The document discusses the structure-activity relationship of morphine. It identifies several functional groups that are important for morphine's analgesic activity. The phenolic OH group and aromatic ring allow for hydrogen bonding and van der Waals interactions with receptors. The amine group enables ionic bonding. Masking or removing these functional groups, such as through acetylation, reduces morphine's potency. Only the natural enantiomer of morphine exhibits activity, as it properly fits receptor sites.

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