Aims: Our research aimed to evaluate how the rigidification of the characteristic 3-aminopropyloxy linker by incorporating it into 1,5-benzoxazepines affects the potency of histamine H3 receptor (H3R) antagonists/inverse agonists. This research constitutes a starting point for the full characterization of the pharmacological properties of this group of compounds. Materials & methods: Several 1,5-benzoxazepine derivatives were synthesized and pharmacologically tested as potential H3R antagonist/inverse agonists. In a addition, the effect of the derivatives on acetylcholinesterase and butyrylcholinesterase inhibition and cytotoxicity were tested. Results: The studies indicated 1,5-benzoxazepine containing three carbon side chains as a compound for further modification. Conclusion: Further optimization of the lead structure is necessary, which will favorably affect biological targets.
Keywords: 1,5-benzoxazepine; Alzheimer's disease; H3 receptor antagonist; anticancer; cholinesterase; histamine.