Medicinal Chemistry Exam #3 Test
Bank Questions With 100% Correct
Solutions.
Structure-activity relationships (SAR) - Answer define the functional groups or regions of a
lead compound which are important to its biological activity. Can alter, remove, or mask a
functional group then test the analogue for activity
Alcohols - Answer H-bond acceptor/donor; an ether analogue would inhibit HBD and HBA as
steric shield
Amines - Answer ionic and H-bond donor and/or acceptor (tertiary amines only HBA's not
HBD); 2° and 3° amide analogues cannot ionize = no ionic bonding, also poor HBA; acyl groups
can produce steric effects hindering HBD
Quaternary ammonium salts - Answer ionic bonding and induced dipole interactions;
amine/amide analogues
Ketones and aldehydes - Answer dipole-dipole interactions and HBA; 2° alcohol analogues
change stereochemistry from planar to tetrahedral and may move oxygen out of range
Esters, HBA by either oxygen - Answer reduction to alcohols remove carboxylic groups and can
establish importance of carbonyl oxygen
Amides, carbonyl group acts as HBA - Answer 1° and 2° amides HBDs; 3° amides unable to act
as HBD; reduction to amine removes carbonyl group and can establish importance of O; N-
methylation prevents HBD interactions and can produce steric effects
Carboxylic acids - Answer can interact by ionic and H-bonding (both) at the same time;
reduction removes carbonyl oxygen as HBA and inhibits ionization; esterification prevents
ionization, HBD interactions, and can hinder HBA by steric effect
Aromatic rings and alkenes - Answer can interact via VDW in hydrophobic regions; analogues
may not fit
, In vivo tests - Answer are for pharmacological activity
Pharmacophore - Answer summarizes the important binding groups that are required for
activity on the targets, and their relative positions in space with respect to each other; 2D
defines the minimum skeleton connecting important binding groups, 3D defines relative
positions in space.
The active conformation - Answer is the conformation adopted by a drug when it binds to its
target and produces the desired effect. Elucidation by x-ray crystallography or NMR.
Vary alkyl substituents - Answer vary length and bulk of group to optimize interaction &
introduce selectivity to modify hydrophobic activity
Vary aryl substituents - Answer vary groups or patterns (ortho, meta, para)
Extension (add extra functional groups) - Answer explore target binding site for further binding
regions to achieve additional binding interactions
Chain extension/contraction - Answer vary length of chain if a chain is present in connecting 2
binding groups
Ring expansion/contraction - Answer improves overlap of binding groups w/their binding
regions
Ring variations - Answer sometimes results in improved properties by differing heteroatoms
Isosteres and bio-isoteres - Answer are atoms or groups of atoms which share the same
valency and which have chemical or physical similarity; replacing a group with its isostere to
obtain alteration in size/electric, electronic property, hydrophobicity, or polarity
Bioisosteres - Answer are more broadly defined, concerning a group that can be used to
replace another group while retaining the same biological activity. These include both classical
and non-classical isosteres.
Bank Questions With 100% Correct
Solutions.
Structure-activity relationships (SAR) - Answer define the functional groups or regions of a
lead compound which are important to its biological activity. Can alter, remove, or mask a
functional group then test the analogue for activity
Alcohols - Answer H-bond acceptor/donor; an ether analogue would inhibit HBD and HBA as
steric shield
Amines - Answer ionic and H-bond donor and/or acceptor (tertiary amines only HBA's not
HBD); 2° and 3° amide analogues cannot ionize = no ionic bonding, also poor HBA; acyl groups
can produce steric effects hindering HBD
Quaternary ammonium salts - Answer ionic bonding and induced dipole interactions;
amine/amide analogues
Ketones and aldehydes - Answer dipole-dipole interactions and HBA; 2° alcohol analogues
change stereochemistry from planar to tetrahedral and may move oxygen out of range
Esters, HBA by either oxygen - Answer reduction to alcohols remove carboxylic groups and can
establish importance of carbonyl oxygen
Amides, carbonyl group acts as HBA - Answer 1° and 2° amides HBDs; 3° amides unable to act
as HBD; reduction to amine removes carbonyl group and can establish importance of O; N-
methylation prevents HBD interactions and can produce steric effects
Carboxylic acids - Answer can interact by ionic and H-bonding (both) at the same time;
reduction removes carbonyl oxygen as HBA and inhibits ionization; esterification prevents
ionization, HBD interactions, and can hinder HBA by steric effect
Aromatic rings and alkenes - Answer can interact via VDW in hydrophobic regions; analogues
may not fit
, In vivo tests - Answer are for pharmacological activity
Pharmacophore - Answer summarizes the important binding groups that are required for
activity on the targets, and their relative positions in space with respect to each other; 2D
defines the minimum skeleton connecting important binding groups, 3D defines relative
positions in space.
The active conformation - Answer is the conformation adopted by a drug when it binds to its
target and produces the desired effect. Elucidation by x-ray crystallography or NMR.
Vary alkyl substituents - Answer vary length and bulk of group to optimize interaction &
introduce selectivity to modify hydrophobic activity
Vary aryl substituents - Answer vary groups or patterns (ortho, meta, para)
Extension (add extra functional groups) - Answer explore target binding site for further binding
regions to achieve additional binding interactions
Chain extension/contraction - Answer vary length of chain if a chain is present in connecting 2
binding groups
Ring expansion/contraction - Answer improves overlap of binding groups w/their binding
regions
Ring variations - Answer sometimes results in improved properties by differing heteroatoms
Isosteres and bio-isoteres - Answer are atoms or groups of atoms which share the same
valency and which have chemical or physical similarity; replacing a group with its isostere to
obtain alteration in size/electric, electronic property, hydrophobicity, or polarity
Bioisosteres - Answer are more broadly defined, concerning a group that can be used to
replace another group while retaining the same biological activity. These include both classical
and non-classical isosteres.
