Drugs Against Neurodegenerative Diseases: Design and Synthesis of 6‐Amino–substituted Imidazo[1,2‐ <i>b</i> ]pyridazines as Acetylcholinesterase Inhibitors

Abstract

Abstract 3‐nitro‐6‐amino substituted –imidazo [1,2‐b]pyridazine derivatives (5a–5 l) were synthesized in four steps and characterized by FT‐IR, 1 H NMR, 13 C NMR and HRMS. 3‐nitro‐6‐amino substituted –imidazo [1,2‐b]pyridazine derivatives (5a‐l) was evaluated for the acetylcholinesterase (AChE) inhibition and antioxidant activities. In both the studies, 3‐nitro‐6‐amino substituted –imidazo [1,2‐b]pyridazine derivatives (5j‐l) were inactive. 3‐nitro‐6‐(piperidin‐1‐yl)imidazo[1,2‐b]pyridazine (5c), substituted with piperidine and 3‐nitro‐6‐(4‐phenylpiperazin‐1‐yl) imidazo[1,2‐b] pyridazine (5 h), substituted with 1‐phenylpiperazine were the most potent compounds (IC 50 &lt;0.05 μM for AChE inhibition activity). Latterly, the most potent compounds 3‐nitro‐6‐(4‐phenylpiperazin‐1‐yl) imidazo[1,2‐b] pyridazine (5 h), 3‐nitro‐6‐(piperidin‐1‐yl)imidazo[1,2‐b]pyridazine (5c), and moderately active compounds 3 ‐nitro‐6‐(pyrrolidin‐1‐yl)imidazo[1,2‐b]pyridazine (5b), 6‐morpholino‐3‐nitroimidazo[1,2‐b]pyridazine (5d), 1‐(3‐nitroimidazo[1,2‐b]pyridazin‐6‐yl)piperidine‐4‐carbonitrile (5e), 6‐(4‐ethylpiperazin‐1‐yl)‐3‐nitroimidazo [1,2‐b]pyridazine (5 g), Tert‐butyl 4‐(3‐nitroimidazo[1,2‐b] pyridazin‐6‐yl) piperazine‐1‐carboxylate (5i) were selected for in vivo study.