CGP-7930 was the first positive allosteric modulator of GABAB receptors described in literature. CGP7930 is also a GABAA receptor positive allosteric modulator and a blocker of Potassium channels.
CGP7930 was developed in Novartis and has been used extensively for scientific research. It has anxiolytic effects in animal studies, and has a synergistic effect with GABAB agonists such as baclofen and GHB, as well as reducing self-administration of alcoholic drinks and cocaine.
CNS Review:Ong, J., Kerr, D. I. B. (September 2005). "Clinical Potential of GABA B Receptor Modulators". CNS Drug Reviews. 11 (3): 317–334. doi:10.1111/j.1527-3458.2005.tb00049.x. Synthesis The chemical synthesis has been described:Kerr, David I. B.; Khalafy, Jabbar; Ong, Jennifer; Perkins, Michael V.; Prager, Rolf H.; Puspawati, Ni Made; Rimaz, Mehdi (2006). "Synthesis and Biological Activity of Allosteric Modulators of GABABReceptors, Part 2. 3-(2,6-Bis-tert-butyl-4-hydroxyphenyl)propanols". Australian Journal of Chemistry. 59 (7): 457. doi:10.1071/CH06164. Starting material:Richard Henry Kline, EP0027426 (1983 to The Goodyear Tire & Rubber Company). Product of first step:
2,6-Di-tert-butylphenol is treated with formaldehyde, base and methanol to give [87-97-8] (2). Base catalyzed reaction with isobutaldehyde gives CGP-13501 (3). Hydride reduction of the aldehyde gives the primary alcohol.
According to Krysin (Russia), 2,6-Di-tert-butylphenol is reacted with Neopentyl glycol with lye in an autoclave. Although 1 step reaction, yield was quoted as merely 15%.Krysin, A. P.; Pustovskikh, I. I.; Koptyug, V. A. (2010). "Synthesis of 4-(ω-hydroxyalkyl)-2,6-di-tert-butylphenols and the properties of related sulfides". Russian Journal of General Chemistry. 80 (10): 2001–2006. doi:10.1134/S1070363210100208.
See also ASP-8062 ADX-71441
References