5) Ipratropium bromidL ’

Atopl is act with Isopropyl bromid1 and girt.

H A R

Synihesu
M E

to ipratopium bromdde
RM

(Anopin) C A R E W

(1op>opyl bromidi) 87t04

R

(Lprattopium bromida)
P H A R . ?

" Mechanim cf achion ’

armmoniom CompoUnd which bloks MUS Carindc
t ik qvalonary
acchyl cholíia Kceptos.
non- selective MUsCavinic
- t is artagonst.
REWE

- Used in tu teatmunt -Acthma

teatmunt of cronie bstructive pulmonary di caasn (voPD).
 Neostiqmin *’ NU
PHARM

N
+

OH
Chiorodímeh¡l Carbomale
(3- dimehyl CDimekuyl (arbomoyl cloride]
anäno pkandl]

menylahion
Neostiamint
CNeDstigmi n
" Mechandsm
P H A R M A of actlon bromida]

indichy stimulales both muscorinic and niCoBonic

Hauptos.
-+ bind anionic aud esteuc sie of
cholineseou and dok t ativity of qcetyldholinesttrau
REWE
" Uses
- Used in tu teahmunt of nuyasthenia qravit
also usLd ín glaucoMa ( lowen rtraoulan. presurc).
 i) (orbachoí -’
ARMI

P H A R

Syntheus
Coh
HO CH-ON-c
EWEL
E W E

CHh
cholin.
chlorida

- It is pepaed buy Hattng dhlia

chlovida with phosgn in chloroform Ng-0-y-Uy-GLon
Bolution follouwed bs teatmut of arbachol
the poduc with ammonjum hydroxld
qive aba chol
PHARN'3
"Mechaism of ation ’
-Bind with both Mus (arinie ad nicotinic
-I i not inacivated by choliustea so t adiom
MOR prolongud than Ochylcholins
R E W E

-Used in Case of saver chronic qlaucoma.

qive intra -ouwlariy to produca niosis fn ocwlar surguy and
to eduCQ post operahve risk.
 CAR

4) DiydoradA. hydro cloudu -’

"M.o.A
- ats as non selecive SMoth
MusdL elat: "Hd
- It has
sprifit atidoliangic H A R M A

effect at muscarinic Heepto

R N has diect efleu on sMDoth
MUIls.

www.carewellpharma.in (free notes)

visit website to download free pdf notes

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used in th treatmt of irilabl bowel synadrom

also uud in C A
Heatmunt
R E W
of E L ( I

aud dudonl uer.

A R I

P H A

Syntheis oF Dicylomin. hydiodloud

CEN 1-ypuDbiyuowxoue

WE

(Gyano tycdo (ayclokuxyl I-e4-h-N

hexan) bonidi]
(I-upuobicyloluxaui) CA

HCI
(Diuloonin]
SAR OF CHOLINERGIC DRUGS

CHs
Acetylcholine (ACH)
c CH3
Acety CH3 group is
substituted with at
least one phenyl ring
les

for antimuscarinic
activity

R6

Page |6
ISI-15, RICO Institutional Area, Sitapura, Tonk Road, Jaipur - 302021
Email: jcpjaipur@gmail.com Website: jcpjaipur.com

Estd. 2003

JAIPUR COLLEGE OF PHARMACY, JAIPUR

B.PHARMACY, SECOND YEAR, FOURTH SEMESTER
MEDICINAL CHEMISTRY-I
Prepared by: Mrs. Nisha Dhir
Je

1. Substitutions at a-carbon with respect to ester group

1. May be a hydrogen atom, a hydroxyl
group, a hydroxymethyl group, or a
carboxamide
2. Hydroxyl group or a hydroxymethyl group,
the antagonist usually is more potent
R, and R, should be carbocyclic or heterocyclic
rings (phenyl, cyclohexyl, cyclopentyl) for R
(maximal antagonist potency

Substitution of naphthalene rings at R, and R, affords inactive compounds,

because of steric hindrance at the muscarinic receptor.

Bigger R, and R, groups bind to the hydrophobic region outside the Ach
receptor site

The hydroxyl group at R, presumably increases binding strength by participating

in a hydrogen bond interaction at the receptor.

2. Changes at ester group

This substituent may also be an

ether oxygen, or it may be absent
completely. Ester group provides most potent
anticholinergic activity

R
R Re
R
SAR of cholinolytic agents

1. Anticholinergic agents are bulky. They combine with muscarinic receptors

and shield the binding site from acetylcholine. The general structure of the
compounds in this category is

2. Substituent R1 should be carbocyclic or heterocyclic ring for maximal

antagonist activity.
3. Substituent R2 should be a hydrogen atom, hydroxy group, hydroxymethyl
group, or methyl group.
4. The nature of the group X effects only the duration of action, the

physicochemical properties and the side effects of the drug molecule but not its
ability to bind with the receptor.
Page |19
ISI-15, RIICO Institutional Area, Sitapura, Tonk Road, Jaipur-302021
Email: jcpjaipur@gmail.com Website: jcpjaipur.com

Estd. 2003

JAIPUR COLLEGE OF PHARMACY, JAIPUR

B.PHARMACY, SECOND YEAR, FOURTH SEMESTER
MEDICINAL CHEMISTRY-I
Prepared by: Mrs. Nisha Dhir

5. There is a limitation for the N-substitution. Optimal potency is associated

with 2-3 ethyl groups.
6. The stereochemistry at the benzylic carbon is critical for muscarinic
antagonist activity. Any compound that can place the phenyl group in the same
absolute configuration as depicted in the general formula above will have potent
muscarinic antagonist activity
7. The phenyl ring cannot tolerate any their substituent than F at the p-position
without losing its antagonist activity
8. A negative site for binding of the positive charged N; quaternary amines have
formal positive charge while tertiary amines have a positive charged proton
CH,

Atropine CH,

9. Atropine is a racemic mixture (equal number of d- and 1-isomers) and like

most chemicals acting on the peripheral nervous system, atropine is
stereospecific; 1-isomer (1-hyoscyamine) is 250 times more active than the d
isomer

10. The presence of an N-methyl group on atropine or scopolamine changes the

activity of the ligand, possibly by preventing a close interaction between the
ligand and the membrane or lipophilic sites on the receptor. The methyl group
also prevents the penetration into the brain