| 词条 | AL-34662 |
| 释义 |
| Verifiedfields = changed | verifiedrevid = 477235652 | IUPAC_name = 1-((S)-2-Aminopropyl)-1H-indazol-6-ol | image = AL-34662_structure.png | width = 180 | tradename = | pregnancy_AU = | pregnancy_US = | pregnancy_category = | legal_AU = | legal_CA = | legal_UK = | legal_US = | legal_status = | routes_of_administration = | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion = | CAS_number_Ref = {{cascite|changed|??}} | CAS_number = 210580-75-9 | ATC_prefix = | ATC_suffix = | PubChem = | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 21467821 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 371300 | C=10 | H=13 | N=3 | O=1 | molecular_weight = 191.229 g/mol | smiles = CC(N)Cn1ncc2ccc(O)cc12 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C10H13N3O/c1-7(11)6-13-10-4-9(14)3-2-8(10)5-12-13/h2-5,7,14H,6,11H2,1H3/t7-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = WBYHTZYHAFNBKW-ZETCQYMHSA-N | melting_point = 170 | melting_high = 172 }}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
References1. ^{{cite journal | last1 = Sharif | first1 = NA | last2 = Kelly | first2 = CR | last3 = Crider | first3 = JY | last4 = Davis | first4 = TL | title = Serotonin-2 (5-HT2) receptor-mediated signal transduction in human ciliary muscle cells: role in ocular hypotension | journal = Journal of Ocular Pharmacology and Therapeutics | volume = 22 | issue = 6 | pages = 389–401 | year = 2006 | pmid = 17238805 | doi = 10.1089/jop.2006.22.389 }} {{Serotonergics}}2. ^{{cite journal | last1 = Sharif | first1 = NA | last2 = McLaughlin | first2 = MA | last3 = Kelly | first3 = CR | title = AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist | journal = Journal of Ocular Pharmacology and Therapeutics | volume = 23 | issue = 1 | pages = 1–13 | year = 2007 | pmid = 17341144 | doi = 10.1089/jop.2006.0093 }} 3. ^{{cite journal | last1 = May | first1 = JA | last2 = Chen | first2 = HH | last3 = Rusinko | first3 = A | last4 = Lynch | first4 = VM | last5 = Sharif | first5 = NA | last6 = McLaughlin | first6 = MA | title = A novel and selective 5-HT2 receptor agonist with ocular hypotensive activity: (S)-(+)-1-(2-aminopropyl)-8,9-dihydropyrano3,2-eindole | journal = Journal of Medicinal Chemistry | volume = 46 | issue = 19 | pages = 4188–95 | year = 2003 | pmid = 12954071 | doi = 10.1021/jm030205t }} 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. ^{{cite journal | last1 = May | first1 = JA | last2 = Dantanarayana | first2 = AP | last3 = Zinke | first3 = PW | last4 = McLaughlin | first4 = MA | last5 = Sharif | first5 = NA | title = 1-((S)-2-aminopropyl)-1H-indazol-6-ol: a potent peripherally acting 5-HT2 receptor agonist with ocular hypotensive activity | journal = Journal of Medicinal Chemistry | volume = 49 | issue = 1 | pages = 318–28 | year = 2006 | pmid = 16392816 | doi = 10.1021/jm050663x }} 4 : Indazoles|Amines|Peripherally selective drugs|Serotonin receptor agonists |
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