CAS Number 210580-75-9 N
ChemSpider 21467821 YesY
Chemical and physical data
Formula C10H13N3O
Molar mass 191.229 g/mol
3D model (Jmol) Interactive image
Melting point 170 to 172 °C (338 to 342 °F)
 NYesY (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]

See also


  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 Medicinal 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 Medicinal Chemistry. 49 (1): 318–28. doi:10.1021/jm050663x. PMID 16392816.
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