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.
Department of Medicinal Chemistry, Elan Pharmaceuticals, South San Francisco, CA 94080, USA. michael.ye@elan.com
Xiaocong M
XM
Ye
Andrei W
AW
Konradi
Jenifer
J
Smith
Danielle L
DL
Aubele
Albert W
AW
Garofalo
Jennifer
J
Marugg
Marty L
ML
Neitzel
Chris M
CM
Semko
Hing L
HL
Sham
Minghua
M
Sun
Anh P
AP
Truong
Jing
J
Wu
Hongbin
H
Zhang
Erich
E
Goldbach
John-Michael
JM
Sauer
Elizabeth F
EF
Brigham
Michael
M
Bova
Guriqbal S
GS
Basi
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