Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Med Chem 9 > Opioids > Flashcards

Opioids Flashcards

You may prefer our related Brainscape-certified flashcards:
Periodic Table flashcards Chemistry 101 flashcards AP® Chemistry flashcards Organic Chemistry 101 flashcards
1
Q

What are the 2 classes of alkaloids?

A

Phenanthrene alkaloids

Benzyl isoquinoline alkaloids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What drugs are phenanthrene alkaloids?

A

Morphine

Codeine (prodrug)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What drugs are benzyl isoquinoline alkaloids?

A

Papaverine

Noscapine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which of the 2 classes have analgeic effects?

A

Phenanthrene alkaloids only

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is a prodrug?

A

Administered in an inactive or less than fully active form that is through a metabolic process

typically hydrolysis of an ester via esterase activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

We use prodrugs to improve what?

A

ADME

Bioavailability

Side effects profile

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which drugs mentioned in lecture are prodrugs?

A

heroin

codeine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How can you increase activity of morphine?

A
  1. add alkyl group on C17 (longer than ethyl, no longer than 6C)
  2. add phenethyl > activity than benzene ring
  3. saturated double bond between C7 and C8
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How can you modify morphine to reduce toxicty while retaining analgesic effects?

A

Add acetyl group to C6 (instread of OH)

Epimerize C6 OH from a to B

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does heroin’s structure differ from morphine?

A

acetyl groups instead of OH at C3 and C6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

T/f codeine is more active than morphine

A

false!

Codeine is less active due to methoxy group on C3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Difference between OH at C3 vs C6

A

OH at 3: attached to phenyl group, more acidic, better leaving group = faster hydrolysis

OH at 6: attached to alkyl group

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the chiral centers located in morphine?

A

5Ra

6Sa

9R

13S

14R

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How are the morphine rings fused together?

A

B/C: cis

C/D: trans, C built off equatorial bonds of D

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the class of flexible opioids?

A

Phenylpiperidine carboxylate class

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

When do flexible opioids have optimal activity?

A

methyl group on position 1 (N atom)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How are prodine and meperidine different structurally?

A

Prodine: contains methyl to C4 and reverse ester

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Features of acyclic analgesic vs morphine

A

tolerance develops more slowly

less euphoria + less withdrawal

highly flexible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the best method of fragment based med chem?

A

NMR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe fragment based drug design

A

Find a lead fragment via NMR

Optimize fragment by adding groups to it to find what increases or decreases activity to discover new drug compopunds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How do we measure the probability of an effective drug compound?

A

using heavy atom count and free bond energy to calculate ligand efficiency (LE)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What is a pharmacophore?

A

Abstract description of molecular features of a compound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Why are pharmacophores used in drug discovery?

A

Used to show how structurally diverse compounds can bind to the same receptor/enzyme

  • show minimum structure required for ligand receptor/enzyme recognition
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the pharmacophore features of morphine like derivatives?

A
  1. hydrophobic region
  2. aromatic rings
  3. H donor/acceptors
  4. cations and anions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What does a 2D pharmacophore represent?

A

Minimum skeletal connecting important binding groups of the compounds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Does the 2D pharmacophore provide analgesic effects?

A

no!

requires stereochemical conformation with limited bond rotation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What does a 3D pharmacophore represent?

A

Define relative positions in space of the important binding groups

  • gives opiates their analgesic activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What are the endogenous opioids?

A
  1. Enkephalin
  2. B-endorphin
  3. Dynorphins
  4. Endomorphans
29
Q

What are the 2 types of enkephalin?

A

Met

Leu

30
Q

What type of receptors are opioid receptors?

A

GPCRs

31
Q

List the opioid receptors

A

Mu

Kappa

Delta

NOP

32
Q

Kappa receptors

A

spinal analgesia

sedation

anesthesia

33
Q

Mu receptors

A

Supra spinal analgesia

Euophria/feelings of well being

Morphine type physical dependence and withdrawal

34
Q

Delta receptors

A

Supra spinal analgesia

More side effects of tolerance and euphoria

35
Q

NOP receptors

A

do NOT bind classical opioid peptides/non-peptide agonists with high affinity

36
Q

Pure agonists

A

potent analgesic and morphine like side effects

tolerance

dependence

respiratory depression

37
Q

Partial agonist

A

potent analgesic activity with decreased morphine like side effects

38
Q

Pure antagonist

A

No analgesic effects

no morphine side effects

used to reverse actions of morphine like activity

39
Q

How can you decrease activity of mu receptor agonists?

A

Position 3

remove OH, add H

substitute methoxy for OH

substitiute methyl ester

40
Q

How can you increase the activity of mu receptor agonists?

A

Position 6:

substitute H for OH

convert OH to ketone AND add 2 OH at C7 and C8

substitute ester for OH

Position 14: add b-OH

Position 7 and 8: add di-hydro goups

change methyl N to phenethyl N

41
Q

How does the structure of morphinan differ from morphine?

A

Only 3 chiral centers: 9R, 13S, 14R

No E ring and no OH on phenyl group

No OH at C6 or double bond between C7 and C8

42
Q

SAR of morphinans

A

similar as morphine

isomers: - levo = more potent than morphine

+ dextro = no opioid activity but good antitussive activity

trans B/C rings = more potent analgesic

43
Q

How does the structure of butorphanols differ from morphine?

A

No E ring

3 chiral centers (9R, 13S, 14R)

b-OH at C14

cyclobutylmethyl ring off of carbon attached to N

44
Q

SAR and activity of butorphanol

A

5x more potent as analgesic

behaves as both weak mu antagonist and strong k agonist

45
Q

How does benzomorphan differ from morphine?

A

No E or C rings

46
Q

Which sterochemical configuration of benzomorphans is more potent?

A

Beta: B/C trans

47
Q

Which group can increase analgesic activity of benzomorphans?

A

CH2-CH2-phenyl group

48
Q

Which R groups change the activity to partial agonist or antagonist of benzomorphans?

A

cyclopropylmethyl

CH2CH = CH2

49
Q

What R group requirements to retain activity of benzomorphans?

A
  1. contain non-H substitutents
  2. lower MW alkyl groups: not larger than propyl
  3. can be a phenyl group
50
Q

The 3 position in phenylpiperidines is related to which position in morphine and benzomorphan?

A

Morphine = C14

Benzomorphan = C9 (C11 of benzazocine)

51
Q

Is the alpha or beta position of prodine more potent?

A

Beta: 3S, 4S (cis)

52
Q

Which position of prodine relates to morphines C14?

A

3

53
Q

Circle the compound structure modifications that increase potency of meperidine

A
54
Q

How can you change activity from agonist to angtagonist?

A

N atom: substitute NCH2CH=CH2 for methyl

Reduce C7=C8 to single bond with di-hydros

position 6: convert OH to ketone

B-OH at C14

55
Q

Which N is most basic?

A
56
Q

Which CYPs dealkylate methadone?

A

CYP2C19: R isomer (active)

CYP2B6: S isomer (inactive)

57
Q

What 3 active metabolites are produced from methadone?

A

methadol

normethadone

dinormethadol

58
Q

How is methadone get to methadol?

A

Reduced (removal of carbonyl)

CYP dealkylated further to normethadol

Normethadol = CYP dealkylated to dino

59
Q

How does methadone get to normethadone?

A

CYP dealkylation

One methyl on N compared to 2 with methadone

further dealkylated to dino (2H on N)

60
Q

How do we activate the prodrug codeine?

A

O demethylation which converts it to morphine

61
Q

What process inactivates codeine to norcondeine?

A

N demethylation (no methyl group on N)

62
Q

What happens if you continue to demethylate norcodeine?

A

Can produce an active metabolite: O methylation occurs to expose 3OH (normorphine)

63
Q

Which positions are subject to phase II reactions? What are the reactions?

A

Phenolic 3OH and alcoholic 6OH

subject glucuronidation and sulfation

64
Q

Metabolism to activate heroin

A
  1. hydrolysis of 3 position acetyl group to OH (will occur fast)
  2. hydrolysis of 6 position acetyl group with occur more slowly than 3
65
Q

Non-selective reaction involves what?

A

N in b-CNA forming a 3 member ring, expelling Cl

66
Q

Non-selective b-CNA

A
  • Nu from receptor wil lthen attack 3 member ring to open and create covalent bond
  • this repeats due to 2 Cl side chaines on amine at C6
67
Q

slective b-FNA reaction involves what?

A

Lys N attacking double bond of R group

Form zwitterion intermediate that then results in covalent bond

68
Q

What makes an ideal opioid drug?

A
  1. orally active drug with strong analgesic properties
  2. does not cause: tolerance, physical dependence, respiratory depression, emesis

Med Chem 9 (1 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions