INTRODUCTION TO DRUG DISCOVERY
FINAL EXAM QUESTIONS WITH
COMPLETE SOLUTIONS
Pooled synthesis - ANSWER-a method that doesn't make you create each compound
individually
split pool strategy - ANSWER-splitting up products and redistribution them is called a
split pool strategy
combinatorial chemistry - ANSWER-the synthesis of larger organic molecules from
smaller ones
encoding library - ANSWER-put a small piece of DNA (tagging) on the beads
PCR - ANSWER-amplifying the DNA that is present to determine the compound
Drawbacks to solid-phase synthesis - ANSWER--compounds are typically cleaved with
TFA
-cleavage leads to some decomposition of products
-inefficient removal of TFA leads to limited their life of compounds prepared in this
manner
fluorous technology - ANSWER-causes it to not be happy in water or in organic phase
parallel organic synthesis - ANSWER-a robot is used to automate the synthesis
What are the advantages of having a large number of analogs? - ANSWER--removes
synthesis as a bottleneck to progress
-provides a level of confidence that any activity's seen is not a fluke
-provides rapid access to SAR
What reactions lend themselves to late-stage diversity? - ANSWER-Suzuki reaction and
buchwald-hartwig reaction
Suzuki reaction - ANSWER-connects any two aromatic together with the presence of a
boron and halide reacting with palladium.
Advantages of a Suzuki reaction - ANSWER--formation of C-C bond doesn't add to the
number of H-bond donors/acceptors
-does not add to the PSA
-thousands of boronic acids are commercially available
, Buchwald-Hartwig reaction - ANSWER-a halide reacting with a amine or alcohol under
palladium and base conditions.
Advantages to Buchwald-Hartwig reactions - ANSWER--heterocycles can be introduced
-are amenable to solid-phase synthesis
How do you speed up reactions? - ANSWER-automation, vessel stirrers, parallel
purifiers, robotics, well plates, LC/MS, and NMR
What should you do when there is more than one binding interaction? - ANSWER--try
and determine the optimal distance between the interaction by ring
expansion/contraction
-when flexible, try to impose rigidity
-avoid stereochemistry
isosteres - ANSWER-one of two ore more substances that exhibit similarity of some
properties as a result of having the same number of valence electrons in the same
arrangement that have different atoms and amounts
bioisoster - ANSWER-substituents with similar properties that broadly produce similar
biological properties
Examples of bioisosteres - ANSWER--replace a hydrogen with fluorine
-thymidine and AZT
Prodrugs - ANSWER-when the active substance isn't the drug, but gets converted in the
body to the drug wanted
pharmacodynamics - ANSWER-what the drug does to the body
Xenografts - ANSWER-a human tumor is taken and placed with a different host with the
hopes of transplanting it back into the human
What type of mouse is required for xenografts? - ANSWER-an immunodeficient mouse
(aka a nude mouse)
Types of biomarkers - ANSWER-response, predictive, safety, risk, diagnostic, and
monitoring
biomarker - ANSWER-biochemical response measured from a living organism
Efficacy - ANSWER-the real litmus test for a potential drug
Ways to measure efficacy - ANSWER--rat paw edema test
-rat tail flick test
-forced swim test
FINAL EXAM QUESTIONS WITH
COMPLETE SOLUTIONS
Pooled synthesis - ANSWER-a method that doesn't make you create each compound
individually
split pool strategy - ANSWER-splitting up products and redistribution them is called a
split pool strategy
combinatorial chemistry - ANSWER-the synthesis of larger organic molecules from
smaller ones
encoding library - ANSWER-put a small piece of DNA (tagging) on the beads
PCR - ANSWER-amplifying the DNA that is present to determine the compound
Drawbacks to solid-phase synthesis - ANSWER--compounds are typically cleaved with
TFA
-cleavage leads to some decomposition of products
-inefficient removal of TFA leads to limited their life of compounds prepared in this
manner
fluorous technology - ANSWER-causes it to not be happy in water or in organic phase
parallel organic synthesis - ANSWER-a robot is used to automate the synthesis
What are the advantages of having a large number of analogs? - ANSWER--removes
synthesis as a bottleneck to progress
-provides a level of confidence that any activity's seen is not a fluke
-provides rapid access to SAR
What reactions lend themselves to late-stage diversity? - ANSWER-Suzuki reaction and
buchwald-hartwig reaction
Suzuki reaction - ANSWER-connects any two aromatic together with the presence of a
boron and halide reacting with palladium.
Advantages of a Suzuki reaction - ANSWER--formation of C-C bond doesn't add to the
number of H-bond donors/acceptors
-does not add to the PSA
-thousands of boronic acids are commercially available
, Buchwald-Hartwig reaction - ANSWER-a halide reacting with a amine or alcohol under
palladium and base conditions.
Advantages to Buchwald-Hartwig reactions - ANSWER--heterocycles can be introduced
-are amenable to solid-phase synthesis
How do you speed up reactions? - ANSWER-automation, vessel stirrers, parallel
purifiers, robotics, well plates, LC/MS, and NMR
What should you do when there is more than one binding interaction? - ANSWER--try
and determine the optimal distance between the interaction by ring
expansion/contraction
-when flexible, try to impose rigidity
-avoid stereochemistry
isosteres - ANSWER-one of two ore more substances that exhibit similarity of some
properties as a result of having the same number of valence electrons in the same
arrangement that have different atoms and amounts
bioisoster - ANSWER-substituents with similar properties that broadly produce similar
biological properties
Examples of bioisosteres - ANSWER--replace a hydrogen with fluorine
-thymidine and AZT
Prodrugs - ANSWER-when the active substance isn't the drug, but gets converted in the
body to the drug wanted
pharmacodynamics - ANSWER-what the drug does to the body
Xenografts - ANSWER-a human tumor is taken and placed with a different host with the
hopes of transplanting it back into the human
What type of mouse is required for xenografts? - ANSWER-an immunodeficient mouse
(aka a nude mouse)
Types of biomarkers - ANSWER-response, predictive, safety, risk, diagnostic, and
monitoring
biomarker - ANSWER-biochemical response measured from a living organism
Efficacy - ANSWER-the real litmus test for a potential drug
Ways to measure efficacy - ANSWER--rat paw edema test
-rat tail flick test
-forced swim test
