6-Methoxy naphthalene acetic acid

• CAS: 23981-47-7
• Catalog Number: ACM23981477
• Category: Main Products
• Molecular Weight: 216.23
• Molecular Formula: C₁₃H₁₂O₃
• Appearance: off-white solid

Case Study

Enhancing Topical Delivery of 6-Methoxy-2-Naphthylacetic Acid through Strategic Salt Formation

Pawar, Vijay, et al. Drug Delivery 22.3 (2015): 359-366.

6-Methoxy-2-naphthylacetic acid (6-MNA), the active metabolite of the anti-inflammatory prodrug nabumetone, possesses a favorable pharmacokinetic profile including a long half-life. To optimize its delivery for potential topical or transdermal applications, this study investigated the strategy of forming pharmaceutically acceptable salts of 6-MNA to enhance its solubility and percutaneous flux.
Salt Synthesis: 6-MNA was dissolved in dichloromethane (with small amounts of methanol as needed) and reacted with an equimolar amount of base. After stirring 6-8 hours, the precipitated salts were collected and purified by recrystallization from ethyl acetate. Salt forms prepared included salts with ethanolamine, diethanolamine, triethanolamine, diethylamine, and sodium.
Key Results:
· DSC thermograms and FT-IR spectra indicated ionic association between 6-MNA and the tested organic/alkali bases. Amino-based salts (ethanolamine, diethanolamine, triethanolamine, diethylamine) displayed lower melting points than the free acid, while the sodium salt had a higher melting point than 6-MNA.
· All salt forms showed increased aqueous solubility relative to the parent acid in phosphate buffers at pH 5.0 and 7.4. At pH 5.0, log P values for salts were similar to the free acid; at pH 7.4 the salts' log P values increased by 4-10 fold versus 6-MNA.
· Enhanced permeation: Each salt improved skin flux compared with 6-MNA. Notably, the ethanolamine salt exhibited the largest enhancement - 7.7-fold greater permeability at pH 5.0 and 9.4-fold greater at pH 7.4 relative to the free acid.

Investigating the Polymorphic Metabolism of 6-Methoxy-2-Naphthylacetic Acid (6-MNA) by CYP2C9 Enzymes

Matsumoto, Kaori, et al. Journal of Pharmaceutical Investigation 50.1 (2020): 71-79.

This investigation evaluated how human cytochrome P450 CYP2C9 and two common genetic variants (CYP2C9*2 and CYP2C9*3) metabolize 6-methoxy-2-naphthylacetic acid (6-MNA) and whether 6-MNA interacts with CYP2C9-mediated metabolism of a clinically important substrate (S-warfarin).
Analysis Method: 6-MNA was utilized as the substrate to study its specific oxidative metabolism via O-demethylation to form 6-hydroxy-2-naphthylacetic acid (6-HNA). The investigation employed two primary systems: recombinant human CYP2C9 enzymes (the wild-type CYP2C9.1 and the variant forms CYP2C9.2 and CYP2C9.3) and human liver microsomes genotyped for these CYP2C9 alleles.
Key Findings:
· Variant-Specific Metabolic Activity: The intrinsic clearance (Vmax/Km) for the formation of 6-HNA was significantly reduced-by approximately two-thirds-using the recombinant CYP2C9.3 variant compared to the wild-type CYP2C9.1. The CYP2C9.2 variant showed activity similar to the wild-type.
· Confirmation in Human Liver Microsomes: Analysis using genotyped human liver microsomes corroborated the recombinant enzyme findings. Microsomes homozygous for the CYP2C93 allele (3/*3) showed a 4 to 6-fold lower intrinsic clearance for 6-HNA formation compared to those with the wild-type genotype (*1/*1).
· Potential for Drug-Drug Interaction: 6-MNA exhibited a mixed-type inhibition of S-warfarin 7-hydroxylation by CYP2C9. The inhibitory constant (Ki) was higher for the CYP2C9.3 variant than for CYP2C9.1, indicating a difference in interaction strength.

Custom Q&A

What is the molecular formula of 6-Methoxy naphthalene acetic acid?

The molecular formula is C13H12O3.

What are the synonyms for 6-Methoxy naphthalene acetic acid?

Some synonyms include 2-(6-methoxynaphthalen-2-yl)acetic acid, 6-Methoxy-2-naphthylacetic acid, and alpha-Demethylnaproxen.

What is the chemical structure of 6-Methoxy naphthalene acetic acid?

The chemical structure can be seen in the provided 2D and 3D images.

Is 6-Methoxy naphthalene acetic acid considered an irritant?

Yes, it is considered an irritant.

What is the IUPAC name of 6-Methoxy naphthalene acetic acid?

The IUPAC name is 2-(6-methoxynaphthalen-2-yl)acetic acid.

What is the InChIKey of 6-Methoxy naphthalene acetic acid?

The InChIKey is PHJFLPMVEFKEPL-UHFFFAOYSA-N.

Is 6-Methoxy naphthalene acetic acid a drug metabolite?

Yes, it is a drug metabolite.

What is the CAS number of 6-Methoxy naphthalene acetic acid?

The CAS number is 23981-47-7.

What is the European Community (EC) number of 6-Methoxy naphthalene acetic acid?

The EC number is 245-967-1.

What is the canonical SMILES of 6-Methoxy naphthalene acetic acid?

The canonical SMILES is COC1=CC2=C(C=C1)C=C(C=C2)CC(=O)O.

Synthetic Use

Upstream Synthesis Route 1

• 54828-56-7

• 23981-47-7

Reference: [1] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 9, p. 759 - 763
[2] ACS Chemical Biology, 2017, vol. 12, # 9, p. 2379 - 2387

Upstream Synthesis Route 2

• 53077-21-7

• 23981-47-7

Reference: [1] Tetrahedron Letters, 2009, vol. 50, # 31, p. 4541 - 4544
[2] Archiv der Pharmazie, 2007, vol. 340, # 2, p. 88 - 94

Upstream Synthesis Route 3

• 23981-48-8

• 23981-47-7

Reference: [1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2004, vol. 43, # 6, p. 1292 - 1298

Upstream Synthesis Route 4

• 10441-46-0
• 77-78-1

• 23981-47-7

Reference: [1]Bulletin de la Societe Chimique de France,1955,p. 962,965

Upstream Synthesis Route 5

• 3900-45-6

• 23981-47-7

Reference: [1]Synthetic Communications,1991,vol. 21,p. 1353 - 1360
[2]Bulletin de la Societe Chimique de France,1955,p. 962,965
[3]Journal of labelled compounds and radiopharmaceuticals,2008,vol. 51,p. 239 - 241

Downstream Synthesis Route 1

• 23981-47-7
• 7803-49-8

• 125542-34-9

Reference: [1]Journal of Medicinal Chemistry,1990,vol. 33,p. 992 - 998

* For details of the synthesis route, please refer to the original source to ensure accuracy.