Substituted Purines as High-Affinity Histamine H₃ Receptor Ligands.

ABSTRACT: Continuing with our program to obtain new histamine H3 receptor (H3R) ligands, in this work we present the synthesis, H3R affinity and in silico studies of a series of eight new synthetically accessible purine derivatives. These compounds are designed from the isosteric replacement of the scaffold presented in our previous ligand, pyrrolo[2,3-d]pyrimidine ring, by a purine core. This design also considers maintaining the fragment of bipiperidine at C-4 and aromatic rings with electron-withdrawing groups at N-9, as these fragments are part of the proposed pharmacophore. The in vitro screening results show that two purine derivatives, 3d and 3h, elicit high affinities to the H3R (Ki values of 2.91 and 5.51 nM, respectively). Both compounds are more potent than the reference drug pitolisant (

SUBMITTER: Espinosa-Bustos C 

PROVIDER: S-EPMC9145483 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature