Functional Group Charactristics and Roles Flashcards
Functional group
structural component of a drug molecule with one or more atoms
Which properties do functional groups influence?
solubility
route of admin
ability of drug to bind to its target
mechanism of action
route of metabolism and elimination
duration of action
suitability for specific use
tendency to cause ADRs or drug interactions
You can alter functional groups to ?
enhance activity
increase absorption
decrease adverse effects
provide therapeutic benefits
What does SAR stand for?
structure activity relationship
What are the 3 chemical effects that functional groups have?
electronic
solubility
steric
Is it possible to change just one of the chemical properties of a functional group?
no
What do effects of a functional group depend on?
the environment surrounding it
electronic effect
ability to donate or withdraw electrons from adjacent atoms or functional groups
Resonance
when electrons are shared among a group of atoms that have adjacent double bonds and lone pairs of electrons
Intrinsic Inductive Effect
ability of atom/functional group to attract electrons towards itself and away from other atoms/functional groups
A higher electronegativity indicates?
a greater ability to attract electrons
Oxygen inductively attracts electrons from all other atoms except for?
F
Oxygen, nitrogen, and all 4 halogens will inductively attract electrons from?
carbon and hydrogen
What are some examples of electron donating functional groups?
aromatic hydroxyl
aromatic ether
aromatic amine
aromatic thiol
ionized acidic group
alkyl group
Negatively charged functional groups can donate electrons through ?
induction
Nucleophilic functional groups contain ?
either a negative charge or a lone pair of electrons
Examples of electron withdrawing groups
halogens
trifluoromethyl
ionized basic group
hydroxyl
sulfhydryl or thiol
ether
nitrile group
nitro group
aromatic heterocyclic
aldehyde
amide
ester
sulfonamide
When hydroxyl, sulfhydryl, and ether groups are not adjacent to either an aromatic ring or double bond system they will act as?
electron withdrawing groups
Electrophilic functional groups contain?
positive charges, a conjugated double bond system, or a good leaving group
Overall water/lipid solubility of drug molecule is equal to ?
the sum of the contributions of each functional group
What properties contribute to water solubility of functional groups?
ability to ionize and form hydrogen bonds
Ionization xxx the water solubility of a drug
increases
Examples of acidic functional groups
carboxylic acid
beta-dicarbonyl
imide
sulfonamide
sulfonylurea
phenol
sulfonic acid
phosphonic acid
Examples of basic functional groups
primary, secondary, and tertiary aliphatic amines
alicyclic amine
imine
amidine
guanidine
hydrazine
primary aromatic amine
heterocyclic nitrogen (imidazole)
heterocyclic nitrogen (quinoline)
Which atom can serve as a bridge between electronegative atoms?
hydrogen
Examples of hydrogen bond acceptors only
ketone
ester
thioether
heterocyclic nitrogens- 6 membered
fluorine
ether
Examples of hydrogen bond donors only
heterocyclic nitrogen - 5 membered
Examples of hydrogen bond acceptors and donors
phenol
amide
primary, secondary, and tertiary hydroxyls
thiol
carbamate
urea
primary and secondary unionized amines
unionized carboxylic acids
Lipid solubility functional groups lack the ability to
either ionize or form hydrogen bonds
Examples of lipid soluble functional groups
aromatic rings and ring systems
alkyl chains
alicyclic rings
alkenes
alkynes
halogens
Which functional group can be viewed as either water or lipid soluble based on the groups attached to them?
Esters
Can 2 atoms/functional groups occupy the same space?
no
Steric effects contribute to the xxx of the drug molecule.
shape
What of each functional group must be able to be accommodated for by receptor binding sites?
size and shape
What are some results of steric effects?
increased selectivity
enhanced binding
alteration of metabolism
The same functional groups can provide xxx effects on different drug molecules
different
Can a single functional group serve more than one purpose?
yes
What is an isostere?
group of molecules or ions that have the same number of valence electrons and have chemical or physical similarities
Monovalent isosteres
CH3
NH2
OH
F
Cl
SH
Br
I
Bivalents Isosteres
-CH2-
-O-
-NH-
-S-
-CH2-r-CH2
Trivalent Isosteres
-CH=
-N=
-P=
-CH2-R=CH
Annular Equivalent Isosteres
aromatic ring systems
-CH=CH-
-NH-
-O-
-S-
Advantages of Isosteres
decreased metabolism; enhanced duration; allows oral use
increased bioavailability
conversion of metabolites to antimetabolites
development of antagonists/inhibitors from agonists/ substrates
enhanced solubility
increased receptor binding
separate activities
me-too drugs
