Isoquinoline–pyridine-based protein kinase B/Akt antagonists: SAR and in vivo antitumor activity
摘要:
The structure-activity relationships of a series of isoquinoline-pyridine-based protein kinase B/Akt antagonists have been investigated in an effort to improve the major short-comings of the lead compound 3, including poor pharmacokinetic profiles in several species (e.g., mouse iv t(1/2) = 0.3 h, po F= 0%). Chlorination at C-1 position of the isoquinoline improved its pharmacokinetic property in mice (iv t(1/2) = 5.0 h, po F = 51%) but resulted in > 500-fold drop in potency. In a mouse MiaPaCa-2 xenograft model, an amino analog 10y significantly slowed the tumor growth, however was accompanied by toxicity. (c) 2006 Elsevier Ltd. All rights reserved.
Compounds having the formula
1
are useful for inhibiting protein kinases. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.
3-(PHENYL-ALKOXY)-5-(PHENYL)-PYRIDINE DERIVATIVES AND RELATED COMPOUNDS AS KINASE INHIBITORS FOR THE TREATMENT OF CANCER
申请人:Abbott Laboratories
公开号:EP1463505A2
公开(公告)日:2004-10-06
US6831175B2
申请人:——
公开号:US6831175B2
公开(公告)日:2004-12-14
[EN] KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE
申请人:ABBOTT LAB
公开号:WO2003051366A2
公开(公告)日:2003-06-26
Compounds having the formula (I), are useful for inhibiting protein kinases and for the treatment of cancer. Also disclosed are compositions which inhibit protein kinases and methods of inhibiting protein kinases in a patient.