3-Hydroxytacrine
Tacrine (THA), the first FDA-approved acetylcholinesterase inhibitor for Alzheimer's disease (AD), was discontinued in 2013 due to its severe hepatotoxicity. This toxicity is largely attributed to the metabolic conversion of THA to 3-Hydroxytacrine7-hydroxytacrine (7-OH-THA), which undergoes further transformation into a reactive quinone methide species, leading to glutathione depletion and liver damage. IC50 AChE 0.623000 microM
General
Type : Derivative of Tacrine, Acridine
Chemical_Nomenclature : 9-amino-1,2,3,4-tetrahydroacridin-3-ol
Canonical SMILES : C1CC2=C(C3=CC=CC=C3N=C2CC1O)N
InChI : InChI=1S\/C13H14N2O\/c14-13-9-3-1-2-4-11(9)15-12-7-8(16)5-6-10(12)13\/h1-4,8,16H,5-7H2,(H2,14,15)
InChIKey : WGAVIJGEWZDOOU-UHFFFAOYSA-N
Other name(s) : R32E49V3H2 || RefChem:911429 || 7-Hydroxytacrine || 7-OH-THA || 3-OH-THA || CHEMBL1127 || SCHEMBL9547668
MW : 214.26
Formula : C13H14N2O
CAS_number : 178450-86-7
PubChem : 10104685
UniChem : WGAVIJGEWZDOOU-UHFFFAOYSA-N
Target
References (3)
| Title : 7-substituted tacrine derivatives: Overcoming tacrine's hepatotoxicity while enhancing therapeutic potential in Alzheimer's disease - Korabecny_2025_J.Neurol.Sci_480_ |
| Author(s) : Korabecny J , Svobodova B , Novak M , Horak M , Soukup O |
| Ref : Journal of the Neurological Sciences , 480 : , 2025 |
| Abstract : |
| PubMedSearch : Korabecny_2025_J.Neurol.Sci_480_ |
| PubMedID: |
| Title : Metabolic disposition of the cognition activator tacrine in rats, dogs, and humans. Species comparisons - Pool_1997_Drug.Metab.Dispos_25_590 |
| Author(s) : Pool WF , Reily MD , Bjorge SM , Woolf TF |
| Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 25 :590 , 1997 |
| Abstract : |
| PubMedSearch : Pool_1997_Drug.Metab.Dispos_25_590 |
| PubMedID: 9152598 |
| Title : The effect of enzyme inhibition on the metabolism and activation of tacrine by human liver microsomes - Spaldin_1994_Br.J.Clin.Pharmacol_38_15 |
| Author(s) : Spaldin V , Madden S , Pool WF , Woolf TF , Park BK |
| Ref : British Journal of Clinical Pharmacology , 38 :15 , 1994 |
| Abstract : |
| PubMedSearch : Spaldin_1994_Br.J.Clin.Pharmacol_38_15 |
| PubMedID: 7946932 |