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Flashcards in QSAR Deck (23)
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1
Q

what is De Novo drug design and what two things are used to help with drug design?

A
  • it a design requiring knowledge of potential drug target

- uses QSAR and molecular modelling to help design the drug.

2
Q

what are molecular descriptors?

A
  • hydrophobicity
  • steric bulk
  • electronic effect
3
Q

what interactions do drug and targets have?

A
  1. covalent
  2. hydrophobic
  3. van der Waals
  4. H-bonds
  5. electrostatic
  6. pi-stacking
  7. combinations
4
Q

what is QSAR?

A

the relation of the biological activity of a series of compounds to their physicochemical parameters in a quantitative fashion using a mathematical formula.

5
Q

what are the common physicochemical properties of drugs?

A
  1. hydrophobicity of a molecules
  2. hydrophobicity of substituents
  3. electronic properties of substituents
  4. steric properties of substituents
6
Q

what factors increase drug binding?

A
  1. increased logP

2. greater hydrophobicity

7
Q

what logP value causes molecule to enter the CNS?

A

2.3

8
Q

why do we alter logP values of drugs away from 2.0?

A

because drugs with loP of around 2.3 can enter the CNS easily. So altering logP reduces the CNS side effects of the drug.

9
Q

what is the substituent hydrophobicity constant?

A
  • a measure of the substituents hydrophobicity relative to hydrogen.
  • identifies substituents that might interact with hydrophobic regions in binding site
10
Q

what does a positive and negative hydrophobicity constant value mean?

A

positive: substituents are more hydrophobic than H
Negative: substituents are less hydrophobic than H

11
Q

when the substituent is an electron withdrawing group, is the hammett constant positive or negative?

A

hammett constant is positive

12
Q

when the substituent is an electron donating group, is the hammett constant positive or negative?

A

hammett constant is negative

13
Q

what does molar refractivity measure?

A

the effective volume of substituents

14
Q

What two things does a QSAR equation relate together?

A

the physicochemical properties to the biological activity of a series of compounds

15
Q

what three factors are included in a QSAR equation?

A
  1. LogP
  2. Hammett Substituent Constant
  3. Molar Refractivity
16
Q

what happens to the activity of a drug if it has a positive hydrophobic substituent constant?

A

activity increases

17
Q

what happens to the activity if a drug is it has a negative hammett substituent constant?

A

activity increases

18
Q

three factors that increase drug activity?

A
  1. an increase in logP (so more hydrophobicity)

2. negative hammett substituent values (i.e. electron donating substituents)

19
Q

what is the craig plot useful for?

A
  • allows an easy identification of suitable substituents for a QSAR analysis including both relevant properties (hammett and logP)
  • so you pick a subsituent from different parts of the quadrat to ensure orthogonality (variation).
20
Q

what two substituent selection processes are available?

A
  1. craig plot

2. topliss tree

21
Q

what is a pro of using the topliss decision tree?

A

-it aids you to think about the substituent parameters and put them in order.

22
Q

what are bioisosteres?

A

substituents with comparative physicochemical properties

23
Q

what us free-Wilson QSAR?

A

a measure of the biological activity of the parent structure and comparing this with the activity of analogues bearing different substituents

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