ChemInform Abstract: Research on Heterocyclic Compounds. Part 33. Synthesis and Analgesic Activity of Imidazo(1,2‐b)pyridazine‐2‐acetic Acid Derivatives.

Abstract

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Discovery of 2-(Imidazo[1,2-b]pyridazin-2-yl)acetic Acid as a New Class of Ligands Selective for the γ-Hydroxybutyric Acid (GHB) High-Affinity Binding Sites

“…The new gabazine analogues 3a – g , 3k – m , 4a – c , 4h , 4i , 5b – 5e , 5h – j , and 6 were synthesized as depicted in Schemes – . Compounds 3a , 6 , and 15 were synthesized according to procedures reported in the literature, whereas compounds 8a – i were synthesized according to a modified procedure previously described in the literature (please refer to Experimental Section for further information). Compound 7 was obtained from a commercial vendor.…”

“…The imidazopyridazine analogues ( 5b – e and 5h – j , Scheme ) were synthesized by inspiration from a procedure previously published by Luraschi et al, starting from 8b – e and 8h – j and ethyl 4-ethylchloroacetoacetate in ethanol . The ethyl-protected imidazopyridazine analogues ( 13b – e and 13h – j ) were deprotected to afford gabazine analogues 5b – e and 5h – j .…”

“…The imidazopyridazine analogues (5b−e and 5h−j, Scheme 3) were synthesized by inspiration from a procedure previously published by Luraschi et al, starting from 8b−e and 8h−j and ethyl 4-ethylchloroacetoacetate in ethanol. 31 The ethylprotected imidazopyridazine analogues (13b−e and 13h−j) were deprotected to afford gabazine analogues 5b−e and 5h−j. To further investigate the importance of the distal aryl group in this series of gabazine analogues at the GABA A R and the GHB binding sites, the unsubstituted imidazopyridazine analogue 6 was synthesized from compound 14, as described by Luraschi et al (Scheme 3).…”

“…To further investigate the importance of the distal aryl group in this series of gabazine analogues at the GABA A R and the GHB binding sites, the unsubstituted imidazopyridazine analogue 6 was synthesized from compound 14, as described by Luraschi et al (Scheme 3). 31 The pharmacological evaluation of 4a−c, 4h, 4i, 5b−e, 5h− j, 6, and 7 at the GABA A Rs and GHB high-affinity binding sites revealed a number of interesting observations (Table 2). Linking the exo-amino group to the butyric acid side chain afforded two series of analogues containing dihydroimidazopyridazine (4a−c, 4h, and 4i) or imidazopyridazine (5b−e and 5h−j) scaffolds with complete loss of GABA A R affinity.…”

Imidazopyridazine Acetylcholinesterase Inhibitors Display Potent Anti-Proliferative Effects in the Human Neuroblastoma Cell-Line, IMR-32

“…Imidazo[1,2- b ]pyridazine compounds have emerged as an important pharmacophore with a broad spectrum of biological activity including analgesic and anti-inflammatory properties [ 13 , 14 ]. In our previous study, we introduced a nitro group at the 3′ position and an amino group at the 6′ position of the imidazo[1,2- b ]pyridazine skeleton, generating 12 substituents (5a–5l), which exhibited varying AChE inhibitory activity [ 15 ].…”