Nabumetone

IUPAC nomenclature

4-(6-methoxy-2-naphthyl)-2-butanone

Classification

• NSAID
• Nonacidic prodrug

Physiochemical Properties

Mechanism of Action

• Nabumetone converts into its active metabolite 6-MNA which inhibits COX-1 and COX-2 with greater selectivity for COX-2 enzyme.
• This results in reduction of the conversion of the arachidonic acid to prostaglandins and thromboxane.

Structure Activity Relationship

SAR of  class Pyranocarboxylic acid can be summarized as follows:

• Introduction of methyl or ethylgroups on the butanone side chain decreases the anti-inflammatory activity of drug.
• Conversion of ketone group into dioxolane retains the activity.
• Conversion of ketone into oxime group decreases the activity
• Activity is reduced on removing the methoxy group from the 6^th-position.
• Replacement of the methoxy group at 6^th position with methyl or chloro group retains the activity.
• Replacement of methoxy group at 6^th-position with acetoxy, hydroxyl, N-methylcarbamoyl groups decreases the activity.[1]

Method of synthesis

i. 2-acetyl-5-bromo-6-methoxynaphthalene is reacted with alkyl acetate in presence of alkaline alcoholate to get 4-(5-bromo-6-methoxy-2-naphthyl)-4-hydroxybut-3-en-2-one.

ii. Last undergoes catalytic hydrogenation with hydrogen at 1-10 atm pressure.

iii. The product is filtered and concentrated under vacuum condition to get the oily substance.

iv. The oily substance undergoes crystallization by alcohols and forms bisulfitic complex with sodium bisulfate in polar solvents.

v. The bisulfitic complex is treated with aqueous solution of hydroxide, carbonate or bicarbonate of an alkali metal to restore nabumetone.[2]

Therapeutic Uses

Nabumetone is used for:

• Treatment of osteoarthritis
• Treatment of rheumatoid arthritis

Side Effects

Side effects of nabumetone are:

• Allergic reactions
• Skin reactions
• Increasing the risk of fatal heart attack or stroke
• Chest pain
• Numbness
• Weakness
• Shortness of breath
• Swelling of legs
• Slurred speech
• Vision changes
• Rapid weight gain
• Stomach bleeding
• Nausea
• Loss of appetite
• Jaundice
• Pale skin
• No urination
• Anemia
• Nausea
• Vomiting
• Indigestion
• Diarrhea
• Constipation
• Dizziness
• Headache
• Tiredness
• Ringing sounds in ears

MCQs

Q.1 Mechanism of action of nabumetone is due to?

a) Inhibition of COX enzyme

b) Inhibition of Acetylcholinestrase

c) Alkylation of the genetic material

d) Stimulating α-adrenoceptors

Q.2 Therapeutic use of drug nabumetone is/are?

a) Treatment of oesteoarthritis

b) Treatment of malignant tumors

c) As an anesthetic agent

d) All of the above

Q.3 Which amongst the following are the correct statements with respect to the SAR of class Pyranocarboxylic acids?

I. Introduction of methyl or ethylgroups on the butanone side chain decreases the anti-inflammatory activity of drug.

II. Conversion of ketone group into dioxolane retains the activity.

III. Conversion of ketone into oxime group decreases the activity

IV. Activity is reduced on removing the methoxy group from the 6^th-position.

a) I, II, III, IV

b) II, IV

c) I, III, IV

d) II, III

Q.4 Number of chiral carbons present in the structure of nabumetone is?

a) 0

b) 1

c) 2

d) 3

Q.5 Correct sequence for the True/False for the physiochemical properties of the drug Nabumetone?

• Molecular weight:228.29 gm/mol
• Physical appearance: Solid
•  Melting point: 78-82⁰C
• Octanol/water partition coefficient: 3.1

a) TFFT

b) FFTF

c) TTTT

d) FFFF

Q.6 Correct statements for the IUPAC nomenclatures of the drugs are?

I. Nabumetone: 4-(6-methoxy-2-naphthyl)-2-butanone

II. Cisplatin: (SP-4-2)-diamminedichloroplatinum(II)

III. Mitoxantron: 1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]-anthracene-9,10-dione.

IV. 6-Thioguanine: 2-amino-1H-purine-6(7H)-thione

a) I, III

b) II, III, IV

c) I, IV

d) I, II, III, IV 

Q.7 Match the following drugs with their correct classifications-

 a) i-A, ii-D, iii-B, iv-C

b) i-B, ii-A, iii-D, iv-C

c) i-B, ii-C, iii-A, iv-D

d) i-A, ii-B, iii-C, iv-D

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ANSWERS

1-a

2-a

3-a

4-a

5-c

6-d

7-b

REFERENCES