Diclofenac chemical structure (NSAID), 2D skeletal formula, C14H11Cl2NO2

Diclofenac Chemical Structure

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1. Identification

Summary

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) used for relief of pain, fever, and inflammation across oral, injectable, topical, ophthalmic, and rectal routes; like other NSAIDs, labeling warns about serious cardiovascular and gastrointestinal risks with systemic use.

Brand Names

Voltaren, Cataflam, Cambia, Zipsor, Zorvolex (regional/generic variants common)

Name

Diclofenac

Background

A benzeneacetic acid–class NSAID introduced in the 1970s; supplied as free acid and multiple salts (e.g., sodium, potassium, diethylamine, epolamine) formulated for systemic or topical delivery.

Modality

Small molecule

Groups

Approved; OTC/Rx (region-dependent)

Structure

Diclofenac 2D chemical structure (benzeneacetic acid derivative). Formula C14H11Cl2NO2; IUPAC [2-(2,6-dichloroanilino)phenyl]acetic acid; CAS 15307-86-5.
Diclofenac chemical structure (NSAID), 2D skeletal formula, C14H11Cl2NO2

Weight

~296.15 g/mol (free acid)

Chemical Formula

C₁₄H₁₁Cl₂NO₂ (free acid)

Synonyms

2-[2-(2,6-dichloroanilino)phenyl]acetic acid; diclofenac free acid

External IDs

CAS (free acid): 15307-86-5; PubChem CID: 3033
UNII (active moiety): 144O8QL0L1; ATC (oral/parenteral/rectal): M01AB05

2. Pharmacology

Indication

Short-term treatment of mild–moderate pain; symptomatic relief in osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, primary dysmenorrhoea; acute migraine (certain oral products); postoperative/ocular inflammation (ophthalmic/topical forms).

Associated Conditions

Musculoskeletal pain, tendonitis/bursitis, dental/post-traumatic pain; actinic keratosis or localized OA (topical forms per label).

Associated Therapies

Co-use with gastroprotection (e.g., PPI) in high GI-risk patients; fixed-dose diclofenac/misoprostol in some markets.

Contraindications & Blackbox Warnings

NSAID boxed warnings for CV thrombotic events and GI bleeding/ulcer/perforation; contraindicated for CABG peri-operative pain, in NSAID/aspirin hypersensitivity, and from 30 weeks’ gestation due to fetal ductus arteriosus risk.

Pharmacodynamics

Reversible COX-1/COX-2 inhibition reduces prostaglandins → analgesic, antipyretic, anti-inflammatory effects; high protein binding and tissue distribution contribute to effect persistence beyond plasma half-life.

Mechanism of action

Competitive inhibition of prostaglandin-endoperoxide synthases (COX-1/COX-2), lowering PGE₂/TXA₂ synthesis; some COX-2 preference reported in vitro; clinical selectivity remains dose-/context-dependent.

Absorption

Oral bioavailability is limited by first-pass metabolism; salts/formulations (e.g., potassium, enteric-coated sodium, soft-gel) alter tₘₐₓ and tolerability; topical forms produce lower systemic exposure.

Volume of distribution

Typically ~0.1–0.2 L/kg (low to moderate), with penetration into synovial fluid reported.

Protein binding

>99% (primarily albumin)

Metabolism

Extensive hepatic metabolism: oxidative CYP2C9 (and others) to hydroxylated metabolites plus UGT2B7 glucuronidation; metabolites generally inactive.

Route of elimination

Predominantly as metabolites via urine (major) and bile/feces (minor to moderate); little unchanged drug renally excreted.

Half-life

Unchanged diclofenac ~1–2 h (longer for total metabolites/apparent effect).

Clearance

Apparent oral clearance influenced by formulation, hepatic function, and drug interactions (e.g., CYP2C9 modulators).

Adverse Effects

Dyspepsia, nausea, abdominal pain, edema, dizziness, rash; serious events include GI bleeding, CV thrombotic events, hepatic injury, renal events, anaphylaxis, and severe cutaneous reactions.

Toxicity

Overdose typically managed supportively; chronic/high-dose risks align with class warnings; topical misuse still carries systemic risk.

Pathways

COX inhibition → ↓prostaglandins; distribution into inflamed tissues; enterohepatic handling varies by product.

Pharmacogenomic Effects/ADRs

CYP2C9 genotype and inhibitors can alter exposure; routine PGx testing not standard—monitor when interacting drugs/diseases present.

3. Interactions

Drug Interactions

  • Anticoagulants/antiplatelets/SSRIs/SNRIs: ↑ bleeding risk.
  • ACEI/ARB/diuretics (“triple whammy”): additive renal risk.
  • CYP2C9 inhibitors/inducers (e.g., fluconazole / rifampin): ↑/↓ diclofenac exposure.
  • Other NSAIDs/salicylates: avoid co-use (↑ toxicity, little added benefit).
  • Lithium/methotrexate: potential ↑ levels—monitor.

Food Interactions

Food/enteric coating can delay tₘₐₓ and improve GI tolerability; alcohol co-use increases GI risk.

4. Categories

ATC Codes

M01AB05 (systemic); topical and ophthalmic subclasses exist (e.g., M02AA15, S01BC03 per product).

Drug Categories

NSAID; Analgesic; Antipyretic; Anti-inflammatory; Small molecule

Chemical Taxonomy

Aromatic benzeneacetic acid derivative; diphenylamine motif with 2,6-dichloro substitution

Affected organisms

Humans (therapeutic use)

5. Chemical Identifiers

UNII

144O8QL0L1 (diclofenac, active moiety)

CAS number

15307-86-5 (diclofenac free acid)

InChI Key

DCOPUUMXTXDBNB-UHFFFAOYSA-N

InChI

InChI=1S/C14H11Cl2NO2/c15-10-5-3-6-11(16)14(10)17-12-7-2-1-4-9(12)8-13(18)19/h1-7,17H,8H2,(H,18,19)

IUPAC Name

[2-(2,6-dichloroanilino)phenyl]acetic acid

SMILES

O=C(O)Cc1ccccc1Nc2c(Cl)cccc2Cl

6. References

  1. PubChem Compound Summary: Diclofenac (CID 3033) — formula C₁₄H₁₁Cl₂NO₂, identifiers, structure. PubChem
  2. FDA GSRS / UNII — Diclofenac active moiety UNII 144O8QL0L1, InChIKey DCOPUUMXTXDBNB-UHFFFAOYSA-N. precisionFDA
  3. ATC/DDD Index (FHI) — systemic M01AB05 diclofenac; route/DDDs. atcddd.fhi.no
  4. NIST WebBook — InChI / molecular formula / MW confirmation for diclofenac free acid. NIST WebBook
  5. DailyMed / FDA labels — NSAID boxed warnings; GI/CV risks; pregnancy (≥30 wks) ductus risk. DailyMed
  6. Drugs.com Pro (label compendium) — PK summary (half-life ~2 h), elimination primarily via metabolism. Drugs.com
  7. DrugBank — Vd/clearance ranges; metabolizing enzymes (CYP2C9; UGT2B7). DrugBank
  8. Peer-reviewed PK sources — High protein binding (>99%), Vd ~0.12–0.17 L/kg, first-pass effect. PTFarm+1

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