Drugs Against Neurodegenerative Diseases: Design and Synthesis of 6-Amino-substituted Imidazo[1,2-b]pyridazines as Acetylcholinesterase Inhibitors

3-nitro-6-amino substituted -imidazo [1,2-b] pyridazine derivatives (5a-5 l) were synthesized in four steps and characterized by FT-IR, (HNMR)-H-1, (CNMR)-C-13 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-1yl) imidazo[1,2-b] pyridazine (5 h), substituted with 1-phenylpiperazine were the most potent compounds (IC50 < 0.05 mu M 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-3nitroimidazo[1,2-b] pyridazine (5d), 1-(3-nitroimidazo[1,2-b] pyridazine-6-yl) piperidine-4-carbonitrile (5e), 6-(4-ethylpiperazin-1yl)- 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.