| Title : Evaluation of short-tether bis-THA AChE inhibitors. A further test of the dual binding site hypothesis - Carlier_1999_Bioorg.Med.Chem_7_351 |
| Author(s) : Carlier PR , Han YF , Chow ES , Li CP , Wang H , Lieu TX , Wong HS , Pang YP |
| Ref : Bioorganic & Medicinal Chemistry , 7 :351 , 1999 |
|
Abstract :
To provide a further test of the dual binding site hypothesis proposed for acetylcholinesterase (AChE) inhibitor heptylene-linked bis-(9-amino-1,2,3,4-tetrahydroacridine) A7A, short-tether (ethylene hexylene) homologs A2A-A6A were prepared. En route to these compounds, convenient and scaleable syntheses of useful pharmaceutical intermediate 9-chloro-1.2,3,4-tetrahydroacridine 3 and A7A were developed. AChE and butyrylcholinesterase (BChE) inhibition assays of A2A-A10A confirm that a seven methylene tether (A7A) optimizes AChE inhibition potency and AChE/BChE selectivity. Finally, these studies indicate that simultaneous binding of alkylene-linked 9-amino-1,2,3,4-tetrahydroacridine dimers to the catalytic and peripheral sites of AChE is possible with a tether length as short as 5 methylenes |
| PubMedSearch : Carlier_1999_Bioorg.Med.Chem_7_351 |
| PubMedID: 10218828 |
Carlier PR, Han YF, Chow ES, Li CP, Wang H, Lieu TX, Wong HS, Pang YP (1999)
Evaluation of short-tether bis-THA AChE inhibitors. A further test of the dual binding site hypothesis
Bioorganic & Medicinal Chemistry
7 :351
Carlier PR, Han YF, Chow ES, Li CP, Wang H, Lieu TX, Wong HS, Pang YP (1999)
Bioorganic & Medicinal Chemistry
7 :351