Poster presentation

1. DEPARTMENT OF CHEMISTRY OF GC. WOMEN UNIVERSITY, SIALKOT.
STRUCTURE ACTIVITY REALTIONSHIP(SAR) OF MORPHINE:
PRESENTED TO;
DR. AYESHA
PRESENTED BY:
BS
2-BUSHRA
20-ANAM FATIMA
MSC
4-ALEESHA
14-RABIA
18-SUNDAS
23-AMNA
PHENOLIC OH:
.
INTRODUCTION:
Structure-activity relationship:
 The structure–activity relationship (SAR) is the relationship
between the chemical or 3D structure of a molecule and its
biological activity.
 It Identifies the functional groups that are important for
binding and activity by:
i. Masking or removing a functional group
ii. Testing the analogue for activity.
Morphine:
6-ALCOHOL:
The alcohol group at 6th position is not essential for the
activity
The alcohol group at 6th position is masked by acetyl group
forming 6- acetyl morphine.
6-acetylmorphine is less polar than morphine and reach the
receptor cell more fastly.
Heroin is another compound in which both the OH groups are
masked.
It is more powerful than morphine because it enters the brain
more easily
It is less powerful than 6-acetylmorphine because the 3-acetyl
group has to be removed before it can act.
THE N-METHYL GROUP:
 The N-oxide and the N-methyl quaternary salts of
morphine are inactive which suggest that the
introduction of charge destroys analgesic activity.
 If the same compounds are injected to brain they give
different results but have similar activity.
 It’s because nitrogen atom is ionized when bonded to
the receptor.
 Nitrogen is essential for activity even when methyl is
replaced with hydrogen so there is no effect of methyl
on activity.
ETHER BRIDGE:
 The ether bridge is not essential in morphine because
it does not show any activity.
ROLE OF AROMATIC RING:
 Planner benzene ring shows efficient binding
with receptor
ROLE OF DOUBLE BOND AT 7, 8:
 It has no effect on activity of morphine
ACTIVITY OF MORPHINE:
There are three important functional groups for the
analgesic activity of morphine. Which are
 OH group for H-bonding.
 Aromatic ring for vander wall interaction.
 Amine for ionic bonding.
STEREOCHEMISTRY:
 Morphine is an asymmetric molecule containing five chiral centres.
It exists naturally as single enantiomer
 Morphine was firstly sythesized in two enantiomeric form.
 Natural isomer
 unnatural isomer
 Only the natural isomer showed the analgesic activity as it fits into the
receptor site properlyR= Me Codeine
R= Et Ethylmorphine
R=Acetyl 3-acetylmorphine
Analgesic
activity
 All these morphine analogues mask the polar phenyl
group so decreases the activity.
 codeine is only 0.1 per cent as active as morphine.
 Masking phenol is bad for activity.
 codeine can be metabolized in the liver to give
morphine. So, it is used as prodrug for morphine.
 Isolated from opium in large quantities
 One of the most effective painkiller available to
medicine
 structurally similar to small pain-regulating peptides
made by our body, such as leucine-enkephalin.
Reactions:
N CH3
H
H
O
HO
HO
N CH3
H
H
O
HO
HO
N CH3
H
H
O
HO
HO
N CH3
H
H
O
HO
N CH3
H
H
O
H3CO
N CH3
H
H
O
C2H5O
N CH3
H
H
O
H3COCO
(CH3)2SO4
NaOH
(C2H5)2SO4
NaOH
Ac2O
HO
HO
HO
HO
FUNCTIONAL GROUPS OF MORPHINE