Beta agonists & Antimuscarinics Flashcards
(15 cards)
What receptors do beta-agonists act on, give an example.
Adrenergic Receptors - e.g. Salbutamol
What receptors do antimuscarinics act on, give an example
Nicotonic/Muscarinic Receptors, e.g. Ipratropium
Outline medicinal chemistry strategies - 2
- Starting from a lead compound, establish structure activity relationship (SAR)
- Make specific structural modifications to the lead, converting it into a selective agonist or antagonist.
Structural modifications to enhance activity of a molecule - 4
- Chain extension
- conformational restriction
- group shifting
- chiral switching.
What are lead compounds?
Prototype chemical structures with a desired biological activity.
How are lead compounds found - 5
- Natural receptor ligands → Ach, noradrenaline
- Collections of synthetic compounds
- Existing drugs
- Natural products → muscarine
- Computer-aided rational design
What conclusions can be drawn from the SAR of Acetylcholine - 4
- Can predict Oxygens are responsible for H-bonds
- Quaternary nitrogen involved in ionic interaction
- Methyl groups fit into small hydrophobic pockets
- Size shows tight fit between Ach & binding site - little room for variability.
Key features for designing an antagonist/agonist - 2
- Functional group interactions, & bond rotatability - result in a large number of possible conformations.
- The active conformation does not always equal the most stable conformation
Two cholinergic receptor types
Nicotinic & Muscarinic
Describe two ACh analogues
- Nicotine & L-Muscarine are rigid Ach analogues
- Have bond rotations locked in a ring, limiting conformation possibilities
What can help in prototype structure identification?
By overlaying structures you can identify which structures are needed for the key interactions between molecule & receptor.
Describe the beta1+2-adrenoceptors function - 2
- Activation of Beta2-Adrenoceptors relaxes smooth muscle, predominantly in the airways
- Activation of Beta1-Adrenoceptors contracts cardiac muscles, predominantly in the heart.
How are adrenaline & noradrenaline classified - 2
Adrenaline & noradrenaline are catecholamines because they contain:
- A catechol group (a benzene ring with two hydroxyls)
- An amine group (on a short side chain)
Outline some of the key functional groups of this catecholamine - 4
- Phenol(meta+para) - H-bonds
- Alcohol - H-bonds
- Protonated amine - Ionic Interaction
- Aromatic ring - Van der Waals interactions
Chirality effect on molecules
Different enantiomers can have different binding actions.
