Chiral switches template

Three marketed “chiral switches”: omeprazole → esomeprazole, citalopram → escitalopram and cetirizine → levocetirizine — a racemate re-developed as the single active enantiomer, with the stereochemistry drawn.

What the template shows

• A racemic drug re-developed as its single active enantiomer (eutomer)
• Racemate → single enantiomer
• Omeprazole → esomeprazole
• omeprazole (racemate)
• The (S)-enantiomer of the proton-pump inhibitor; the stereocentre is the sulfoxide sulfur.
• Citalopram → escitalopram
• citalopram (racemate)
• The (S)-enantiomer of the SSRI carries the activity; the (R)-form is essentially inactive.
• Cetirizine → levocetirizine
• cetirizine (racemate)
• The (R)-enantiomer of the antihistamine binds the H₁ receptor more tightly.
• A chiral switch re-develops a drug sold as a racemate as its single active enantiomer (the eutomer).
• Benefits can include a lower dose, a cleaner profile if the other enantiomer (distomer) is inactive or adds side effects, and fresh patent life.
• The two enantiomers are the same constitution but mirror images; only the stereocentre configuration differs.
• Not every switch is worth it — sometimes the racemate is just as good, or the enantiomers interconvert in vivo.
• Agranat, Caner & Caldwell, Nat. Rev. Drug Discov. 2002, 1, 753 · every part of this sheet is editable

Drawn with 150 atoms, 4 shapes – every one editable in MolDraw.

Sources

• Agranat, Caner & Caldwell, Nat. Rev. Drug Discov. 2002, 1, 753 Review