bonds.
C₃H₈O₂ Propylene glycol 13 atoms, 12 single bonds.
C₁₂H₂₂O₁₁ Sucrose 45 atoms, 46 single bonds.
C₃H₇OH 1-Propanol 12 atoms, 11 single bonds.
C₃H₈O Isopropyl alcohol 12 atoms, 11 single bonds.
C₃H₆O₃ Lactic acid 12 atoms, 11 bonds.
C₄H₆O₅ Malic acid 15 atoms, 14 bonds.
C₂H₅COOH Propionic acid 11 atoms, 10 bonds.
C₁₉H₂₈O₂ Testosterone 49 atoms, 52 bonds.
C₃H₆O Acetone 10 atoms, 9 bonds.
C₂H₆O₂ Ethylene glycol 10 atoms, 9 single bonds.
C₁₆H₃₂O₂ Palmitic acid 50 atoms, 49 bonds.
C₄H₆O₆ Tartaric acid 16 atoms, 15 bonds.
CH₃OCH₃ Dimethyl ether 9 atoms, 8 single bonds.
C₂H₅OH Ethanol 9 atoms, 8 single bonds.
C₂H₄O₃ Glycolic acid 9 atoms, 8 bonds.
CH₃COOH Acetic acid 8 atoms, 7 bonds.
CH₃CHO Acetaldehyde 7 atoms, 6 bonds.
C₂H₄O Ethylene oxide 7 atoms, 7 single bonds.
C₂₁H₃₀O₂ Progesterone 53 atoms, 56 bonds.
H₂CO₃ Carbonic acid 6 atoms, 5 bonds.
C₂₁H₃₀O₅ Cortisol 56 atoms, 59 bonds.
CH₃OH Methanol 6 atoms, 5 single bonds.
C₁₈H₃₄O₂ Oleic acid 54 atoms, 53 bonds.
H₂C₂O₄ Oxalic acid 8 atoms, 7 bonds.
HCOOH Formic acid 5 atoms, 4 bonds.
CH₂O Formaldehyde 4 atoms, 3 bonds.
C₂₇H₄₄O Cholecalciferol 72 atoms, 74 bonds.
C₂₇H₄₆O Cholesterol 74 atoms, 77 bonds.