TITLE:
“Atropisomeric” Drugs: Basic Concept and Example of Application to Drug Development
AUTHORS:
Robert B. Raffa, Joseph V. Pergolizzi Jr., Robert Taylor Jr.
KEYWORDS:
Atropisomer, Chirality, Pharmacotherapy, Drug Development, NaV1.7 Inhibitor
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.11 No.1,
January
7,
2020
ABSTRACT:
Many therapeutic drugs are racemates; i.e. they are chiral molecules consisting of “left”- and “right-handed”
enantiomers (stereoisomers that are mirror images
of each other, and are non-superimposable). In some cases, both enantiomers
of the drug contribute to some extent (or equally) to the therapeutic effect; in other cases they contribute not at all. The same is true for the
adverse effects of racemate drugs: the adverse effects of a racemate drug can
be greater-than, less-than, or equal to one or the other enantiomer. An unusual
situation arises when a drug consists of “atropisomers”, stereoisomers arising
because of hindered rotation about a single chemical bond. We summarize the
concept of atropisomerism, and give examples.