a brief notes related to non steroidal anti inflammatory drugs

1. Medicinal Chemistry 2016
1 | R a o ' s c o l l e g e o f p h a r m a c y , N e l l o r e .
Non-SteroidalAnti Inflammatory Drugs (NSAIDS)
Introduction:
The non-steroidal anti inflammatory drugs are widely used for the treatment of minor
pain and for the management of edema and tissue damage resulting from inflammatory joint
disease.
A number of these drugs possess antipyretic activity in addition to having analgesic
and anti-inflammatory action and thus have utility in the treatment of fever.
Some of the primary indications for NSAID therapy include: Rheumatoid arthritis,
osteoarthritis, acute gouty arthritis, ankylosing spondylitis, dysmenorrhea, and tissue damage
resulting from inflammatory joint disease.
Mechanismof action:
The major mechanism by which the NSAIDs elicit their therapeutic effects
(antipyretic, analgesic, and anti inflammatory activities) is inhibition of prostaglandin
synthesis. Specifically NSAIDs competitively inhibit cyclooxygenases (Prostaglandin
synthetase), the enzymes that catalyze the synthesis of cyclic endoperoxides from arachidonic
acid to form prostaglandins.
Generally, the NSAIDs inhibit both COX-1 and COX-2. Most NSAIDs are mainly
COX-1 selective (e.g., aspirin, ketoprofen, indomethacin, sulindac). Others are considered
slighty selective for COX-1 (e.g., ibuprofen, naproxen, diclofenac) and others may be
considered slightly selective for COX-2 .
Classification:
NSAIDs may be classified on the basis of their basic chemical structures as described below
along with various classical examples belonging to each category, namely :
1. Heteroarylacetic acid analogues 2. Aryl acetic acid analogues
3. Aryl propionic acid analogues 4. Naphthalene acetic acid analogues
5. Gold compounds 6. Salicylic acid analogues and
7. Pyrazolones and pyrazolodiones
1. Heteroarylacetic acidanalogues:
This constitutes an important class of non-steroidal anti-inflammatory drugs which have
gained recognition in the recent past. A few classical examples of this group are,
indomethacin, sulindac.
Indomethacin:

2. Medicinal Chemistry 2016
2 | R a o ' s c o l l e g e o f p h a r m a c y , N e l l o r e .
MOA:
The ‘drug’ exerts its pharmacologic activity by inhibiting the enzyme cyclo-oxygenase
Besides, it has been proved beyond any reasonable doubt that the ‘drug’ also inhibits the
synthesis of useful prostaglandins both in the GI-tract and kidney.
Uses:
It is usually used for the treatment of rheumatoid arthritis, ankylosing (rheumatoid)
spondylitis, gouty arthritis and osteoarthritis.
Sulindac:
MOA:
The precise mechanism of action of the ‘drug’ is still unknown. However, it is believed that
the ‘sulphide metabolite’ may perhaps inhibit the prostaglandin synthesis
Uses:
It is usually employed in the treatment of rheumatic and musculoskeletal disorders.
2. Arylacetic acid analogues:
A few potent analogues belonging to this class of compounds are described below :
ibuprofen ; diclofenac sodium
Ibuprofen:
Uses:
It is indicated for the treatment of rheumatoid arthritis and osteoarthritis. It is also
recommended to arrest acute flares and in the long-term management of these diseases.

3. Medicinal Chemistry 2016
3 | R a o ' s c o l l e g e o f p h a r m a c y , N e l l o r e .
Diclofenac sodium:
MOA:
The ‘drug’ is believed to exert a wide spectrum of its effects as a consequence of its ability to
inhibit the prostaglandin synthesis noticeably
Uses:
It is mostly employed in the treatment of rheumatoid arthritis and rheumatic disorders.
3. Arylpropionic acid analogues:
Like the arylacetic acids the arylpropionic acid analogues also exhibit potent anti-
inflammatory properties besides usual antipyretic and analgesic characteristics. A few
examples of this category of compounds are discussed here, flurbiprofen ; ketoprofen.
Flurbiprofen:
Uses:
It is generally employed in the treatment of rheumatoid arthritis and other rheumatic
disorders.
Ketoprofen:
Uses:
It is used in the treatment of rheumatoid arthritis and osteoarthritis.
4. Naphthalene acetic acidanalogues:
Example : Naproxen.

4. Medicinal Chemistry 2016
4 | R a o ' s c o l l e g e o f p h a r m a c y , N e l l o r e .
Naproxen:
MOA:
It reversibly inhibits both COX-1 and COX-2 enzymes.
Uses:
It is commonly used for the reduction of rheumatoid arthritis, osteo arthritis, migraine.
5.Goldcompounds:
In general, gold compounds either suppress or prevent, but do not cure arthritis and synovitis.
A few classical examples of this class of compounds are discussed below. Examples:
aurothioglucose ; aurothioglucanide
Aurothioglucose:
Uses:
It is an antirheumatic drug employed for treatment of active and progressing arthritis. It has
been reported that no other antirheumatic drug possesses the capability of arresting the
progression of the disease, as gold can do in some cases.
6. Salicylic acid analogues:
A good number of salicylic acid analogues have also been found to possess anti-
inflammatory actions, e.g., aspirin, sodium salicylate, salicylamide etc., in addition to their
antipyretic analgesic property.

5. Medicinal Chemistry 2016
5 | R a o ' s c o l l e g e o f p h a r m a c y , N e l l o r e .
Sodium salicylate:
Uses:
It is employed in rheumatic fever and symptomatic treatment of gout.
Salicylamide:
Aspirin:
SAR:
 Transformation of the carboxylic acid group into the corresponding amide, maintains
the analgesic activity but not the anti-inflammatory activity.
 Placing the phenolic hydroxyl group in meta or para positions, abolishes the activity.
 Substitution of halogens on the aromatic ring at the 5-position of salicylic acid
increases anti-inflammatory activity.
7.Pyrazolonesand pyrazolodiones
Drugs like phenazone, phenylbutazone, oxyphenbutazone etc., belonging to this category,
besides their antipyretic-analgesic action, have also been reported to exhibit anti-
inflammatory properties.

6. Medicinal Chemistry 2016
6 | R a o ' s c o l l e g e o f p h a r m a c y , N e l l o r e .
Phenylbutazone:
Oxyphenbutazone:
Phenazone:
SAR:
 The dicarbonyl functions at 3- and 5- positions enhance the acidity of the
hydrogen at 4-position.
 Eliminating the acidic proton at the 4-position abolishes anti-inflammatory
activity.
 Enhancing the acidity too much leads to a decrease in anti-inflammatory
activity.