EXAM 4 - Organic Synthesis in Drug Development Flashcards

1
Q
A

D) combinatorial synthesis

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2
Q

What is the goal of linear, convergent, and parallel synthesis?

A

Goal: Make one compound/set of 10 compounds to study SAR and make sure the quality of the compounds are very good.
(quality over quantity)
* used to make small set of targeted analogues

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3
Q

What is the goal of combinatorial chemistry?

A

Goal: make as many compounds as possible as fast as possible
* tested as mixture of compounds or as single compound (HTS)
* make 5000 compounds with the same scaffold (very similar structure)

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4
Q

What is the goal of diversity-oriented synthesis?

A

Goal: produce as many diverse compounds as possible from a single scaffold
* make 30 compounds that are diverse –> will tell you what structure you might need for your active compound

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5
Q

What is the difference between linear+convergent synthesis and parallel synthesis?

A

Linear + convergent synthesis - describe approaches to a sequence of organic reactions
* almost always multiple reactions

Parallel synthesis - describes approach for 1 reaction

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6
Q

Explain what overall yield is.

A

How much of desired end product obtained based on original starting material.

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7
Q

Describe the process of linear synthesis.

A

Linear - sequential reactions in which product of first reaction is used in the next reaction in a linear fashion.

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8
Q

Describe the process of convergent synthesis.

A

Fragments are synthesized before coupling them together in final reaction
* designed to improve overall yield of final compound
* decrease time bc you can create seperate parts of the compound at the same time then couple them together

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9
Q

Describe the process of parallel synthesis.

A

Performing organic reactions “side-by-side” to generate diverse compounds for SAR.
* using the same intermediate that reactions with a different molecule = diverse products/compounds
* modifications made to lead to create diversity should be done at last possible step.

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10
Q

What is the importance of building in diversity at the end of synthetic sequence?

A

Less reactions required = save time, money, and reagents

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11
Q

Of the three techniques, which is used most often?

A

Most times, all three of the techniques will have to be used to generate SAR to optimize different regions of the lead.
* techniques are not mutually exclusive

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12
Q

What is the ideal number of reactions to generate compounds for SAR?

A

Less than 5 is ideal
Greater than 10 is okay, not ideal

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13
Q

What is the best time to add diversity to the compounds?

A

At the latest possible step
* will save time and money
* early reactions will occur at “large-scale”

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14
Q
A

A) Utilizing a convergent approach increases the overall yield
* also saves time/money

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15
Q

Describe how combinatorial chemistry works.

A
  • a particular set of building blocks/precursors are used to prepare all possible derivatives of a given compound class.
  • mixture of all possible derivatives (16) can be tested at once
    (instead of 16 seperate assays for each derivative created)
  • saves time
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16
Q

After testing a mixture of AB compounds, what do you do if its active versus inactive?

A

Active mixture –> identify the active component
inactive mixture –> store for next HTS

17
Q

Describe what solid-phase organic synthesis (SPOS) is.

A

Starting compound is covalently bound to an insoluble resin bead –> then sequential reactions are performed to produce a library of diverse compounds
* After wash, the compound you want is still bound to the insoluble resin and won’t wash away but everything else will.

18
Q

Explain the Mix and Split synthesis method of library mixtures.

A

Classic method to generate large libraries of compounds.
* Take resin and in 4 seperate vials attach 4 different starting compounds
* Bring the 4 vials together and mix into 1 vial
* Seperate into 4 seperate vials (each now containing A, B, C, and D starting compounds)
* Each vial gets a different reagent added in
* 4 vials get mixed together as 1 again (16 different compounds)
* process can be repeated