Cambridge MedChem Consulting

Bioisosteric Replacements

Basic Bioisosteres

Bioisosteres offer the opportunity to modulate the pKa of the basic center, to mask very hydrophilic functional groups capable of forming multiple hydrogen bonding interactions. Constrained analogues may no longer be substrates for mono amine oxidase.

Many sample collections contain many, many structures containing the Piperazine motif the bioisosteric described below off the opportunity to modify the pKa of the nitrogens but also subtly alter the directionality of the vectors from the nitrogens.

basic_bioisosteres2

The effect of some of these piperazine bioisosteres have on bioavailability has been described DOI.

basic_bioavail

Hahn et al DOI in their exploration of 3-substituted azetidine based triple reuptake inhibitors described the bioisosteric replacement of 3-akpha-oxyazetidine with 3-aminoazetidine. One advantage of this replacement is the elimination of a chiral centre.

basic_bioisosteres3

Last Update 26 July 2017