EXAM 4 - Organic Synthesis in Drug Development 2 Flashcards
What are good properties of a scaffold?
- flexible (bc you don’t know the active conformation yet)
- FG arms should be evenly spaced
- MW < 350
- easily prepared
What are good functional groups?
- amine
- hydroxyl
- substituted aromatic rings
- diverse
Name what functional groups are not ideal for scaffolds.
- nitrile (NO2)
- aldehydes (CHO)
Describe deconvolution.
If the first library is active –> which of the compounds are the most active –> which is the lead compound?
* identifying which specific compound of a combinatorial library is the active compound
If the screen library is tested, and all mixtures are active, then…
Test at a lower concentration.
If the screen library is tested, and some mixtures are active, then…
deconvolution to determine active compound.
If the screen library is tested, and no mixtures are active, then…
if it is first screen –> test at higher concentration
if it is not the first screen –> test another library
D) Test each mixture at 20 uM
* test mixture at a higher concentration
Explain the difference between diversity-oriented synthesis (DOS) and combinatorial chemistry.
Traditional combinatorial chemistry –> focuses on ‘drug-like’ molecules
* occupy a narrow region of “chemical space” (e.g. benzodiazepines)
* not diverse - 1000+ compounds that look the same
* if one is active… most likely a lot of them are (bc they’re so similar)
DOS –> libraries of diverse compounds that explore more “chemical space”
* tests compounds that look very different structurally
Describe chemical development.
Creating a reaction sequence to prepare up to ~1 kg of the drug.
* 1 kg is used for .. initial preclinical testing, toxicity studies and formulation
Describe chemical development.
Creating a reaction sequence to prepare up to ~1 kg of the drug.
* 1 kg is used for .. initial preclinical testing, toxicity studies and formulation
Describe process development.
Reworking of the synthetic route to produce ton quantities of the drug with consistent yield and purity.
* greater than 1 kg
* reduce number of steps
* reduce need for purification at each step
* consistent production of drug
Describe process development.
Reworking of the synthetic route to produce ton quantities of the drug with consistent yield and purity. (make a lot of drug) z
* greater than 1 kg
* reduce number of steps
* reduce need for purification at each step
* consistent production of drug
B) To synthesize compounds that occupy a wider range of chemical space.
B) To synthesize compounds that occupy a wider range of chemical space.
