Bromfenac sodium

Description

Bromfenac Sodium was launched in the US as a potent, orally-active, long lasting peripheral analgesic with antiinflammatory properties. It is structurally similar to ketoprofen and diclofenac and can be prepared in three steps from 2-amino-4’-bromophenone using Gassman’s oxindole synthesis. Duract’s biological effects are a result of its ability to reduce prostaglandin production through inhibition of cyclooxygenase. As a 4-bromo derivative of Amfenac, this modification increased the duration of analgesic activity and antiinflammatory potency. It was also free of any CNS, cardiovascular or autonomic effects. In comparison, 5 mg of Duract was equipotent to 650 mg of ASA and 25 mg was slightly more potent than 400 mg of Ibuprofen.

Description

Bromfenac is an inhibitor of cyclooxygenase 2 (COX-2; IC₅₀ = 6.6 nM) that is selective over COX-1 (IC₅₀ = 210 nM). It inhibits prostaglandin E₂ (PGE₂; ) production in a rabbit model of LPS-induced eye inflammation. Bromfenac also decreases inflammation following cataract removal in dogs when administered as a 0.9% topical solution on a tapering schedule for 24 weeks. Formulations containing bromfenac have been used in the treatment of postoperative inflammation following cataract surgery.

Originator

American Home Products (US)

Uses

Bromfenac (Xibrom, ISTA Pharmaceuticals, Irvine, USA; Bronuck, Senju Pharmaceutical, Osaka, Japan) is indicated for the treatment of postoperative inflammation and the reduction of ocular pain in patients after undergoing cataract extraction. For this task, one drop of Xibrom may be applied to the affected eye twice daily beginning 24 hours after cataract surgery and continuing for the first 2 weeks of the postoperative period. The clinical safety and efficacy of bromfenac have been extensively studied in diverse comparative investigations, including the treatment of external or anterior ocular inflammatory diseases, allergic conjunctivitis, scleritis, and postoperative inflammation.The results of two phase III multicenter, randomized double-masked placebo-controlled clinical trials showed that bromfenac ophthalmic solution 0.09% was effective in the rapid resolution of ocular pain after cataract surgery, and there was a statistically significant difference between the bromfenac and placebo groups demonstrated in these phase III clinical trials.

Uses

Bromfenac sodium has been used:

• to study its ability to bind to melanin
• in the synthesis of bromfenac indolinone standard
• to analyze its permeability in porcine conjunctiva

Definition

ChEBI: The sodium salt of bromfenac. Note that 'bromfenac sodium' commonly refers to the sesquihydrate (120638-55-3); this is the anhydrous form.

Manufacturing Process

Reaction of (2-aminophenyl)-(4-bromophenyl)-methanone with methylsulfanylacetic acid ethyl ester and tert-butyl hypochlorite gives a corresponding sulfonium salt. This salt was transformed to initially to the betaine. Electrocyclic rearrangement of that transient intermediate leads, after rearomatization, to the homoanthranilic acid. Internal ester-amine interchange leads then to 4-bromophenyl-(3-(methylthio)indolin-7-yl)methanone. The thiomethyl group is then removed with Raney nickel to give 4-bromophenyl- (indolin-7-yl)methanone. Saponification of this intermediate affords the (2- amino-3-(4-bromobenzoyl)-phenyl)-acetic acid (Bromfenac).
In practice it is usually used as sodium salt.

brand name

Duract

Therapeutic Function

Analgesicá Antiinflammatory

Biochem/physiol Actions

Bromfenac exhibits antipyretic and prostaglandin synthetase inhibiting properties. It has therapeutic properties against the reduction of ocular pain and inflammation in postoperative cataract patients. Bromfenac acts as an effective agent against allergic conjunctivitis. It has the potential to treat acute muscle pain, osteoarthritis, and rheumatoid arthritis.

References

[1] Patent: CN108569975, 2018, A. Location in patent: Paragraph 0034; 0039; 0040
[2] Journal of Medicinal Chemistry, 1984, vol. 27, # 11, p. 1379 - 1388
[3] Patent: CN104974057, 2018, B. Location in patent: Paragraph 0056-0061