Lecture 3 (Intro to MedChem) Flashcards Preview

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Flashcards in Lecture 3 (Intro to MedChem) Deck (51):
1

Most drugs are less than ____ Da

500

2

conformational freedom

the ability to rotate bonds freely

3

Rotatable bonds are any single bonds that are: ???

-not part of a ring
-not formed with a terminal atom
-not formed with a hydrogen atom

4

are amide C-N bonds freely rotatable?

no

5

bioavailability of ___% is considered the minimum bioavailability for the drug to be used orally

20

6

with decreasing # of rotatable bonds, the bioavailability ______

increases

7

we want delta G to be ___?

negative

8

molecules with lots of freely rotating bonds ____ delta G

increases (unfavourable)

9

What are Lipinski's Rule of Fives used to determine?

If a chemical compound can be absorbed orally
*does not dictate pharmacological activity

10

What are the Lipinski's Rule of Fives? (5)

1) molecular weight < 500
2) logP < 5
3) < 5 H-bond donors (Sum of NH and OH)
4) < 10 H-bond acceptors (Sum of N and O)
5) < 10 rotatable bonds

Note:
#5 was an additional rule added since Lipinski's original article

11

Often only one isomer will have biological activity. Why?

Because it is the only configuration that will bind to a receptor

12

In what ways can isomers differ from each other?

-different potency
-metabolized differently
-differing toxicity

13

What are the 3 types of isomers?

-constitutional (structural/positional)

-configurational

-conformational

14

Describe constitutional (structural/positional) isomers

-same atomic composition but
-different bonding arrangements between atoms

ex. catechol vs. resorcinol

15

Describe configurational isomers

-same molecular formula and the same bonds
but
-atoms are arranged differently in space with respect to each other
(think of chiral compounds ex cis/trans)

16

Two types of configurational isomers?

-optical
-geometric

17

Describe optical isomers

-mirror images
-non-superimposable
-chiral molecules
-an asymmetric carbon centre that has 4 different groups/atoms bound to it

18

optical isomers are ____

enantiomers

19

Define enantiomer

non-superimposable mirror images of each other

20

optical isomers have ___ physical and chemical properties

identical

21

Two important differences in properties between enantiomers ?

1) rotation of plane polarized light

2) interaction w chiral environments

22

Describe the rotation of plane polarized light in enantiomers

each enantiomer rotates plane polarized light to the same degree but different direction

23

dextrorotary (d) or (+)-enantiomer rotates plane polarized light which way??

to the right (clockwise)

24

levorotatory (l) or (-)-enantiomer rotates plane polarized light which way?

to the left (counterclockwise)

25

T or F: you can determine direction of rotation by looking at a compound's structure

false man
-need a polarimeter to determine direction of plane polarized light experimentally

26

What type of mixture will not rotate plane polarized light at all?

50:50 mixture (racemic mixture)

27

For 'n' asymmetric centers there are at most __ configurational isomers

2^n

28

What are diastereomers?

-compounds with more than one asymmetric centre

-not mirror images

-not superimposable

29

What are meso structures?

-two identical asymmetric centers

-mirror images

-superimposable

(these compounds are not chiral)

30

in a Fischer projection how do we orientate amino acid?

COO- is up
NH2 is down

(carboxyl group up)
(amino group down)

31

When we have the amino acid orientated in the correct way as a Fischer projection how do we determine D or L?

If the alpha hydrogen is left = L

If the alpha hydrogen is right = D

32

proteins are composed of only what type of amino acids?

L-amino acids

33

When the H's in a Fischer projection point in the same direction = ?
(for diastereomers)

erythro

34

When the H's in a Fischer projection point in opposite directions = ?
(for diastereomers)

threo

35

Describe geometric isomers

-sp2 hybridized carbon atoms of alkenes and the attached groups lie in the same plane

-rotation around double bond is restricted

36

When is it possible to have geometric isomers?

If each carbon atom in the double and has different substitutions

37

how do we differentiate between geometric isomers?

trans/cis
E/Z

38

How do you determine E or Z?

cut double bond in half

-determine if the higher priority molecules are on the same or opposite sides

39

Higher priority molecules on the same side

Z (cis)

40

Higher priority molecules on opposite sites

E (trans)

41

Describe conformational isomers (conformers)

-isomers characterized by different arrangements of atoms that result from rotation about sigma bonds

-conformers can interconvert between isomeric forms

42

Newman projections:
what conformation has a higher energy form

eclipsed

43

Newman projections:
what conformation has a lower energy form

staggered

44

bulky groups overlapping = ____ energy

highest

45

we would expect that a drug spends most of it's time in the ___ form

anti (staggered)
- this is the lowest energy form

46

6 membered ring takes one or two forms: what are the two forms

boat
chair

47

normally there is ______ _______ around sigma bonds

free rotation

48

6 membered rings are all ____ bonds

sigma

49

chair vs boat:
what is more favoured

chair
(boat causes steric interactions between hydrogens or other bulky groups which makes boat conformation unfavourable)

50

Explain boat to chair or chair to boat flipping: what happens

anything that was axial becomes equatorial

anything that was equatorial becomes axial

51

For bulky substituents the conformation that allows the substituents to be in _____ will predominate

equatorial