Title : Synthesis of novel phenserine-based-selective inhibitors of butyrylcholinesterase for Alzheimer's disease - Yu_1999_J.Med.Chem_42_1855 |
Author(s) : Yu Q , Holloway HW , Utsuki T , Brossi A , Greig NH |
Ref : Journal of Medicinal Chemistry , 42 :1855 , 1999 |
Abstract :
Four novel analogues (8-11) of cymserine (2) were synthesized by methods similar to those recently developed for the total syntheses of N8-norphenserine (Yu, Q. S.; et al. J. Med. Chem. 1997, 40, 2895-2901) and N1,N8-bisnorphenserine (Yu, Q. S.; et al. J. Med. Chem. 1998, 41, 2371-2379). As our structure-activity studies predicted, these compounds are highly potent and selective inhibitors of human butyrylcholinesterase (BChE) and will test the novel hypothesis that BChE inhibitors are useful in the treatment of Alzheimer's disease. In a similar manner, the same modifications that provided BChE selectivity were applied to the acetylcholinesterase (AChE)-selective inhibitor, tolserine (5), to provide the novel tolserine analogues 12-15. As predicted, these modifications altered the AChE-selective action of tolserine (5) to favor a lack of cholinesterase enzyme subtype selectivity. |
PubMedSearch : Yu_1999_J.Med.Chem_42_1855 |
PubMedID: 10346939 |
Yu Q, Holloway HW, Utsuki T, Brossi A, Greig NH (1999)
Synthesis of novel phenserine-based-selective inhibitors of butyrylcholinesterase for Alzheimer's disease
Journal of Medicinal Chemistry
42 :1855
Yu Q, Holloway HW, Utsuki T, Brossi A, Greig NH (1999)
Journal of Medicinal Chemistry
42 :1855