Structure-Activity Studies of 1<i>H</i>-Imidazo[4,5-<i>c</i>]quinolin-4-amine Derivatives as A₃ Adenosine Receptor Positive Allosteric Modulators.

ABSTRACT: We previously reported 1H-imidazo[4,5-c]quinolin-4-amines as A₃ adenosine receptor (A₃AR) positive allosteric modulators (PAMs). A₃AR agonists, but not PAMs, are in clinical trials for inflammatory diseases and liver conditions. We synthesized new analogues to distinguish 2-cyclopropyl antagonist 17 (orthosteric interaction demonstrated by binding and predicted computationally) from PAMs (derivatives with large 2-alkyl/cycloalkyl/bicycloalkyl groups). We predicted PAM binding at a hydrophobic site on the A₃AR cytosolic interface. Although having low Caco-2 permeability and high plasma protein binding, hydrophobic 2-cyclohept-4-enyl-N-3,4-dichlorophenyl, MRS7788 18, and 2-heptan-4-yl-N-4-iodophenyl, MRS805

SUBMITTER: Fallot LB 

PROVIDER: S-EPMC10354740 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature