Cambridge MedChem Consulting

Bioisosteric Replacements

GABA Bioisosteres

γ-Aminobutyric acid (GABA) is the chief inhibitory neurotransmitter in the mammalian central nervous system and medicinal chemistry programmes have provided an extensive variety of bioisosteric replacements for the carboxylic acid, of particular note is the work of Krogsgaard-Larsen. Much of the work is based on Muscimol an alkaloid isolated from mushrooms and shown to be a potent GABA agonist. A range of heterocycles have now been explored as shown below with the experimental pKa.

More recent work has extend to non-annulated analogues shown below.

Last Update 22 February 2012