41 - lipitor 2

Question 1

why were docs afraid of prescribing statins

Answer 1

• Caused cataracts
• Removed from market
• Case study in textbooks → hehe cataract side effect is famous → just learned that inhibition is bad, not exactly about the enzyme

Question 2

what is four-s study of simvastatin

Answer 2

• Scandinavian Simvastatin Survival Study
• 4,444 patients
• 35 % reduction in cholesterol
• 42 % less likely to die of heart attack
• Non-heart related deaths at normal rates → no nasty side effects
• Sales of all statin drugs rose

Question 3

describe statins complex structures/difficulty of them

Answer 3

lots of stereocenters and difficult to manufacture, need natural source

Question 4

what part of statin is important and what is variable and describe

Answer 4

hmg part is important and the vairable part is the flat no stereochemistry area at the bottom

Question 5

what did merck to with his attempt to make an artificial statin

Answer 5

Simple ring system, no stereochemistry, lipophilic and was used as a template

Question 6

what is pfizers pyrrole based ring system

Answer 6

• pyrrole= aromatic
• Based on Merck publication
• heteroatom allows you to make a lot more molecules bc C-C is hard to synthesize

Question 7

describe the pfizer molecule designed for synthesis (link optimization, pyrrole 5-subtituent, bottom substitution)

Answer 7

• tested compounds and looked for the smallest IC50 concentration

Question 8

what is IC50

Answer 8

inhibitory concentration 50% inhibition

Question 9

what is the pentasubtituted pyrroles (racemic)

Answer 9

changed the stereo to make it up down and down up racemic mixture

Question 10

what did pfizer end up developing (natural or unnatural)

Answer 10

single enantiomer that has max potency, it was the natural molecule

Question 11

why did pfizer want to use lowest dose possible and which ones

Answer 11

so then docs can stop being weewees and prescribe it
Single enantiomer version gave best chance for this
- Racemate 0.025 µM
- Single enantiomer 0.007 µM → oh yeah we pick her

Question 12

what number statin drug is lipitor for the market

Answer 12

4 like my grade 11 biology grades

Question 13

what is biocatalytic chain synthesis

Answer 13

diagram

Question 14

explain generic versions from improved biocatalysis

Answer 14

notes <3