BRAINWARE UNIVERSITY

[BP402T] CLASS NOTES [Medicinal Chemistry-I]

NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used primarily to treat inflammation, mild-
to-moderate pain, and fever. Specific uses include the treatment of headache, arthritis, sports
injuries, and menstrual cramps.
Aspirin is used to inhibit the clotting of blood and prevent strokes and heart attacks in
individuals at high risk. NSAIDs are also included in many cold and allergic preparations.
Mode of action: NSAIDs inhibit cycloxygenase (COX), the enzyme that catalyses the synthesis
of cyclic endoperoxides, from the arachidonic acid to form PGs. The two COX isoenzymes are
COX-1 and COX-2. The function of COX-1 is to produce PGs that are involved in normal
cellular activity, (protection of gastric mucosa, maintenance of kidney function). While, COX-2
is responsible for the production of PGs at the inflammation sites. Most NSAIDs inhibit both
COX-1 and COX-2 with varying degree of selectivity. Selective COX-2 inhibitor may eliminate
the side effects associated with NSAIDs due to COX-1 inhibition, such as gastric and renal
effect.

Fig: MOA of NSAIDS

Side effects
In stomach: Biosynthesis of PGs, especially PGE2 and PGI2, serves as cytoprotective agents in
gastric mucosa; these PGs inhibit acid secretion by the stomach, enhance mucosal blood fl ow,
and promote the secretion of cytoprotective mucus in the GIT. Inhibition of the PGs synthesis
may make the stomach more susceptible to damage and lead to gastric ulcer.
In platelets: Platelet’s function gets disturbed because NSAIDs prevent the formation of
Thromboxane A (TXA2) in platelets, as TXA is a potent platelet-aggregating agent. This
accounts for the tendency of these drugs to increase the bleeding time and this side effect has
been exploited in the prophylactic treatment of thromboembolic disorder.

2021-22 Prepared by: Mr. Arnab Seth (Brainware University, Barasat)

 BRAINWARE UNIVERSITY
[BP402T] CLASS NOTES [Medicinal Chemistry-I]

In uterus: NSAIDs prolong gestation because of the inhibition of PGF2 in uterus. PGF2 is a
potent uterotropic agent and their biosynthesis by uterus increase dramatically in the hours
before parturition. Accordingly, some anti-infl ammatory drugs have been used as a colytic
agent to inhibit preterm labour.
In kidney: NSAIDs decrease renal blood flow and the rate of glomerular fi ltration in patients
with congestive heart failure, hepatic cirrhosis, and with chronic renal disease, in addition, they
prolong the retention of salt and water, this may cause oedema in some patients.
Classification
I. Salicylic acid derivatives: Aspirin, Diflunisal, Salsalate, Sulphasalazine.
II. p-Amino phenol derivatives: Paracetamol, Phenacetin.
III. Pyrazolidine Dione derivatives: Phenyl butazone, Oxyphenbutazone, Sulphin-pyrazone.
IV. Anthranilic acid derivatives: Mefenamic acid, Flufenemic acid, Meclofenamate.
V. Aryl alkanoic acid derivative.
a. Indole acetic acid: Indomethacin.
b. Indene acetic acid: Sulindac.
c. Pyrrole acetic acid: Tolmetin, Zormipirac.
d. Phenyl acetic (propionic) acid: Ibuprofen, Diclofenac, Naproxen, Caprofen, Fenoprofen,
Keto-profen, Flurbiprofen, Ketorolac, Etodaolac.
VI. Oxicams: Piroxicam, Meloxicam, Tenoxicam.
VII. Selective COX-2 inhibitors: Celecoxib, Rofecoxib, Valdecoxib.
VIII. Gold compounds: Auronofi n, Aurothioglucose, Aurothioglucamide, Aurothiomalate
sodium.
IX. Miscellaneous: Nabumetone, Nimesulide, Analgin.
X. Drug used in gout: Allopurinoll, Probenecid, sulphinpyrazone.
Sodium salicylate: It is used in medicine as an analgesic and antipyretic.
Sodium salicylate also acts as non-steroidal anti-inflammatory drug (NSAID),
and induces apoptosis in cancer cells and also necrosis. It is also a potential
replacement for aspirin for people sensitive to it.
Sodium salicylate is of the salicylate family and this compound is known to
trigger Reye's Syndrome in children and adults.

2021-22 Prepared by: Mr. Arnab Seth (Brainware University, Barasat)

 BRAINWARE UNIVERSITY
[BP402T] CLASS NOTES [Medicinal Chemistry-I]

Aspirin:
Aspirin, also known as acetylsalicylic acid, is used to treat pain, fever, or
inflammation.
Specific inflammatory conditions which aspirin is used to treat include
Kawasaki disease, pericarditis, and rheumatic fever.
Aspirin given shortly after a heart attack decreases the risk of death. Aspirin is also used long-
term to help prevent further heart attacks, ischaemic strokes, and blood clots in people at high
risk. It may also decrease the risk of certain types of cancer, particularly colorectal cancer.
One common adverse effect is an upset stomach. More significant side effects include stomach
ulcers, stomach bleeding, and worsening asthma.
Mefenamic acid:
Its name derives from its systematic name,
dimethylphenylaminobenzoic acid. Mefenamic acid is used to
treat moderate pain and menstrual pain.
Known mild side effects of mefenamic acid include headaches, nervousness, and vomiting.
Serious side effects may include diarrhea, hematemesis (vomiting blood), hematuria (blood in
urine), blurred vision, skin rash, itching and swelling, sore throat and fever. It has been
associated with acute liver damage.

Meclofenamate : Meclofenamate sodium is indicated for the relief of

mild to moderate pain.
Meclofenamate sodium is also indicated for the treatment of primary
dysmenorrhea and for the treatment
of idiopathic heavy menstrual blood loss. Meclofenamate sodium is
also indicated for relief of the signs and symptoms of acute and
chronic rheumatoid arthritis and osteoarthritis. It is not widely used in
humans as it has a high rate (30-60%) rate of gastrointestinal side
effects.

2021-22 Prepared by: Mr. Arnab Seth (Brainware University, Barasat)

 BRAINWARE UNIVERSITY
[BP402T] CLASS NOTES [Medicinal Chemistry-I]

Indomethacin
As an NSAID, indomethacin is an analgesic, anti-
inflammatory, and antipyretic.
ndometacin is a potent drug with many serious side effects and
should not be considered an analgesic for minor aches and
pains or fever. The medication is better described as an anti-
inflammatory, rather than an analgesic.
Sulindac (Clinoril)
Suindac is a yellow crystalline powder, very slightly
soluble in water, soluble in methylene chloride, and dilute
solutions of alkali hydroxides, sparingly soluble in alcohol.
The (Z) isomer of sulindac showed much more potent anti-
infl ammatory activity than the corresponding (E)-isomer.
The more polar and inactive sulphoxide is virtually the
only form excreted. It has analgesic, antipyretic, and anti-
infl ammatory properties. It is usually employed in the
treatment of rheumatic and muscular skeletal disorders, acute gouty arthritis, and osteoarthritis.
Tolmetin: Tolmetin is a nonsteroidal anti-inflammatory
drug (NSAID) of the heterocyclic acetic acid derivative
class. It is used primarily to reduce hormones that cause
pain, swelling, tenderness, and stiffness in conditions
such as osteoarthritis and rheumatoid arthritis,
including juvenile rheumatoid arthritis. In the United
States it is marketed as Tolectin and comes as a tablet or capsule. Tolmetin can increase the risk
of heart or circulatory conditions such as heart attacks and strokes. It should not be taken shortly
before or after coronary artery bypass surgery. Tolmetin can also increase the risk of
gastrointestinal conditions such as perforation or bleeding, which is fatal. Antacids can be taken
with tolmetin to relieve stomachaches that often occur. Overdose can result in
drowsiness, nausea, epigastric pain, and vomiting.
Zomepirac: Zomepirac is an orally effective nonsteroidal
anti-inflammatory drug (NSAID) that
has antipyretic actions. It was developed by McNeil
Pharmaceutical, approved by the FDA in 1980, and sold as
the sodium salt zomepirac sodium, under the brand
name Zomax. Due to its clinical effectiveness, it was
preferred by doctors in many situations and obtained a large share of the analgesics market;
however, it was subsequently withdrawn in March 1983 due to its tendency to cause
serious anaphylaxis in an unpredictable subset of the patient population.

2021-22 Prepared by: Mr. Arnab Seth (Brainware University, Barasat)

 BRAINWARE UNIVERSITY
[BP402T] CLASS NOTES [Medicinal Chemistry-I]

Diclofenac:
Diclofenac, sold under the trade names Voltaren among others, is a
nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and
inflammatory diseases such as gout.
Common side effects include abdominal pain, gastrointestinal
bleeding, nausea, dizziness, headache, and swelling. Serious side
effects may include heart disease, stroke, kidney problems, and stomach ulceration.
Ketorolac
Ketorolac is a white crystalline powder, soluble in water
and in methanol, slightly soluble in ethanol, practically
insoluble in methylene chloride. Ketorolac is a potent
analgesic indicated for the treatment of moderately severe
and acute pain.
Ibuprofen:
Ibuprofen is a medication in the nonsteroidal anti-inflammatory drug (NSAID) class that is used
for treating pain, fever, and inflammation.
This includes painful menstrual periods,
migraines, and rheumatoid arthritis.
Common side effects include heartburn and
a rash. Compared to other NSAIDs, it may
have fewer side effects such as
gastrointestinal bleeding. It increases the risk of heart failure, kidney failure, and liver failure.
Synthesis

2021-22 Prepared by: Mr. Arnab Seth (Brainware University, Barasat)

 BRAINWARE UNIVERSITY
[BP402T] CLASS NOTES [Medicinal Chemistry-I]

Naproxen:
The drug is fairly comparable to aspirin both in the management and control of disease
symptoms. Nevertheless, it has relatively lesser
frequency and severity of nervous system together with
milder GI-effects. It possesses analgesic, anti-
inflammatory, and antipyretic actions, and it is used in
the treatment of rheumatic arthritis, dysmenorrhea, and
acute gout.
Piroxicam:
It is used in the treatment of rheumatoid and osteoarthritis,
primary dysmenorrhoea, postoperative pain; and act as an
analgesic, especially where there is an inflammatory component.
As with other NSAIDs the principal side effects include:
digestive complaints like nausea, discomfort, diarrhoea and bleeds or ulceration of the stomach,
as well as headache, dizziness, nervousness, depression, drowsiness, insomnia, vertigo, hearing
disturbances (such as tinnitus), high blood pressure, oedema, light sensitivity, skin reactions
Phenacetin:
It is an analgesic and an antipyretic with similar
effectiveness as an aspirin. It has a greater potential for
toxicity (hemolytic anaemia and methemoglobinaemia)
than paracetamol.
Acetaminophen or Paracetamol:
Paracetamol, also known as acetaminophen is used to treat pain
and fever. It is typically used for mild to moderate pain relief. It is
often sold in combination with other medications, such as in many
cold medications. It is often sold in combination with other
medications, such as in many cold medications.
Paracetamol is generally safe at recommended doses. The recommended maximum daily dose
for an adult is three to four grams. Higher doses may lead to toxicity, including liver failure.
Phenazone (antipyrine):
Phenazone (also known as phenazon, antipyrine , or analgesine) is
an analgesic, a nonsteroidal anti-inflammatory drug (NSAID) and
an antipyretic. Antipyrine is a pyrazolone derivative that is 1,2-
dihydropyrazol-3-one substituted with methyl groups at C-1 and C-5
and with a phenyl group at N-2. Antipyrine is an analgesic and antipyretic that has been given by
mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases

2021-22 Prepared by: Mr. Arnab Seth (Brainware University, Barasat)

 BRAINWARE UNIVERSITY
[BP402T] CLASS NOTES [Medicinal Chemistry-I]

on drug-metabolizing enzymes in the liver. Phenazone was used before 1911 as an analgesic and
antipyretic. The dose was 5-20 grams, but on account of its depressant action on the heart, and
the toxic effects to which it occasionally gives rise it was replaced by phenacetin.
Phenylbutazone: Phenylbutazone is a nonsteroidal anti-
inflammatory drug (NSAID) for the short-term treatment of
pain and fever in animals.
Side effects of phenylbutazone are similar to those of other
NSAIDs. Overdose or prolonged use can cause
gastrointestinal ulcers, blood dyscrasia, kidney damage
(primarily dose-dependant renal papillary necrosis), oral
lesions if given by mouth, and internal hemorrhage.

2021-22 Prepared by: Mr. Arnab Seth (Brainware University, Barasat)