Janus kinase 2 inhibitors. Synthesis and characterization of a novel polycyclic azaindole.
The synthesis and characterization of a novel polycyclic azaindole based derivative is disclosed, and its binding to JAK2 is described. The compound is further evaluated for its ability to block the EPO/JAK2 signaling cascade in vitro and in vivo.
Wang
Tiansheng
T
Vertex Pharmaceuticals Inc., Cambridge, Massachusetts 02139-4242, USA.
Duffy
John P
JP
Wang
Jian
J
Halas
Summer
S
Salituro
Francesco G
FG
Pierce
Albert C
AC
Zuccola
Harmon J
HJ
Black
James R
JR
Hogan
James K
JK
Jepson
Scott
S
Shlyakter
Dina
D
Mahajan
Sudipta
S
Gu
Yong
Y
Hoock
Thomas
T
Wood
Mark
M
Furey
Brinley F
BF
Frantz
J Daniel
JD
Dauffenbach
Lisa M
LM
Germann
Ursula A
UA
Fan
Bin
B
Namchuk
Mark
M
Bennani
Youssef L
YL
Ledeboer
Mark W
MW
D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004921:Erythropoietin / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D001372:Aza Compounds; D007211:Indoles; D047029:Lactams, Macrocyclic; D047428:Protein Kinase Inhibitors; D004921:Erythropoietin; D053614:Janus Kinase 2