MOLECULAR MODIFICATIONS Special Processes

1
MOLECULAR MODIFICATIONSSpecial Processes
Ring closure, opening, or variation

• ALTERATIONS WHICH CHANGE MOLECULAR DIMENSIONS
  FLEXIBILITY

Formation of higher or lower homologs
Introduction of double bonds
2
MOLECULAR MODIFICATIONSSpecial Processes
Introduction of stereogenic centres

• ALTERATIONS WHICH CHANGE MOLECULAR DIMENSIONS
  FLEXIBILITY

Introduction, removal, replacement of bulky groups
3
ALTERATIONS WHICH CHANGE MOLECULAR DIMENSIONS
FLEXIBILITY
Ring Closure, Opening, Variation

• Physostigmine, Neostigmine, Pyridostigmine

• Chlorpromazine, Prochlorperazine, Thioridazine

• Dicumarol, Warfarin

• Amphetamine, Tranylcypromine

• Antihistamines

4
RING CLOSURE
Prochlorperazine
Chlorpromazine
Thioridazine
5
RING OPENING
Dicumarol
Amphetamine
Warfarin
Tranylcypromine
6
RING VARIATIONS
Clemizole
Tripelennamine
Cyclizine
Antazoline
7
RING VARIATIONS
Parathiazine
Clobenzepam
8
ALTERATIONS WHICH CHANGE MOLECULAR DIMENSIONS
FLEXIBILITY
Formation of Higher or Lower Homologs

• Regular increase in activity

• Irregular effect

• Activity alternates

• Activity changes

9
ALTERATIONS WHICH CHANGE MOLECULAR DIMENSIONS
FLEXIBILITY
Introduction of Double Bonds

• Rigidity

• Stereochemical implications

• Activity

cortisone
prednisolone
10
ALTERATIONS WHICH CHANGE MOLECULAR DIMENSIONS
FLEXIBILITY
Introduction of Stereogenic Centres

• terbutaline - gt 30001 trachea
  relaxation

• flecainide -
  antiarrhythmic

• tranylcypromine gt - 21 MAO
  inhibition

• arylpropionic acids S gt R
  antiinflammatory

11
ALTERATIONS WHICH CHANGE MOLECULAR DIMENSIONS
FLEXIBILITY
Introduction, Removal, Replacement of Bulky Groups
1.
Agonists Antagonists

• acetylcholine

• noradrenaline

• serotonin

2.
Change in relative activity

• benzylpenicillin

12
ALTERATIONS WHICH CHANGE MOLECULAR DIMENSIONS
FLEXIBILITY
Agonists Antagonists
acetylcholine
tridihexethyl
propranolol
noradrenaline
13
ALTERATIONS WHICH CHANGE MOLECULAR DIMENSIONS
FLEXIBILITY
Agonists Antagonists
serotonin
methysergide
14
ALTERATIONS WHICH CHANGE MOLECULAR DIMENSIONS
FLEXIBILITY
Change in relative activity
benzylpenicillin
(lactamase labile)
methicillin
(lactamase stable)