AL-34662

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AL-34662
AL-34662 structure.png
Systematic (IUPAC) name
1-((S)-2-Aminopropyl)-1H-indazol-6-ol
Clinical data
Legal status
?
Identifiers
CAS number 210580-75-9 N
ATC code ?
ChemSpider 21467821 YesY
ChEMBL CHEMBL371300 YesY
Chemical data
Formula C10H13N3O 
Mol. mass 191.229 g/mol
Physical data
Melt. point 170–172 °C (338–342 °F)
 N (what is this?)  (verify)

AL-34662 is an indazole derivative drug that is being developed for the treatment of glaucoma. It acts as a selective 5-HT2A receptor agonist, the same target as that of psychedelic drugs like psilocin, but unlike these drugs, AL-34662 was designed specifically as a peripherally selective drug, which does not cross the blood–brain barrier. This means that AL-34662 can exploit a useful side effect of the hallucinogenic 5-HT2A agonists, namely reduction in intra-ocular pressure and hence relief from the symptoms of glaucoma, but without causing the hallucinogenic effects that make centrally active 5-HT2A agonists unsuitable for clinical use.[1] In animal studies, AL-34662 has been shown to be potent and effective in the treatment of symptoms of glaucoma, with minimal side effects.[2]

Peripherally acting 5-HT2A agonists have been a rich field of research in recent years, with potential glaucoma treatments being the main proposed application for 5-HT2A agonists at present, as centrally acting agonists for this receptor tend to be hallucinogenic and thus have little medical use. While many novel, potent and selective 5-HT2A agonists have been developed for this application,[3][4][5][6][7][8][9][10] retaining peripheral selectivity can be a problem, and several of the more lipophilic compounds closely related to AL-34662 such as those shown below, did cross the blood–brain barrier and produced hallucinogen-appropriate responding in animals.[11]

Hallucinogenic indazoles.png

See also[edit]

References[edit]

  1. ^ Sharif, NA; Kelly, CR; Crider, JY; Davis, TL (2006). "Serotonin-2 (5-HT2) receptor-mediated signal transduction in human ciliary muscle cells: role in ocular hypotension". Journal of Ocular Pharmacology and Therapeutics 22 (6): 389–401. doi:10.1089/jop.2006.22.389. PMID 17238805. 
  2. ^ Sharif, NA; McLaughlin, MA; Kelly, CR (2007). "AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist". Journal of Ocular Pharmacology and Therapeutics 23 (1): 1–13. doi:10.1089/jop.2006.0093. PMID 17341144. 
  3. ^ May, JA; Chen, HH; Rusinko, A; Lynch, VM; Sharif, NA; McLaughlin, MA (2003). "A novel and selective 5-HT2 receptor agonist with ocular hypotensive activity: (S)-(+)-1-(2-aminopropyl)-8,9-dihydropyrano3,2-eindole". Journal of Medical Chemistry 46 (19): 4188–95. doi:10.1021/jm030205t. PMID 12954071. 
  4. ^ Jesse A. May, Paul W. Zinke. 5-Hydroxyl indole derivatives for treating glaucoma. US Patent 6806285
  5. ^ Jesse A. May, Zixia Feng, Anura P. Dantanarayana. 6-hydroxy-indazole derivatives for treating glaucoma. US Patent 6956036
  6. ^ Jesse A. May, Anura P. Dantanarayana. Fused indazoles and indoles and their use for the treatment of glaucoma. US Patent 6960608
  7. ^ Jesse A. May, Zixia Feng. 5-Hydroxy indazole derivatives for treating glaucoma. US Patent 7005443
  8. ^ Zixia Feng, Mark R. Hellberg. Benzodifuranimidazoline and benzofuranimidazoline derivatives and their use for the treatment of glaucoma. US Patent 7208512.
  9. ^ Anura P. Dantanarayana, Jesse Albert May. Substituted (1,4)oxazino(2,3-g)indazoles for the treatment of glaucoma. US Patent 7268131
  10. ^ Anura P. Dantanarayana, Jesse A. May. Substituted 1-alkylamino-1H-indazoles for the treatment of glaucoma. US Patent 7338972
  11. ^ May, JA; Dantanarayana, AP; Zinke, PW; McLaughlin, MA; Sharif, NA (2006). "1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity". Journal of Medical Chemistry 49 (1): 318–28. doi:10.1021/jm050663x. PMID 16392816.