TY - JOUR
T1 - Prolonged stability by cyclization
T2 - Macrocyclic phosphino dipeptide isostere inhibitors of β-secretase (BACE1)
AU - Huber, Timo
AU - Manzenrieder, Florian
AU - Kuttruff, Christian A.
AU - Dorner-Ciossek, Cornelia
AU - Kessler, Horst
PY - 2009/8/1
Y1 - 2009/8/1
N2 - Cyclization of recently reported linear phosphino dipeptide isostere inhibitors of BACE1 via side chain olefin metathesis yielded macrocyclic BACE1 inhibitors. The most potent compound II-P1 (IC50 of 47 nM) and the corresponding linear analog I were tested for serum stability. The approach led to three times prolonged half life serum stability of 44 min for the macrocyclic inhibitor II-P1 compared to the linear compound I.
AB - Cyclization of recently reported linear phosphino dipeptide isostere inhibitors of BACE1 via side chain olefin metathesis yielded macrocyclic BACE1 inhibitors. The most potent compound II-P1 (IC50 of 47 nM) and the corresponding linear analog I were tested for serum stability. The approach led to three times prolonged half life serum stability of 44 min for the macrocyclic inhibitor II-P1 compared to the linear compound I.
KW - Alzheimer's disease
KW - BACE1
KW - Macrocyclic
KW - Phosphino dipeptide isostere
KW - Serum stability
KW - β-Secretase
UR - http://www.scopus.com/inward/record.url?scp=67649981158&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2009.05.053
DO - 10.1016/j.bmcl.2009.05.053
M3 - Article
C2 - 19523824
AN - SCOPUS:67649981158
SN - 0960-894X
VL - 19
SP - 4427
EP - 4431
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 15
ER -