41 - lipitor 2 Flashcards
why were docs afraid of prescribing statins
- 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
what is four-s study of simvastatin
- 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
describe statins complex structures/difficulty of them
lots of stereocenters and difficult to manufacture, need natural source
what part of statin is important and what is variable and describe
hmg part is important and the vairable part is the flat no stereochemistry area at the bottom
what did merck to with his attempt to make an artificial statin
Simple ring system, no stereochemistry, lipophilic and was used as a template
what is pfizers pyrrole based ring system
- pyrrole= aromatic
- Based on Merck publication
- heteroatom allows you to make a lot more molecules bc C-C is hard to synthesize
describe the pfizer molecule designed for synthesis (link optimization, pyrrole 5-subtituent, bottom substitution)
- tested compounds and looked for the smallest IC50 concentration
what is IC50
inhibitory concentration 50% inhibition
what is the pentasubtituted pyrroles (racemic)
changed the stereo to make it up down and down up racemic mixture
what did pfizer end up developing (natural or unnatural)
single enantiomer that has max potency, it was the natural molecule
why did pfizer want to use lowest dose possible and which ones
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
what number statin drug is lipitor for the market
4 like my grade 11 biology grades
what is biocatalytic chain synthesis
diagram
explain generic versions from improved biocatalysis
notes <3
