Exam #1 Flashcards
What is Medicinal Chemistry?
The chemistry of drugs and their targets
-Discovery
-synthesis
-mechanism
-Stability and metabolism
John Proctor-Fr of Pharmacy
What is the relevance to pharmacy?
- foundational scientific knowledge: the chemistry of how drugs work.
- increasing importance in personalized medicine (if people carry mutations)
- inform therapeutic evaluations, recommendations, patient counseling for safe and effective use of drugs.
- clinical experts
Where do drugs come from?
Natural products
Rational Design
-Ligand-based drug design
-Structure based drug discovery
High-throughput Screening
-chemically diverse libraries
-fragment-based drug design
-computational screening
Natural Products
Plants/ microbes/ animals
Ligand based
Takes drug and target and creates drug target complex, that creates a physiological effect.
-focuses on the ligand: which part of the ligand improves binding to the target without having to know anything about target
ex: finding out if you have a right or left-handed glove by seeing which hand fits into it
Structure based
Based on structure of the target
ex: looking at glove and seeing that right or left hand goes in
Screening
Testing a large number of structurally diverse chemical compounds in a rapid manner to find compounds that bind to the target or have other properties.
-testing for binding/ inhibition effects
Mechanism of how drugs work
kd= (target)(drug)/ (target:drug)
the lower the kd the tighter bond it has to the target; higher drug affinity.
the more negative the Delta G= the more favorable/ strong it binds to the target.
The lower the IC the more potent
-The lower the IC, the lower the Kd
the lower the Emax the less effective
Structure-Activity Relationships (SAR)
Changes in chemical structure impact biological activity
-SAR: Structural activity relationship: enables the improvement to make drugs that bind more potently and selectively to targets.
ADME-Tox
A: Absorption-movement of drug into the bloodstream
D: Distribution- reversible transfer of drug from one location to another in the body
M:Modification- biochemical modification of drug structure, usually by enzymes
E: excretion- elimination of drugs and their metabolites from the body
Tox: Toxicity: damage to the body caused by the drug
Molecule Depictions
Molecular: C3H10
Structural: CH3(CH2)2 CH3
Bond-line drawing
line drawing
Combination
Typical bonding patterns for
H
O
N
C
Halogens
P
S
H=1
O=2 bonds; 3 bonds it is +
N=3; 4 bonds it is +
C=4
Halogens=1
P=3 or 5
S=2, 4 or 6; 3 bonds it is +
Tautomerization
Atom connectivity is different (if you lose or add an H)
-Need to use equilibrium arrows ( two arrows)
-Each structure represents a different species in equilibrium with. The other.
Resonance
-Atom connectivity does not change
-not separate species, the molecule is a combination of all the resonance forms.
-use resonance arrow ( double-sided arrow)
Partial charges
-suggest where a reaction can occur(where a nucleophile can attack)
-relevant for drug stability, metabolism and sometimes mode of action.
