A novel chemotype of kinase inhibitors: Discovery of 3,4-ring fused 7-azaindoles and deazapurines as potent JAK2 inhibitors.
Pictet-Spengler condensation of aldehydes or alpha-keto-esters with 4-(2-anilinophenyl)-7-azaindole (11) or deazapurine (12) gave high yields of the 3,4-fused cyclic compounds. SAR studies, by varying the substituted benzaldehyde components, lead to the discovery of a series of potent JAK2 kinase inhibitors.
Wang
Tiansheng
T
Vertex Pharmaceuticals Inc., 130 Waverly St., Cambridge, MA 02139-4242, United States. tiansheng_wang@vrtx.com
Ledeboer
Mark W
MW
Duffy
John P
JP
Salituro
Francesco G
FG
Pierce
Albert C
AC
Zuccola
Harmon J
HJ
Block
Eric
E
Shlyakter
Dina
D
Hogan
James K
JK
Bennani
Youssef L
YL
D001547:Benzaldehydes / Q000737:chemistry; D001665:Binding Sites; D002460:Cell Line; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011687:Purines / Q000737:chemistry*; D013329:Structure-Activity Relationship
C023422:7-azaindole dimer; D001547:Benzaldehydes; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011687:Purines; D053614:Janus Kinase 2; C032175:benzaldehyde