Synthesis of 7-benzyl-5-(piperidin-1-yl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c][2,7]naphthyridin-1-ylamine and its analogs as bombesin receptor subtype-3 agonists.
The original structure of a high-throughput screening hit obtained from an external vendor was revised based on multiple NMR studies. The active compound was re-synthesized via a novel route and its structure and biological activity as a BRS-3 agonist were unambiguously confirmed. Multi-gram quantities of the hit were prepared for pharmacokinetic and efficacy studies. The synthetic strategy allowed for the preparation of multiple analogs for SAR exploration.
Guo
Cheng
C
AMRI, 26 Corporate Circle, Albany, NY 12212, USA. cheng.guo@amriglobal.com
Guzzo
Peter R
PR
Hadden
Mark
M
Sargent
Bruce J
BJ
Yet
Larry
L
Kan
Yanqing
Y
Palyha
Oksana
O
Kelly
Theresa M
TM
Guan
Xiaoming
X
Rosko
Kim
K
Gagen
Karen
K
Metzger
Joseph M
JM
Dragovic
Jasminka
J
Lyons
Kathryn
K
Lin
Linus S
LS
Nargund
Ravi P
RP
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D057166:High-Throughput Screening Assays; D006801:Humans; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D018004:Receptors, Bombesin / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
C550999:7-benzyl-5-(piperidin-1-yl)-6,7,8,9-tetrahydro-3H-pyrazolo(3,4-c)(2,7)-naphthyridin-1-ylamine; D019440:Anti-Obesity Agents; D009287:Naphthyridines; D011720:Pyrazoles; D018004:Receptors, Bombesin; C107120:bombesin receptor subtype 3