Histamine analogues. 33rd communication: 2-phenylhistamines with high histamine H1-agonistic activity

Article abstract of DOI:10.1016/0223-5234(90)90132-M

2-Phenylhistamines with various substituents at the phenyl ring were synthesized and the influence of substitution in ortho, meta or para position on histamine H₁-agonistic activity was investigated.Compounds with high activity occured in the meta phenyl series.Increased activity in the guinea-pig ileum assay was achieved by monosubstitution with halogen on the phenyl ring. 2-<2-(3-Fluorophenyl)-4-imidazolyl>ethanamine (12) is the most potent highly selective H₁-agonist known so far, showing 87percent relative potency compared with histamine and full efficacy at theH₁-receptor.Relative activities of the 3-chloro analogue (11) and the 3-methyl analogue (13) are 81percent and 29percent, respectively.Histamine H₂-activity could not be detected. 2-Phenylhistamines are available via reaction of the corresponding benzimidates with 2-oxo-4-phthalimido-1-butyl acetate (6) in liquid ammonia.