Discovery and biological evaluation of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor.
A novel series of benzo[a]carbazole-based small molecule agonists of the thrombopoietin (Tpo) receptor is reported. Starting from a 3.4 microM high throughput screen hit, members of this series have been identified which are full agonists with functional potency <50 nM and oral bioavailability in mice.
Alper
Phil B
PB
Genomics Institute of the Novartis Research Foundation (GNF), San Diego, CA 92121, USA.
Marsilje
Thomas H
TH
Mutnick
Daniel
D
Lu
Wenshuo
W
Chatterjee
Arnab
A
Roberts
Michael J
MJ
He
Yun
Y
Karanewsky
Donald S
DS
Chow
Donald
D
Lao
Jianmin
J
Gerken
Andrea
A
Tuntland
Tove
T
Liu
Bo
B
Chang
Jonathan
J
Gordon
Perry
P
Seidel
H Martin
HM
Tian
Shin-Shay
SS
D000284:Administration, Oral; D000818:Animals; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D053628:Receptors, Thrombopoietin / Q000819:agonists* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013926:Thrombopoietin / Q000737:chemistry / Q000378:metabolism
D001555:Benzene Derivatives; D002227:Carbazoles; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin