Unit 1 Part 1

By Sonali Arora
 Course Content
Study of the development of the following classes of drugs, Classification, mechanism of action, uses of drugs
mentioned in the course, Structure activity relationship of selective class of drugs as specified in the
course and synthesis of drugs superscripted (*).
Unit 1 Part 1
Antihistaminic agents: Histamine, receptors and their distribution in the human body.
H1–antagonist: Diphenhydramine hydrochloride*,Triprolidine hydrochloride*, Promethazine
hydrochloride*, Dimenhydrinate, Doxylamines succinate, Clemastine fumarate,
Diphenylphyraline hydrochloride, Triphelenamine hydrochloride, Chlorcyclizine hydrochloride,
Meclizine hydrochloride, Buclizine hydrochloride, Chlorpheniramine maleate, Phenidamine
tartarate, Trimeprazine tartrate, Cyproheptadine hydrochloride, Azatidine maleate, Astemizole,
Loratadine, Cetirizine, Levocetrizine Cromolyn sodium
H2-antagonists: Cimetidine*, Famotidine, Ranitidine.
Gastric proton-pump inhibitors: Omeprazole, Lansoprazole, Rabeprazole, Pantoprazole.
Unit 1 Part 2
Anti-neoplastic agents:
Alkylating agents: Meclorethamine*, Cyclophosphamide, Melphalan,
Chlorambucil, Busulfan,Thiotepa.
Antimetabolites: Mercaptopurine*, Thioguanine, Fluorouracil, Floxuridine, Cytarabine,
Methotrexate*,Azathioprine.
Antibiotics: Dactinomycin, Daunorubicin, Doxorubicin, Bleomycin.
Plant products: Etoposide,Vinblastin sulphate,Vincristin sulphate.
Miscellaneous: Cisplatin, Mitotane.
Diphenhydramine hydrochloride

Also known as -
- 2-(diphenylmethoxy)-N,N-dimethylethanamine hydrochloride
-Benadryl

Diphenhydramine is used to relieve red, irritated, itchy, watery eyes; sneezing; and
runny nose caused by hay fever, allergies, or the common cold. Diphenhydramine
is also used to relieve cough caused by minor throat or airway irritation.
Synthesis
A
B
Triprolidine hydrochloride

C19H22N2.HCL
2-[(E)-1-(4-methylphenyl)-3-
pyrrolidin-1-ylprop-1-
enyl]pyridine; hydrochloride

Triprolidine is an antihistamine
used to relieve symptoms
of allergy, hay fever, and
the common cold. These
symptoms include rash,
watery eyes, itchy
eyes/nose/throat/skin, cough,
runny nose, and sneezing.
Promethazine hydrochloride

C17H20N2S.HCL
N,N-dimethyl-1-
phenothiazin-10-ylpropan-
2-amine;hydrochloride

Promethazine is used to prevent and

C
Dimenhydrinate
 Dimenhydrinate(combination drug of
diphenhydramine and 8-
Chlorotheophylline)
 C24H28ClN5O3
 2-benzhydryloxy-N,N-
dimethylethanamine;8-chloro-1,3-
dimethyl-7H-purine-2,6-dione
 Dimenhydrinate is used to prevent
and treat nausea, vomiting,
and dizziness caused by motion
sickness.
 It works by preventing problems with
body balance.
Doxylamines succinate
 C21H28N2O5
 butanedioic acid;
 N,N-dimethyl-2-(1-phenyl-1-pyridin-
2-ylethoxy)ethanamine
 Doxylamine is an antihistamine, used
to relieve symptoms of allergy, hay
fever, and the common cold.
This medication works by blocking
certain natural substances
(histamine, acetylcholine) that your
body makes. This effect helps to
relieve allergy/cold symptoms such
as watery eyes, runny nose,
and sneezing.
Clemastine fumarate
 C21H26Cl
 (E)-but-2-enedioic acid;(2R)-2-
[2-[(1R)-1-(4-chlorophenyl)-1-
phenylethoxy]ethyl]-1-
methylpyrrolidine
 Clemastine fumarate is the
fumaric acid salt of clemastine.
An antihistamine with
antimuscarinic and moderate
sedative properties, it is used for
the symptomatic relief of allergic
conditions such as rhinitis,
urticaria, conjunctivitis and in
pruritic (severe itching)
skin conditions.
Diphenylpyraline hydrochloride
 C19H23NO
 4-benzhydryloxy-1-
methylpiperidine;hydrochlorid
e
 Diphenylpyraline is a member
of the class of piperidines that
is the benzhydryl ether
derivative of 1-methyl-4-
hydroxypiperidine. A sedating
antihistamine, it is used as the
hydrochloride for the
symptomatic relief of allergic
conditions including rhinitis
and hay fever, and in
pruritic skin disorders.
Triphelenamine hydrochloride
 C16H22ClN3
 N'-benzyl-N,N-dimethyl-N'-
pyridin-2-ylethane-1,2-
diamine;hydrochloride
 Used to treat the effects of colds
and allergies. Tripelennamine is
an antihistamine. Histamine, acting
on H1-receptors, produces pruritis,
vasodilatation, hypotension,
flushing, headache, tachycardia, and
bronchoconstriction. Histamine
also increases vascular
permeability and potentiates pain.
Chlorcyclizine hydrochloride
 C18H21ClN2 .HCl
 1-[(4-chlorophenyl)-
phenylmethyl]-4-
methylpiperazine;hydrochloride
 Chlorcyclizine is a first
generation phenylpiperazine class
antihistamine used to treat
urticaria, rhinitis, pruritus, and
other allergy symptoms.
Chlorcyclizine also has some
local anesthetic, anticholinergic,
and
antiserotonergic properties,
and can be used as an antiemetic.
Meclizine hydrochloride
 C25H27ClN2 .HCl
 1-[(4-chlorophenyl)-
phenylmethyl]-4-[(3-
methylphenyl)methyl]piperaz
ine hydrochloride
 Meclizine or Meclizine
Hydrochloride is used as an
anti-vertigo drug to control
the symptoms of vertigo and
imbalance. Meclizine is an
antihistamine agent with
antiemetic and
antispasmodic properties.
Buclizine dihydrochloride
 C28H35Cl3N2
 1-[(4-tert-butylphenyl)methyl]-4-
[(4-chlorophenyl)-
phenylmethyl]piperazine;dihydro
chloride
 Buclizine hydrochloride, a
piperazine derivative, is a
sedating antihistamine with
antimuscarinic and moderate
sedative action. Buclizine is used
in the prevention and treatment
of nausea, vomiting, and
dizziness associated with motion
sickness.
Chlorpheniramine maleate
 C20H23ClN2O4
 (Z)-but-2-enedioic acid;3-(4-
chlorophenyl)-N,N-dimethyl-3-
pyridin-2-ylpropan-1-amine
 Chlorpheniramine relieves
red, itchy, watery eyes; sneezing;
itchy nose or throat; and runny
nose caused by allergies, hay
fever, and the common
cold. Chlorpheniramine helps
control the symptoms of cold
or allergies but will not treat the
cause of the symptoms or speed
recovery.
Phenidamine tartarate
 C23H25NO
 (2R,3R)-2,3-
dihydroxybutanedioic
acid;2-methyl-9-phenyl-
1,3,4,9-
tetrahydroindeno[2,1-
c]pyridine6
 It is used to treat symptoms
of the common cold and
allergies, such as sneezing,
itching, rashes, and hives.
Trimeprazine tartrate
 C40H50N4O6S2
 (2R,3R)-2,3-
dihydroxybutanedioic
acid;N,N,2-trimethyl-3-
phenothiazin-10-ylpropan-1-
amine
 Trimeprazine (also known as
Alimemazine), a phenothiazine
used as antipsychotic drug. This
drug is used in Russia under
brand name TERALIGEN and
has anti-histamine, sedative, and
anti-emetic (anti-nausea) effects.
Teraligen is used to treat
neurosis, depression and anxiety
of different origins.
Cyproheptadine hydrochloride
 C21H22ClN
 1-methyl-4-(2-
tricyclopentadeca-
1(15),3,5,7,9,11,13-
heptaenylidene)piperidine;hydro
chloride
 Cyproheptadine relieves red,
irritated, itchy, watery eyes;
sneezing; and runny nose caused by
allergies, irritants in the air, and hay
fever. It may also be used to relieve
the itching of allergic skin
conditions, and to treat hives,
including hives caused by exposure
to cold temperatures and by
rubbing the skin.
Azatidine maleate
 C28H30N2O8
 (Z)-but-2-enedioic acid;2-(1-
methylpiperidin-4-ylidene)-4-
azatricyclopentadeca-
1(15),3(8),4,6,11,13-hexaene
 Azatadine is an antihistamine,
which blocks the effects of the
naturally occurring chemical
histamine in the body. Azatadine
is used to
treat sneezing; runny
nose; itching, watery
eyes; hives; rashes; and other
symptoms of allergies and the
common cold.
Astemizole
 C28H31FN4O
 1-[(4-fluorophenyl)methyl]-N-
[1-[2-(4-
methoxyphenyl)ethyl]piperidin-
4-yl]benzimidazol-2-amine
 Astemizole is an antihistamine.
Antihistamines prevent sneezing,
runny nose, itching and watering
of the eyes, and other allergic
symptoms. Astemizole is used
to treat allergies, hives
(urticaria), and other allergic
inflammatory conditions.
Loratadine
 C22H23ClN2O2
 ethyl 4-(13-chloro-4-
azatricyclopentadeca-
1(11),3(8),4,6,12,14-hexaen-2-
ylidene)piperidine-1-carboxylate
 Loratadine is an antihistamine
that reduces the effects of natural
chemical histamine in the body.
Histamine can produce symptoms
of sneezing, itching, watery eyes,
and runny nose. Loratadine is
used to treat sneezing, runny
nose, watery eyes, hives, skin rash,
itching, and other cold or allergy
symptoms.
Cetirizine
 C21H25ClN2O3
 2-[2-[4-[(4-chlorophenyl)-
phenylmethyl]piperazin-1-
yl]ethoxy]acetic acid
 Cetirizine is an antihistamine
used to relieve allergy
symptoms such as watery eyes,
runny nose, itching eyes/nose,
sneezing, hives, and itching. It
works by blocking a certain
natural substance (histamine)
that your body makes during
an allergic reaction.
Levocetrizine
 C21H25ClN2O3
 2-[2-[4-[(R)-(4-chlorophenyl)-
phenylmethyl]piperazin-1-
yl]ethoxy]acetic acid
 Levocetirizine is used to
relieve runny nose; sneezing; and
redness, itching, and tearing of
the eyes caused by hay fever,
seasonal allergies, and allergies
to other substances such as dust
mites, animal dander, and mold.
It is also used to treat
symptoms of hives, including
itching and rash.
Cromolyn sodium
 C23H14Na2O11
 disodium;5-[3-(2-carboxylato-
4-oxochromen-5-yl)oxy-2-
hydroxypropoxy]-4-
oxochromene-2-carboxylate
 Cromolyn sodium is used to
treat the symptoms of a
condition called mastocytosis,
which can
cause diarrhea, nausea, vomiting
, headaches, stomach pain, itchy
skin, and flushing (warmth or
redness under the skin).
Ulcers
Acid secretion in stomach
Anti ulcer drug classification

(PPIs)
H2-receptor antagonists
 Histamine H2-receptor antagonists, also known as H2-
blockers, are used to treat duodenal ulcers and prevent
their return. They are also used to treat gastric ulcers and
for some conditions, such as Zollinger-Ellison disease, in
which the stomach produces too much acid.
 Mechanism of Action - H2RAs decrease gastric acid
secretion by reversibly binding to histamine H2 receptors
located on gastric parietal cells, thereby inhibiting the
binding and action of the endogenous ligand
histamine. H2 blockers thus function as
competitive antagonists.
Mechanism of Action
H2RAs
SAR
Cimetidine
 C10H16N6S
 1-cyano-2-methyl-3-[2-[(5-methyl-1H-imidazol-4-
yl)methylsulfanyl]ethyl]guanidine
 Cimetidine is a stomach acid reducer that is used to
treat and prevent certain types of stomach
ulcer. Cimetidine is also used to treat gastroesophageal
reflux disease (GERD), when stomach acid backs up into
the esophagus and causes heartburn.
A
Famotidine
 C8H15N7O2S3
 3-[[2-(diaminomethylideneamino)-1,3-thiazol-4-
yl]methylsulfanyl]-N'-sulfamoylpropanimidamide
 Famotidine is used to treat ulcers of
the stomach and intestines and to prevent intestinal
ulcers from coming back after they have healed.
This medication is also used to treat certain stomach and
throat (esophagus) problems (such as erosive esophagitis,
gastroesophageal reflux disease-GERD, Zollinger-Ellison
syndrome). It works by decreasing the amount of acid
your stomach makes. It relieves symptoms such
as cough that doesn't go away, stomach pain, heartburn,
and difficulty swallowing.
Ranitidine
 C13H22N4O3S
 (E)-1-N'-[2-[[5-[(dimethylamino)methyl]furan-2-
yl]methylsulfanyl]ethyl]-1-N-methyl-2-nitroethene-1,1-
diamine
 Ranitidine is used to treat ulcers of
the stomach and intestines and prevent them from
coming back after they have healed. This medication is
also used to treat certain stomach and throat (esophagus)
problems (such as erosive esophagitis, gastroesophageal
reflux disease-GERD, Zollinger-Ellison syndrome). It
works by decreasing the amount of acid your stomach
makes. It relieves symptoms such as cough that doesn't go
away, stomach pain, heartburn, and difficulty swallowing.
Gastric proton-pump inhibitors (PPIs)
How PPIs work?
Omeprazole
Lansoprazole
Rabeprazole
Pantoprazole