SAR Flashcards
When two carbon atoms separate the ring from amino group
Greatest sympathomimetic activity
Effect of increasing the size of alkyl substituents on the amino group
Increases beta-receptor activity (isoprenaline) but, N-methylation increase the potency of primary amine (e.g. phenylephrine)
Possible substitution on aromatic nucleus
- OH position
- Presence or absence of both -OH groups
Maximal alpha and beta activity depends on
the presence of hydroxyl groups on position 3 and 4.
OH-on position 3 and 5 confers
…beta receptor selectivity on compounds with large amino substituents (terbutaline, metaproterenol - to relax bronchial smooth muscle but less cardiac stimulation)
SAR and COMT action
Compounds without one or both hydroxyl substituents are not acted upon by COMT and their oral effectiveness and duration of action prolonged
Methoxy substituents at 2 and 5 has…
…highly selective alpha stimulating activity and large doses block beta-receptors. Albuterol is exempted sha.
When groups other than hydroxyl are substituted on the group, what is the drug’s effect?
It’s alpha potency reduces
MAO and SAR
Substitution on the alpha carbon blocks MAO activity, eg ephedrine and amphetamine
Substitution on the beta-carbon atom
…generally decreases action within the CNS largely because it lowers lipid solubility but enhances agonist activity at both alpha and beta adrenergic receptor.
Ephedrine is less potent than methamphetamine as a central stimulant, it is more powerful in dilating bronchioles and increasing BP and HR
Optical isomerism and SAR
Levo on Beta - Peripheral activity
D on alpha - Potency
Substitution on either alpha or beta carbon yields optical isomers. Levo-substitution on beta-carbon confers the greater peripheral activity; L-ADR and L-NA are 10X AS POTENT as their unnatural D-isomers.
D-sub (optical isomerism) on alpha
More potent compound- D-AMP more potent than L-amp in central but not peripheral
