Lecturw 6 Flashcards
(20 cards)
SAR for anti microbial acidity
Differ from normal SAR
Replacing benzene decease
Adding substitute decrease
Sulfa drugs
Mimic and inhibit the biosynthesis of DHF
Anti diabetic activity
Increase insulin production
Diuretic activity
Increase water excretion
Inhibited ion channels
Paclitaxel activity
Replace HBD with HBA will decrease effect
Drug in-likeness
Non drugs show up active giving false positives
Bind number of receptors
Self aggression
Larger therapeutic index
Greater margin of safety
More life-threatening disease ➡️
The lower the acceptable TI
Branched-chain groups
less lipophilic, lower potency, bad
Cyclization
Does not affect potency but increases lipophilicity and decreases metabolism
Changes from bioisosteric replacements
Allows you to tinker with whichever parameters are necessary to increase solubility or reduce toxicity
This includes size, shape, electron distribution, lipid solubility, water solubility, etc
Structural
size, shape, H bonding
Receptor interactions
Lipid and H2O solubility
Pharmacokinetics
Lipophilicity, hydrophilicity, pKa and H bonding
Metabolism
Chemical reactivity
Phenylalanine peptidomimetrics
Increased lipophilicity and conformational rigidity
Better absorption and poor recognition by proteases
Boric acid as a CO2 H bioisostere
Non-toxic readily synthesized
Example: bortezomib
Boronia acid as a proteasome inhibitor
Tighter binding and enhanced bioactivity
Circumventing metabolism
Prodrug designed to be slowly converted to active drug to prolong plasma levels
Esther prodrug
Used to protect acid function as a master
