QSAR Flashcards Preview

Fundamentals of Bio Orgo > QSAR > Flashcards

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

10

QSAR = ____

predictive - need constant value to predict

11

substituent hydrophobicity constant (pi)

contribition of a given functional group to hydrophobicity relative to hydrogen

12

increased pi =

increased hydrophobicity and decreased water solubility

13

decreased pi =

decreased hydrophobicity and increased water solubility

14

electronics:

ionization and polarity

15

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

19

negative sigma =

electron donating

20

sigma accounts for

inductive and resonance effects

21

sigma sub 1

measures inductive effects (electronic effects -aliphatic)

22

sigma sub1 is determined _____ by ____

experimentally/ measuring the rate of hydrolysis for aliphatic esters

23

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

_________ are used to predict the best conformation of small molecules in 4D QSAR

molecular dynamics simulations