Patent Evaluation: Pyridine H₁ - Receptor Antagonists

Summary

Novelty: Novel benzo[5,6]cyclohepta[1,2b]pyridine derivatives, said to have strong antihistaminergic action, are disclosed. These compounds may be useful for treating bronchial asthma, allergic rhinitis and various pollinoses.

Biology: Antihistaminergic and anti-acetylcholinergic action was evaluated using isolated guinea pig ileum. The IC50 values for the exemplified compound were 1.5 × 10⁻⁸ M and 4.85 × 10⁻⁵ M, respectively. The exemplified compound was found to have extremely high antihistamine selectivity compared to Terfenadine and Loratadine.

Chemistry: The synthesis of the compounds is outlined in six reaction schemes and eighteen examples are given. One hundred and eighty compounds are exemplified including 8-cyano-11-(l-methy1-4-pyridylidene)-6,1 l-dihydro-5H-benzo[5,6]cyclohept[1,2-b]pyridine.

Structure: