Flashcards in QSAR Deck (39):
1
QSAR=
quantitative structure-activity relationships
2
physicochemical properties of QSAR=
hydrophobicity, electronics, size
3
synthesize ____ analogues for SAR, synthesize _______ analogues for QSAR
15-20/ 4-5
4
For SAR you _______. For QSAR _______
compare IC50 values/ computer analyzes data
5
After SAR you synthesize _____. For QSAR you synthesize ____
new series based on results/ targeted analogues
6
main purpose of QSAR is
to save time due to reduced analogues synthesized and tested
7
QSAR method of Quantification is
linear regression analysis
8
y=mx+b:
y = biological activity, m = slope, x = physicochemical property, b= y-intercept
9
biological activity =
log (1/c) where c= compound concentration
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QSAR = ____
predictive - need constant value to predict
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substituent hydrophobicity constant (pi)
contribition of a given functional group to hydrophobicity relative to hydrogen
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increased pi =
increased hydrophobicity and decreased water solubility
13
decreased pi =
decreased hydrophobicity and increased water solubility
14
electronics:
ionization and polarity
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electronics affect
absorption and binding
16
hammet substituent constant (sigma)
measure of the electron donating or electron withdrawing ability of a substituent on an aromatic ring
17
hammet substituent constant is measured _______ based on ________
expreimentally/ difference in ionization of benzoic acid and substituted benzoic acids
18
positive sigma =
electron withdrawing
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negative sigma =
electron donating
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sigma accounts for
inductive and resonance effects
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sigma sub 1
measures inductive effects (electronic effects -aliphatic)
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sigma sub1 is determined _____ by ____
experimentally/ measuring the rate of hydrolysis for aliphatic esters
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electron ____ groups _______ the rate of hydrolysis for aliphatic esters, making sigma sub1 negative
donating/ decrease
24
electron _______ groups ____ the rate of hydrolysis of aliphatic esters, making sigma sub1 positive
withdrawing/ increase
25
the hansch equation:
attempt to correlate biological activity to all physiochemical properties
26
3D QSAR considers __________ of a drug as ____
spatial orientation properties/ a whole
27
3D QSAR doesn't take into account ____
conformation changes or bond rotation
28
If we have 4 FGs that add 0.5 each to log P, the overall P is
not assumed to be increased by 2
29
Comparative Molecular Field Analysis (CoMFA) builds ____
builds graphical
and statistical model correlating biological activity to changes
in steric or electronic properties of molecule.
30
What are the two assumptions for biological activity for 3D QSAR?
1.) overall size and shape (fit into active site). 2) electronics (binding)
31
CoMFA: ________ is positioned in a grid and ____ are built around it
pharmacophore/ potential analogues
32
CoMFA can be used in
SBDD or de novo design
33
values for 3D QSAR are calculated by
computer program - extensive experimental SAR not required
34
QSAR targets
specific analogues
35
Is structural knowledge of binding site required for 3D QSAR?
no
36
predicting active conformation of flexible compounds is ____ when using 3D QSAR
difficult
37
if a model is based on SAR, you must insure that all compounds bind in ______
the same orientation
38
4D QSAR takes into account
conformational flexibility and freedom of rotation
39