PIROXICAM Synthesis, SAR, MCQ,Structure, Chemical Properties and Therapeutic Uses

Piroxicam

IUPAC nomenclature

4-hydroxy-2-methyl-1,1-dioxo-N-pyridin-2-yl-1λ6,2-benzothiazine-3-carboxamide

 

Classification

  • NSAID
  • Oxicames

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 331.3g/mol
2 Physical appearance Solid
3 Melting point 199°C
4 Solubility 23 mg/L
5 Octanol/water partition coefficient 3.06
6 Presence of ring Pyridine, thiazine
7 Number of chiral centers 1

 

Mechanism of Action

  • Piroxicam reversibly inhibits cyclooxygenase enzyme which causes peripheral inhibition of prostaglandin synthesis.
  • Piroxicam also prevents the aggregation due to platelets through inhibiting the migration of the leukocytes into the site of inflammation which prevents the formation of thromboxane A2.

 

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 2-aminopyridine to give piroxicam. [2]

Therapeutic Uses

Piroxicam is used for:

  • Treatment of pain and swelling due to rheumatoid arthritis 

 

Side Effects

Side effects of piroxicam 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 “4-hydroxy-2-methyl-1,1-dioxo-N-pyridin-2-yl-1λ6,2-benzothiazine-3-carboxamide” is the IUPAC nomenclature of which drug?

a) Piroxicam

b) Epinephrine

c) 6-fluorouracil

d) Oxymetazoline

Q.2 Melting point of piroxicam is?

a) 199oC

b) 981K

c) 273K

d) None of the above

Q.3 Match the following with correct classifications of the drugs.

i. Piroxicam A. Non-selective adrenergic agonist
ii. Epinephrine B.ß1-adrenergic agonist
iii. Dopamine C. α1-adrenergic agonist
iv. Methyldopa D. NSAID

 a) i-A, ii-D, iii-B, iv-C

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

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

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

Q.4 Correct statements from below which are related with the mechanism of action of piroxicam can be??

I. It irreversibly inhibits COX

II. It prevents aggregation of platelets

III. There is increase in the amount of prostaglandins due to the drug.

IV. Piroxicam also inhibits the migration of leukocytes at the site of inflammation.

a) II ,IV

b) III, II

c) IV , I

d) II , III

Q.5   Correct sequence for True and False for the given statements related with the SAR of oxicams can be?

  • 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.

a) TFFT

b) FFTT

c) FTFT

d) TTTT

Q.6  Type of ring present in the structure of piroxicam?

a) Pyridine

b) Thiazine

c) Anthracene

d) Both a) and b) 

Q.7 The drug piroxicam is mainly used for?

a) Treatment of seizures

b) As an anesthetic

c) Reducing pain due to arthritis

d) All of the above

 

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ANSWERS

1-a

2-a

3-b

4-a

5-d

6-d

7-c

 

REFERENCES

[1]  Lemke TL, Williams DA, Roche VF, Zito SW. FOYE. S Principles of Medicinal Chemistry. Seventh Edition Copyright. 2013.

[2] Vardanyan R, Hruby V. Synthesis of essential drugs. Elsevier; 2006 Mar 10.

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