Chemistry:CGP-7930

From HandWiki

CGP-7930 was the first positive allosteric modulator of GABAB receptors described in literature.[1][2][3][4] CGP7930 is also a GABAA receptor positive allosteric modulator and a blocker of Potassium channels.[5]

CGP7930 was developed in Novartis and has been used extensively for scientific research. It has anxiolytic effects in animal studies,[6][7] and has a synergistic effect with GABAB agonists such as baclofen and GHB,[8][9] as well as reducing self-administration of alcoholic drinks and cocaine.[10][11]

CNS Review:[12]

Synthesis

The chemical synthesis has been described:[13] Starting material:[14] Product of first step:[15][16]

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%.[17]

See also

  • ASP-8062
  • ADX-71441

References

  1. ↑ "Positive allosteric modulation of native and recombinant gamma-aminobutyric acid(B) receptors by 2,6-Di-tert-butyl-4-(3-hydroxy-2,2-dimethyl-propyl)-phenol (CGP7930) and its aldehyde analog CGP13501". Molecular Pharmacology 60 (5): 963–71. November 2001. PMID 11641424. 
  2. ↑ "The heptahelical domain of GABA(B2) is activated directly by CGP7930, a positive allosteric modulator of the GABA(B) receptor". The Journal of Biological Chemistry 279 (28): 29085–91. July 2004. doi:10.1074/jbc.M400930200. PMID 15126507. 
  3. ↑ "Differential modulation by the GABAB receptor allosteric potentiator 2,6-di-tert-butyl-4-(3-hydroxy-2,2-dimethylpropyl)-phenol (CGP7930) of synaptic transmission in the rat hippocampal CA1 area". The Journal of Pharmacology and Experimental Therapeutics 317 (3): 1170–7. June 2006. doi:10.1124/jpet.105.099176. PMID 16507713. 
  4. ↑ "CGP7930: a positive allosteric modulator of the GABAB receptor". CNS Drug Reviews 13 (3): 308–16. doi:10.1111/j.1527-3458.2007.00021.x. PMID 17894647. 
  5. ↑ "CGP7930 - An allosteric modulator of GABABRs, GABAARs and inwardly-rectifying potassium channels". Neuropharmacology 109644. July 2023. doi:10.1016/j.neuropharm.2023.109644. PMID 37422181. https://discovery.ucl.ac.uk/10173266/1/1-s2.0-S0028390823002344-main.pdf. 
  6. ↑ "Effects of GABAB receptor ligands in animal tests of depression and anxiety". Pharmacological Reports 59 (6): 645–55. PMID 18195453. 
  7. ↑ "Evaluation of the anxiolytic-like profile of the GABAB receptor positive modulator CGP7930 in rodents". Neuropharmacology 54 (5): 854–62. April 2008. doi:10.1016/j.neuropharm.2008.01.004. PMID 18328507. 
  8. ↑ "In vivo effectiveness of CGP7930, a positive allosteric modulator of the GABAB receptor". European Journal of Pharmacology 504 (3): 213–6. November 2004. doi:10.1016/j.ejphar.2004.10.008. PMID 15541424. 
  9. ↑ "The CGP7930 analogue 2,6-di-tert-butyl-4-(3-hydroxy-2-spiropentylpropyl)-phenol (BSPP) potentiates baclofen action at GABA(B) autoreceptors". Clinical and Experimental Pharmacology & Physiology 35 (9): 1113–5. September 2008. doi:10.1111/j.1440-1681.2008.04948.x. PMID 18430050. 
  10. ↑ "The GABA(B) receptor allosteric modulator CGP7930, like baclofen, reduces operant self-administration of ethanol in alcohol-preferring rats". Neuropharmacology 50 (5): 632–9. April 2006. doi:10.1016/j.neuropharm.2005.11.011. PMID 16406445. 
  11. ↑ "Effects of GABA(B) receptor antagonist, agonists and allosteric positive modulator on the cocaine-induced self-administration and drug discrimination". European Journal of Pharmacology 574 (2-3): 148–57. November 2007. doi:10.1016/j.ejphar.2007.07.048. PMID 17698060. 
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ Richard Henry Kline, EP0027426 (1983 to The Goodyear Tire & Rubber Company).
  15. ↑ "Reactions of Hindered Phenols. I. Reactions of 4,4’-Dihydroxy-3,5,3’,5’-tetra-tert-butyl Diphenylmethane *". The Journal of Organic Chemistry 22 (11): 1435–1438. November 1957. doi:10.1021/jo01362a033. 
  16. ↑ "Single crystal X-ray structure of 2,6-di-tert-butyl-4-(3-(4-chlorophenyl)-4-methyl-4,5-dihydroisoxazol-5-yl)phenol 1,4-dioxane hemisolvate". Journal of Structural Chemistry 54 (1): 217–222. February 2013. doi:10.1134/S0022476613010368. 
  17. ↑ 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.

{{Navbox | name = GABA receptor modulators | title = GABA receptor modulators | state = collapsed | bodyclass = hlist | groupstyle = text-align:center; 

 | group1 = Ionotropic
 |  list1 = {{Navbox|subgroup
 | groupstyle = text-align:center
 | groupwidth = 5em

   | group1 = GABAA
   | list1  = 

   | group2 = GABAA-ρ
   | list2  = 

 }}

 | group2 = Metabotropic

| list2 =

GABAB
 | below =
See also
Receptor/signaling modulators
GABAA receptor positive modulators
GABA metabolism/transport modulators

}}



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:CGP-7930&oldid=4028218"