The Synthesis and Evaluation of Fluoro‐, Trifluoromethyl‐, and Iodomuscimols as GABA Agonists

Abstract

Halogenated analogues of the neurotoxic alkaloid muscimol were prepared with fluorine, iodine or trifluoromethyl at the 4 position of the isoxazole ring system. These compounds were investigated as agonists for GABA receptors. Only the C-4 fluorine-containing analogue proved to be an active compound in these assays. The fluoro analogue was less active than muscimol, however it showed differential activity between synaptic (α β γ ) and extrasynaptic (α β γ) GABA receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α β γ) receptor.

[3-Methoxy-5-(methoxycarbonyl)isoxazol-4-yl](4-methoxyphenyl)iodonium 2,2,2-trifluoroacetate

“…The versatility of isoxazoles core components in biologically active compounds, natural products and functional materials (Abdul Manan et al, 2017;Frolund et al, 2002;Lee et al, 2009) led us to examine the synthesis of iodonoum salts bearing an isoxazole motif possessing novel structural features with the possibly of some interest as a precursor to fluoroisoxazole.…”

Trifluoromethyl‐β‐dicarbonyls as Versatile Synthons in Synthesis of Heterocycles

“…Trifluoromethylated heterocycles have been increasingly valuable molecules because of their wide array of pharmacological activities as antiviral, [14] antifungal, [15] antibacterial, [16] insecticidal, [17] antiinflammatory, [18] anticancer, [19,20] antimalarial, [21] antitubercular, [22] herbicide, [23] orally bioavailable inhibitor of factor Xa, [24] as well as adenosine A 3 receptor antagonists [25] and GABA A receptors agonists. [26] They also have broad application prospects in the field of organic synthesis, [27,28] electronics, [29] and electromobility [30] and dyes [31] etc. Several heterocycles containing CF 3 group as a core structural component like celecoxib, mavacoxib, SC-560, razaxaban, leflunomide, sarolaner, sitagliptin, mefloquine, lansoprazole, sorafenib, gemigliptin, efavirenz, tipranavir, enasidenib, doravirine, pexidartinib etc.…”

“…Therefore, hosting CF 3 group is key strategy for enhancing the activity of drugs or drug candidates. Trifluoromethylated heterocycles have been increasingly valuable molecules because of their wide array of pharmacological activities as antiviral, [14] antifungal, [15] antibacterial, [16] insecticidal, [17] anti‐inflammatory, [18] anticancer, [19,20] antimalarial, [21] antitubercular, [22] herbicide, [23] orally bioavailable inhibitor of factor Xa, [24] as well as adenosine A 3 receptor antagonists [25] and GABA A receptors agonists [26] . They also have broad application prospects in the field of organic synthesis, [27,28] electronics, [29] and electromobility [30] and dyes [31] etc.…”