ISOXICAM Synthesis, SAR, MCQ, Structure, Chemical Properties and Therapeutic Uses
Isoxicam
IUPAC nomenclature
4-hydroxy-2-methyl-N-(5-methyl-1,2-oxazol-3-yl)-1,1-dioxo-1λ6,2-benzothiazine-3-carboxamide
Classification
- NSAID
- Oxicames
Physiochemical Properties
S. NO. | PHYSICAL AND CHEMICAL PROPERTIES | |
1 | Molecular weight | 335.34 g/mol |
2 | Physical appearance | Solid |
3 | Melting point | N/A |
4 | Solubility | 33.9 ug/ml |
5 | Octanol/water partition coefficient | 2.83 (logP) |
6 | Presence of ring | Isoxazole, benzothiazine |
7 | Number of chiral centers | 1 |
Mechanism of Action
- Isoxicam reversibly inhibits cyclooxygenase enzyme which causes peripheral inhibition of prostaglandin synthesis.
- It also has the platelet inhibitory action.
Structure Activity Relationship
General SAR for Oxicams can be summarized as follows:
- Substitution on the nitrogen atom of the thiazine ring gives optimum activity.
- Substitution on the caboxamide with aryl group gives compounds with greater activity than when substituents are alkyl groups.
- N-heterocyclic compounds are more acidic than N-aryl carboxamides.
- Primary carboxamides are more potent than secondary carboxamides.
- m-substituted derivatives are more potent than p-substituted derivatives.
- Maximum activity is found with m-Cl substituent in the aryl series.
- Substitution on the carboxamide Nitrogen with heteroaryl group gives compound with seven fold greater anti-inflammatory activity than the aryl group substitution. [1]
Method of synthesis
i. Reaction of saccharine with sodium hydroxide to give a sodium salt.
ii. Sodium salt so produced is reacted with methyl chloroacetate to give saccharine-substituted acetic acid ethyl ester.
iii. The above formed product undergoes rearrangement on reaction with dimethylsulfoxide to produce 1,1-dioxide-3-methoxycarbonyl-3,4-dihydro-2-H-1,2-benzothiazin-4-one.
iv. Last undergoes methylation at the nitrogen atom using methyl iodide followed by reaction with 3-amino-5-mehylisoxazole to give Isoxicam. [2]
Therapeutic Uses
Isoxicam is used for:
- Treatment of pain and swelling due to rheumatoid arthritis
Side Effects
Side effects of isoxicam are:
- Nausea
- Upset stomach
- Dizziness
- Headache
- Hypertension
- Easy bleeding
- Painful swallowing
- Ringing in ears
- Mood changes
- Change in amount of urine
- Stiff neck
- Vision problem
- Swelling ankles
- Tiredness
- Weight gain
- Dark urine
- Vomiting
- Loss of appetite
- Pale skin
- Allergic reactions
MCQs
Q.1 What can be the correct IUPAC nomenclature of Isoxicam?
a) 4-hydroxy-2-methyl-N-(5-methyl-1,2-oxazol-3-yl)-1,1-dioxo-1λ6,2-benzothiazine-3-carboxamide
b) 4-hydroxy-2-methyl-N-(5-methyl-1,2-oxazol-3-yl)-1,1-dioxo-1λ6,2-benzothiazine-3-Carboxylic acid
c) N-(3-Ethoxyphenyl) benzothiazine-3-carboxamide
d) N-(4-Ethoxyphenyl) benzothiazine-3-carboxamide
Q.2 Which amongst the following statements is/are incorrect related to the SAR of phenacetin?
I. Primary carboxamides are more potent than secondary carboxamides.
II. m-substituted derivatives are less potent than p-substituted derivatives.
III. Minimum activity is found with m-Cl substituent in the aryl series.
IV. Substitution on the carboxamide Nitrogen with heteroaryl group gives compound with seven fold greater anti-inflammatory activity than the aryl group substitution.
a) I, II
b) I, III
c) I
d) II, III
Q.3 Starting materials required by for the synthesis of Isoxicam can be?
I. Saccharine
II. Sodium hydroxide
III. Sulfuric acid
IV. Atropin
a) I, II
b) III, IV
c) I, IV
d) II, II, IV
Q.4 Side effects of drug Isoxicam is/are?
a) Painful swallowing
b) Ringing in ears
c) Vision problems
d) All of the above
Q.5 Match the following drugs with the correct number of the chiral carbons they have in their structure:
i. Isoxicam | A. 4 |
ii. Tolmetin | B. 1 |
iii. Atazanavir | C. 2 |
iv. Thiopental | D. 0 |
a) i-A, ii-C, iii-D, iv-B
b) i-D, ii-A, iii-C, iv-B
c) i-D, ii-B, iii-A, iv-C
d) i-B, ii-D, iii-A, iv-C
Q.6 An example of drug from class NSAIDs?
a) Tropicamide
b) Isoxicam
c) Methamphetamine
d) All of the above
Q.7 The type of ring system found in Isoxicam?
a) Isoxazole
b) Benzothiazine
c) Both a) and b)
d) None of the above
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ANSWERS
1-a
2-d
3-a
4-d
5-d
6-b
7-c