Nabumetone

Inquiry

Cat Number

API0231535

CAS Number

42924-53-8

If you have any other questions, please contact our experts.

Product Detail Description Scientific Support Customer Q&A

CAS Number

42924-53-8

EINECS

641-917-1

Storage

Store at room temperature

Synonyms

Relafen; 4-(6-methoxynaphthalen-2-yl)butan-2-one; Nabumetona; Nabumetonum; BRL-14777

Molecular Formula

C15H16O2

Molecular Weight

228.29

Smiles

CC(=O)CCC1=CC2=C(C=C1)C=C(C=C2)OC

Appearance

White to off-white crystalline powder

Melting Point

80-81℃

Boiling Point

371.1℃

Relative Density

1.084

General Description

Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) of the naphthylalkanone class, administered as a prodrug that is activated following hepatic metabolism. It is available in oral tablets and is characterized by its neutral gastrointestinal tolerability profile relative to other NSAIDs. The drug is a weak inhibitor of cyclooxygenase itself but undergoes rapid first-pass conversion to its active metabolite.

Mechanism of Action

Nabumetone is rapidly absorbed and undergoes extensive hepatic reduction to its active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA). This metabolite selectively inhibits cyclooxygenase-2 (COX-2) with approximately threefold greater potency than COX-1, though it is not considered a true selective COX-2 inhibitor. The preferential COX-2 inhibition contributes to its anti-inflammatory and analgesic effects while potentially reducing the risk of gastric mucosal injury associated with non-selective agents.

Application

It is indicated for the management of osteoarthritis and rheumatoid arthritis, providing relief of signs and symptoms including pain, swelling, and morning stiffness. The once- or twice-daily dosing schedule offers a convenience advantage over many other NSAIDs. While associated with a lower incidence of endoscopic ulcers compared to non-selective NSAIDs, it still carries warnings regarding cardiovascular risk, gastrointestinal bleeding, and renal impairment, as with all NSAIDs.

This mechanistic study elucidates how CYP1A2 converts the prodrug nabumetone to its active anti‑inflammatory metabolite, 6‑methoxy‑2‑naphthylacetic acid (6‑MNA). Using authentic synthetic standards, the authors demonstrate a three‑step pathway: 3‑hydroxylation, carbon‑carbon cleavage to an aldehyde, and oxidation of the aldehyde to the acid. All steps are catalyzed by CYP1A2, with other P450 enzymes being less effective. Importantly, the carbon‑carbon bond cleavage is mediated by the ferric peroxo anion rather than the ferryl species typical of most P450 reactions. CYP1A2 also catalyzes O‑demethylation and alcohol‑to‑ketone transformations of nabumetone and its analogs, revealing a versatile enzymatic capability.

Fig. 1 Schematic outline of the synthesis of nabumetone derivatives (2–11) from nabumetone. (Varfaj F, et al., 2014)

References

Varfaj F, et al. Carbon-carbon bond cleavage in activation of the prodrug nabumetone. Drug Metab Dispos. 2014; 42(5):828-838.

Does Nabumetone require protection from light during long-term storage?

Yes, it is photosensitive. Prolonged exposure to UV light can cause discoloration and degradation. Store in light-resistant containers in a cool, dry place.

What is the recommended storage temperature for Nabumetone?

Store at controlled room temperature (15-25°C). Avoid excessive heat above 30°C, which can soften the material and accelerate oxidative degradation.

Is Nabumetone stable in tablet formulations with standard excipients?

Yes, it shows good stability. We provide compatibility data for common fillers, binders, and disintegrants, with recommended moisture-protective packaging.

How is the impurity 6-methoxy-2-naphthylacetic acid monitored?

This active metabolite is also a potential degradation product. We use a validated HPLC method to control its levels in the API during storage.