Documente Academic
Documente Profesional
Documente Cultură
Proposed Contents
1. Introduction
2. The traditional hydroxyethylamine (HEA) derived inhibitors (potency,
permeability and efflux properties, and in vivo efficacy will be
discussed)
3. Novel aminoheterocyclic derived inhibitors
3.1. The aminoheteroaryls
3.2. The aminoquinoxalines
3.3. The cyclic acylguanidines
3.4. The cyclic amindines
3.5. The aminooxazolidines
3.6. The aminothiazolidines
4. Cyclic amine derived inhibitors
4.1. The pyrrolidines
4.2. The piperidines
4.3. The piperizines
6. Summary
H2N
H2N H2N N O H2N X R1 O
N Y NH2 O
R2 N R3
N O N R3 R3
N N N
R1 H O
R2 R1 R1 R2
R1 R2 R2 N
O R4 O R4 O
O
H2N R5 H2N N
R1 R1 N S
R1 N R N R
N S N N R N 2 R2 3
2
N H H
N R4 R4
N N N R5
R1 R3 R1 R3 R4 = H, F
R2 R2 R3 R3 Z
A
Merck 2009108550 Merck WO2005097767 Merck WO2007011810 Merck WO2007011810 Pfizer WO2009136350
H H
N N
O O H H
H2N X O N R1 R3 N R1 R1 N R1 N
H2N X X = S only
X = O, S, NR N R2 R2
N X X
R1 R1 Y n = 0, 1, 2
R2 O
n O
R2 R2 Norvatis
Norvatis EP1707202 WO2009106599
Shionogi EP1942105 (2008) Eisai WO2009091016 Norvatis EP1707206
Specific examples:
Schering-Plough WO2009131975
Schering-Plough WO2009131974
Pfizer
WO2009136350
Data presented on poster
on ACS meeting 2008
BACE1 IC50 = 60 nM
PD data not reported
Wyeth:
Patents
WO2008118379
Patents
WO2009108550
Boehringer-Ingelheim:
WO2009078932
Patents
WO2009007300
Shionogi:
Patents
~80% reduction in rat
brain A, 10 mpk po
WO2007049532 [EP1942105 (2008)]
WO2008133273
WO2008133274
H2N S
O
N
H N
N N
O
F