Brainscape's Knowledge GenomeTM

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


See full index

PY366 Drug discovery > Sources of new drugs > Flashcards

Sources of new drugs Flashcards

1
Q

what is lead discovery

A

the process of identifying active new chemical entities, which by subsequent modification may be transformed into a clinically useful drug

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

what is lead generation

A

strategies developed to identify compounds which possess a desired but non optimised biological activity

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

what may be the disadvantages of lead activity molecules

A
  1. may be peptidic
    - poorly absorbed
    - rapidly cleared
  2. may have poor drug like properties and poor pharmacokinetics profile
  3. final drug may only be barely similar to original substance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are the strategies for discovery of lead activity molecules

A
  1. exploitation of biological information
  2. improvement of existing drugs
  3. systematic screening
  4. planned research and rational drug design
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what does exploitation of biological information involve

A
  1. study of natural products
  2. study of indigenous medicines (ethnopharmacology)
  3. clinical observation of side effects of medicines
  4. observations made in other scientific studies- animals and plants
  5. activities of industrial chemical products
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what are natural products known as

A
  1. medicines- opium, atropine, cocaine (local anaesthetic)
  2. toxins and poisons- snakes, scorpions
  3. hallucinogens- alcohol, atropine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

why were sympathomimetics discovered

A

a shortage of the drug ephedrine led to the development of amphetamines and other sympathomimetics

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

what is bothrops jararaca

A
  • brazilian pit viper
  • venom contains peptides
  • known to be ACE inhibitors and bradykinin potentiators
  • pro containing dipeptide inhibitors worked best in vivo
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what does ethnopharmacology involve

A
  1. neuromuscular blocking agents
    - atracurium
    - artemisinin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what is artemisinin used for

A
  • active substance in TCM
  • used for chloroquine resistant malaria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are the properties of procaine

A
  • rapidly metabolised
  • has CNS side effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what are the properties of procainamide

A
  • resistant to esterases
  • less lipid soluble
  • fewer CNS side effects
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what are the properties of metoclopramide

A
  • effective antiemetic
  • high doses can give dystonic reactions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the properties of chlorpromazine

A
  • antipsychotic
  • also antiemetic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what are the properties of sulpiride

A
  • effective antipsychotic agent
  • lacks the sedating properties of chlorpromazine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

give examples of observations made in other scientific studies

A
  • anticancer alkaloids from catharanthus roseus tested for antidiabetic activity
  • rats used died of septicaemia due to leukopenia
  • vincristine, vinblastine identified as potent anti leukaemia drugs
17
Q

give examples of activities of industrial chemical products

A

nitroglycerin gave workers headaches
- potent vasodilator
- isosorbide mononitrate and isosorbide dinitrate used in treatment of angina

18
Q

what is involved in improving existing drugs

A
  1. seek to achieve improved
    - potency
    - selectivity
    - safety
    - duration of action
    - formulation more easily handled by healthcare staff or more acceptable to patient
  2. competing with market leader may be financially advantageous
    - target is already defined
    - market is already established
    - clinical trials have good reference point
19
Q

describe how B lactams were improved

A
  • penicili=lins
  • side chain modifications and b lactam cycle modifications
  • allows for different selectivity of activity
20
Q

describe how H2 blockers were improved

A
  • ranitidine became market leader
  • cimetidine inhibits CP450
21
Q

describe how ‘consoles were improved

A
  • fungistatics inhibit ergosterol biosynthesis
  • fluconazole is safe via oral route
22
Q

what is involved in systematic screening

A
  1. seek to test as many different compounds as possible
  2. sources of test compounds
    - natural products
    - chemical libraries
  3. need assay systems that are fast and reliable
23
Q

give examples of drugs derived from screening dyes

A
  1. chloroquine- antimalarial
  2. trypanosomiasis- sleeping sickness in Africa
  3. bendroflumethiazide and furosemide- diuretics
  4. benzodiazepines- anxiolytics and hypnotics
24
Q

what is high throughput screening

A

screen a large number of small molecule compounds for interaction with the target system
- hope to find at least one hit on the target system

25
Q

what are the advantages of high throughput screening

A
  1. assay system is immobilised
  2. many replicates in well plates
  3. highly automated
    - liquid handling
    - detection of response
    - presentation and analysis of data
  4. very large automated robotic systems
  5. capable of screening millions of samples per day
26
Q

what is combinatorial synthesis

A

a process to prepare large sets of organic compounds by combining sets of building blocks

27
Q

what is the goal of creating molecular libraries

A

to synthesise and test as many molecules as possible in as few as possible steps
- an attempt to produce very large libraries for screening

28
Q

what are the problems with combinatorial chemistry

A
  1. working out what you have in the library
  2. working out which molecules are active- testing many molecules
  3. low hit rates
  4. high costs
  5. low quality hits
    - poor bioavailability
    - toxicity
  6. chemically reactive, false positives
  7. problems with the chemistry
    - individual chemical reactions shouldn’t yield alternative products
    - should be high yielding at each step
29
Q

give examples of successes from high throughput screening/combinatorial chemistry

A
  1. insulin mimetics
  2. thrombin inhibitors
  3. selective COX 2 inhibitors
30
Q

what is fragment based lead discovery

A
  1. libraries of fragments of drug molecules are screened
    - RMM <300
    - logP <3
    - hydrogen bond donors and acceptors <3
  2. fragments that show binding to a target are selected for further development
    - usually low affinity
    - multiple fragments can be combined
  3. better success rate than combinatorial chemistry
31
Q

what is involved in planned research and rational drug design

A
  1. identify a target or biochemical system
  2. attempt to address the target/system directly
  3. use endogenous molecules as a starting point (lead)
32
Q

give examples of antimetabolites

A

molecules that are dihydrofolate reductase inhibitors
- trimethoprim- antibacterial
- 6-mercaptopurine- anticancer
- azathioprine- immunosuppressant

33
Q

describe the difference between cortisol and prednisolone

A

prednisolone has increased glucocorticoid activity and reduced mineralocorticoid activity compared to cortisol

34
Q

what are endogenous biochemicals

A
  • manipulating the structure of an endogenous molecule could give drugs with improved performance
  • preparing mimics of endogenous molecules can be used to disrupt physiological processes
  • b blockers
  • H2 antagonists
  • ACE inhibitors
35
Q

is a lead activity molecule beneficial

A

has little use
- needs to be transformed into a new chemical entity

36
Q

what are the advantages of new chemical entities

A

molecules by design typically have better
1. pharmacodynamic properties- better selectivity/potency
2. pharmacokinetic properties- ADME
3. physicochemical properties- stability, formulation
4. toxicological properties
5. patentability- opportunity to recover development costs

PY366 Drug discovery (15 decks)

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