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AL-34662
Systematic (IUPAC) name
1-((S)-2-Aminopropyl)-1H-indazol-6-ol
Identifiers
CAS number  ?
ATC code  ?
PubChem  ?
Chemical data
Formula C 10H13N3O 
Mol. mass 191.229 g/mol
SMILES eMolecules & PubChem
Physical data
Melt. point 170–172 °C (338–342 °F)
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.  ?
Legal status
Routes  ?

AL-34662 is an indazole derivative drug which is being developed for the treatment of glaucoma. It acts as a selective 5-HT2A receptor agonist, the same target as that of hallucinogenic 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 which 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

References

  1. ^ Sharif NA, Kelly CR, Crider JY, Davis TL. Serotonin-2 (5-HT2) receptor-mediated signal transduction in human ciliary muscle cells: role in ocular hypotension. Journal of Ocular Pharmacology and Therapeutics. 2006 Dec;22(6):389-401. PMID 17238805
  2. ^ Sharif NA, McLaughlin MA, Kelly CR. AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist. Journal of Ocular Pharmacology and Therapeutics. 2007 Feb;23(1):1-13. PMID 17341144
  3. ^ May JA, Chen HH, Rusinko A, Lynch VM, Sharif NA, McLaughlin MA. A novel and selective 5-HT2 receptor agonist with ocular hypotensive activity: (S)-(+)-1-(2-aminopropyl)-8,9-dihydropyrano[3,2-e]indole. Journal of Medicinal Chemistry. 2003 Sep 11;46(19):4188-95. 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. 1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity. Journal of Medicinal Chemistry. 2006 Jan 12;49(1):318-28. PMID 16392816
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