Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
17 Cards in this Set
- Front
- Back
What is bioisosterism? Why do we do it?
|
Changing out functional groups.
When a drug lead shows toxicity or we wish to improve on a drug, - can improve pharmacokinetic properties (ie t½) |
|
What is classical classification?
|
any group that have the same number of valence electrons, though they may differ in number of atoms
- more structure than function, so not very relevant to us |
|
What is non-classical classification?
|
do not have same number of atoms and do not fit steric and electronic rules of classical classification, but DO produce a similarity in biological activity
- eg they are functionally equivalent |
|
What is the reasoning behind marketing chiral atoms as pure enantiomers?
|
1. potentially safer than racemates
2. economic incentive to extend patent life of racemates |
|
Isosteres
|
native functional groups of interest
|
|
Enantiomers
|
mirror images
|
|
Diastereomers
|
molecules with two or more chiral centers and are NOT mirror images
|
|
What is the relationship between the number of sterioisomers a drug has and the risk of side effects?
|
The higher the number of stereoisomers, the more likely you are to have side effects
|
|
What is the difference between Z and E isomers?
|
Z isomers are cis to the double bond
E isomers are trans to the double bond They are geometric isomers |
|
Thalidomide
|
The morning sickness drug that caused birth defects
- acidic proton on a chiral center is easily deprotonated in vivo which tautomerizes back to the racemere Has renewed interest as an anti-cancer drug due to its anti-angiogenic properties (angiogenesis is critical step in metastatis) |
|
How can fluorine make a molecule more stable?
|
By replacing an easily deprotonated proton with F. No base can pull off the F
|
|
Which is the more active enantiomer of Omeprazole?
Why? |
S is more active (Esomeprazole/Nexium)
- R is metabolized by a CYP450 that show a high degree of polymorphism |
|
What are the strategies for preparation of pure enantiomers of chiral compounds?
|
1. Make use of nature's "chiral pool" (add final touches to a natural sugar, aa,etc.)
2. Separate racemic mixture by converting into diasteromeric salts that can be separtated (inexpensive, but needs acid or base functional group) 3. Use an enzyme to create chiral center or resove enantiomeric mixture Adv: enzymes are specific Dis: enzymes are specific 4. Use a synthetic chiral catalyst (stereochemical induction) - increasing number of chiral reagents available |
|
How can gauche be the preferred conformation?
|
functional groups may share electron density that makes the conformation more favorable
|
|
Bioactive conformation∆
|
only one conformation of a ligand will be bioactive,
hopefully the energy of binding is greater than the energy of the conformation conversion ∆Gbind = ∆Ginter - ∆Gconf (needs to be favorable) Usually, ∆Ginter is negative while ∆Gconf is positive |
|
Conformational restriction
Class Example? |
a means of pre-organizing drug structure to be more like target bound species than a free species
- eliminates need of drug to overcome ∆Gconf Examples: - Cholrismate Mutase - Penicillins |
|
isosterism
|
mimicking of specific functionalgroups that make key interactions with a given target
|