2-Substituted (N)-Methanocarba A₃ Adenosine Receptor Agonists: In Silico, In Vitro, and In Vivo Characterization.

ABSTRACT: 2-Arylethynyl (N)-methanocarba adenosine 5'-methylamides are selective A₃ adenosine receptor (AR) agonists containing a preestablished receptor-preferred pseudoribose conformation. Here, we compare analogues having bulky 2-substitution, either containing or lacking an ethynyl spacer between adenine and a cyclic group. 2-Aryl compounds 9-11, 13, 14, 19, 22, 23, 27, 29, 31, and 34, lacking a spacer, had human (h) A₃AR K _i values of 2-30 nM, and others displayed lower affinity. Mouse (m) A₃AR affinity varied, with 2-arylethynyl having a higher affinity than 2-aryl analogues (7, 8 > 3c, 3d > 3b). However, 2-aryl-4'-truncated derivati

SUBMITTER: Tosh DK 

PROVIDER: S-EPMC11249627 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature