Highly Potent, Stable, and Selective Dimeric Hetarylpropylguanidine-Type Histamine H₂ Receptor Agonists.

ABSTRACT: On the basis of the long-known prototypic pharmacophore 3-(1H-imidazol-4-yl)propylguanidine (SK&F 91486, 2), monomeric, homodimeric, and heterodimeric bisalkylguanidine-type histamine H₂ receptor (H₂R) agonists with various alkyl spacers were synthesized. Aiming at increased H₂R selectivity of the ligands, the imidazol-4-yl moiety was replaced by imidazol-1-yl, 2-aminothiazol-5-yl or 2-amino-4-methylthiazol-5-yl according to a bioisosteric approach. All compounds turned out to be partial or full agonists at the h/gp/rH₂R. The most potent analogue, the thiazole-type heterodimeric ligand 63 (UR-Po461), was a partial agonist (E_max = 88%) and 250 times more potent than histamine (pEC_50<

SUBMITTER: Pockes S 

PROVIDER: S-EPMC6130797 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature