Synthesis and biological evaluation of 5-arylamino-6-chloro-1H-indazole-4,7-diones as inhibitors of protein kinase B/Akt.
A series of 5-arylamino-6-chloro-1H-indazole-4,7-diones were synthesized and evaluated for their inhibitory activity on protein kinase B/Akt. The compounds exhibited a potent Akt1 inhibitory activity. Further mechanistic study revealed that they might have dual inhibitory effects on both activity and phosphorylation of Akt1 in PC-3 tumor cell line.
Ko
Jong Hee
JH
ILDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd., 260-5, Eonnam-Dong, Kuseong-Gu, Yongin, Kyongki-Do 449-910, Republic of Korea.
Yeon
Seung Woo
SW
Ryu
Jung Su
JS
Kim
Tae-Yong
TY
Song
Eun-Ha
EH
You
Hea-Jung
HJ
Park
Rae-Eun
RE
Ryu
Chung-Kyu
CK
D000586:Amination; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D002384:Catalysis; D045744:Cell Line, Tumor; D002713:Chlorine / Q000737:chemistry*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D002713:Chlorine; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3