QSAR Flashcards
QSAR=
quantitative structure-activity relationships
physicochemical properties of QSAR=
hydrophobicity, electronics, size
synthesize ____ analogues for SAR, synthesize _______ analogues for QSAR
15-20/ 4-5
For SAR you _______. For QSAR _______
compare IC50 values/ computer analyzes data
After SAR you synthesize _____. For QSAR you synthesize ____
new series based on results/ targeted analogues
main purpose of QSAR is
to save time due to reduced analogues synthesized and tested
QSAR method of Quantification is
linear regression analysis
y=mx+b:
y = biological activity, m = slope, x = physicochemical property, b= y-intercept
biological activity =
log (1/c) where c= compound concentration
QSAR = ____
predictive - need constant value to predict
substituent hydrophobicity constant (pi)
contribition of a given functional group to hydrophobicity relative to hydrogen
increased pi =
increased hydrophobicity and decreased water solubility
decreased pi =
decreased hydrophobicity and increased water solubility
electronics:
ionization and polarity
electronics affect
absorption and binding
hammet substituent constant (sigma)
measure of the electron donating or electron withdrawing ability of a substituent on an aromatic ring
hammet substituent constant is measured _______ based on ________
expreimentally/ difference in ionization of benzoic acid and substituted benzoic acids
positive sigma =
electron withdrawing
negative sigma =
electron donating
sigma accounts for
inductive and resonance effects
sigma sub 1
measures inductive effects (electronic effects -aliphatic)
sigma sub1 is determined _____ by ____
experimentally/ measuring the rate of hydrolysis for aliphatic esters
electron ____ groups _______ the rate of hydrolysis for aliphatic esters, making sigma sub1 negative
donating/ decrease
electron _______ groups ____ the rate of hydrolysis of aliphatic esters, making sigma sub1 positive
withdrawing/ increase
the hansch equation:
attempt to correlate biological activity to all physiochemical properties
3D QSAR considers __________ of a drug as ____
spatial orientation properties/ a whole
3D QSAR doesn’t take into account ____
conformation changes or bond rotation
If we have 4 FGs that add 0.5 each to log P, the overall P is
not assumed to be increased by 2
Comparative Molecular Field Analysis (CoMFA) builds ____
builds graphical
and statistical model correlating biological activity to changes
in steric or electronic properties of molecule.
What are the two assumptions for biological activity for 3D QSAR?
1.) overall size and shape (fit into active site). 2) electronics (binding)
CoMFA: ________ is positioned in a grid and ____ are built around it
pharmacophore/ potential analogues
CoMFA can be used in
SBDD or de novo design
values for 3D QSAR are calculated by
computer program - extensive experimental SAR not required
QSAR targets
specific analogues
Is structural knowledge of binding site required for 3D QSAR?
no
predicting active conformation of flexible compounds is ____ when using 3D QSAR
difficult
if a model is based on SAR, you must insure that all compounds bind in ______
the same orientation
4D QSAR takes into account
conformational flexibility and freedom of rotation
_________ are used to predict the best conformation of small molecules in 4D QSAR
molecular dynamics simulations
