Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and efficacious gamma-secretase inhibitors (Part II).
Significant improvement in metabolic stability on the pyrazolopiperidine scaffold over the original series were achieved and this stability improvement translated in an improved in vivo efficacy.
Ye
Xiaocong M
XM
Department of Medicinal Chemistry, Elan Pharmaceuticals, South San Francisco, CA 94080, USA. michael.ye@elan.com
Konradi
Andrei W
AW
Smith
Jenifer
J
Aubele
Danielle L
DL
Garofalo
Albert W
AW
Marugg
Jennifer
J
Neitzel
Marty L
ML
Semko
Chris M
CM
Sham
Hing L
HL
Sun
Minghua
M
Truong
Anh P
AP
Wu
Jing
J
Zhang
Hongbin
H
Goldbach
Erich
E
Sauer
John-Michael
JM
Brigham
Elizabeth F
EF
Bova
Michael
M
Basi
Guriqbal S
GS
D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000818:Animals; D055808:Drug Discovery; D004355:Drug Stability; D008862:Microsomes, Liver / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D010880:Piperidines; D011480:Protease Inhibitors; D013449:Sulfonamides; D053829:Amyloid Precursor Protein Secretases