Lecture 3 Concept Notes Flashcards
What do drugs in similar pharmacologic classes share?
Usually share the same structural features
Examples of similar features?
Basic nitrogen
Aromatic ring
Esters
Phenols
Aliphatic Carbons or alicyclic moieties
What does stereochemistry permit a molecule to do?
Orient itself in a unique position
Pharmacophore
Steric & electronic features that is necessary to ensure optimal interactions with a specific target to reach a desired biological response
Chirality in the body
Biological targets are often also chiral, as well as amino acids, carbohydrates & phospholipid
Chirality is important in drug discovery. Why?
It can affect the whether or not the drug is active, and some enantiomers of drugs can be toxic or tetratogenic
+ Epinephrine is less active than (-). Why?
On the + enantiomer, the OH group is pointing away from the receptor and the drug will not occupy it. On the - enantiomer, the OH group is pointing towards the receptor and it will be occupied
Constitutional isomers
Same atoms different connectivity
Stereoisomers
Same atoms, same connectivity, different stereochemistry
Conformational isomers
Changes are made about a single bond rotations
Geometric Isomers
Changes are made around a double bond
Optical Isomers
isomers that can rotate polarized plane light.
Diastereomers & enantiomers
enantiomers
non superimposable mirror images of one another
sp3 chiral carbons
Properties of an aneantiomer
physical and chemical properties are idenitcal
Enantionmers can differ how in binding
One enantiomer of a drug may be inactive or less active
How can enantiomers be useful?
Useful in accessing chiral precursors for organic synthesis
How were enantiomers discovered
When two of the same drug were placed in front of a polarizing filter and it was realized that they were rotating the plane of light in different ways
D/L Designation
D= Right
L = Left
Do problems on slides
Cahn-Ingold Prelog Rule
S= counter clockwise
R= clockwise
IF lowest priority is on a wedge, change the S-R and vise versa
Increasing priority
-H
-CH3
- N
-O
- SH
-Cl
-Br
-I
How to determine if two molecules are enantiomers of eachother
Check the configuration on the chiral carbons. If BOTH chiral carbons change, then they are enantiomers
(R)(R) –> (S)(S)
How to determine if two molecules are diasteromers of eachother?
Check the configuration on the chiral carbons. If ONLY ONE chiral carbons change, then they are diasteromers
(R)(R) –> (S)(R)
Diasteromers
Can have different physical and chemical properties
Not mirror images
Non-super imposable
Erythro
Two groups that are adjacent to eachother the are on the same side
Threo
Two groups that are adjacent to eachother that areon the opposite sides
Meso Compounds
Optically inactive. Molecule has a plane of symmetry. achiral diasteromer due to an internal plane of symmetry
How to determine how many stereoisomers a chiral drug will have?
Count the stereogenic centers. Use the formula 2^n to determine
