Medchem Flashcards
Strong bases have
high solubility
Weak bases have
low solubility
H-Bond donors
Hydrogens that are attached to N or o
H-Bond acceptors
O and N
In an amide
N cannot accept H-bonds
An increase in one pH unit, means
an 10-fold increase in [H+]
Log P >0
more drug in octanol
Log P<0
more drug in water
ClogP
estimates the logP of molecules
- calculated value
Groups w negative values have
increased water solubility and decreased membrane permeability
Groups w positive values (logP or ClogP)
decreased water solubility and increased membrane permeability
Pro-drugs
A pro‐drug is an INACTIVE drug that is transformed by the body into an ACTIVE drug. Usually this is used to solve a solubility or permeability issue with the
active drug
Isomers
Two compounds are isomers if they have the same molecular formula but different chemical structures
STRUCTURAL ISOMERS
Same molecular formula, but different bond
connectivity
GEOMETRIC ISOMERS
Same bond connectivity, but different arrangement about a fixed bond
STEREO‐ISOMERS
Different chirality
CONFORMATIONAL ISOMERS
Same bond connectivity, arrangement, and
chirality – but different temporal conformations.
(generally these rapidly interconvert)
R-steriochemistry
clockwise
starting Carbon molcule from the dashed wedge then go to colored in wedge
S-steriochemistry
counterclockwise
starting from the dashed wedge then go to colored in wedge
Enantiomers
have identical physical properties
- if ALL of the stereocenters are switched
Diastereomers
have similar (but different) physical properties -if SOME (but not all) of the stereocenters are switched
Note that a chiral center with a strait line
or squiggly line indicates
a mixture of stereo‐isomers
(+) compounds are
chiral molecules that rotate light clockwise
(‐) compounds are
chiral molecules that rotate light counterclockwise
(+/‐) compounds are
chiral molecules that are racemic
Epimerization
The process of converting one stereochemical center into another.
Small molecule drugs have
< 1000 Da Synthesis Pill (oral) t1/2-Hours High membrane permeability Bio target is intracellular
Large molecule drugs have
> 20000 Da Cellular expresiion taken through IV t1/2- days/weeks Low membrane perm Bio target- extracellular
Pharmacophore
The key structural components that drive binding to the biological target
-A “map” of the “core” interactions
that hold a drug in the binding site
Amines and carboxylic acids can be inserted for
two purposes
1) To form an ionic interaction with the biological target
2) To increase the solubility of the drug
How do enzymes work?
1) By increasing the “effective concentration” of reactants
2) By stabilizing the “transition state” of the intermediate
Enzymes decrease
activation energy
Antimetabolites
designed to “look” like an essential biological molecule – but cannot be processed by a normal metabolic pathway
Irreversible inhibitors (suicide inhibitors)
bind covalently to the active site of the enzyme
- Inhibitor binds
- Formation of covalent adduct
- inactivated enzyme
- enzyme is usually permanently inactivated
Competitive inhibitors sterically
block the active site of the enzyme
-closing the lid of the hopper
Potent inhibitor
a molecule that mimics intermediate
Noncompetitive inhibitors
Binding to allosteric site can activate or inhibit enzyme activity (but usually inhibits...
Proteases
cleaves an amide
Esterases
cleaves an ester
Kinases
adds a phosphate (from ATP) to Ser, Thr, or Tyr
Phosphatase
removes a phosphate from Ser, Thr, or Tyr
