|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
22
|
|
pubmed:dateCreated |
2007-10-16
|
|
pubmed:abstractText |
From HTS lead 1, a novel benzoisoquinolinone class of ATP-competitive Chk1 inhibitors was devised and synthesized via a photochemical route. Using X-ray crystallography as a guide, potency was rapidly enhanced through the installation of a tethered basic amine designed to interact with an acidic residue (Glu91) in the enzyme pocket. Further SAR was explored at the solvent front and near to the H1 pocket and resulted in the discovery of low MW, sub-nanomolar inhibitors of Chk1.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
0960-894X
|
|
pubmed:author |
pubmed-author:AbramsMarc TMT,
pubmed-author:BeckStephen CSC,
pubmed-author:BuserCarolyn ACA,
pubmed-author:DrakasBobB,
pubmed-author:FraleyMark EME,
pubmed-author:GarbaccioRobert MRM,
pubmed-author:HamiltonKelly AKA,
pubmed-author:HardwickJamesJ,
pubmed-author:HartmanGeorge DGD,
pubmed-author:HuangShaeiS,
pubmed-author:IkutaMariM,
pubmed-author:KreatsoulasConstanineC,
pubmed-author:KuoLawrenceL,
pubmed-author:LobellRobR,
pubmed-author:MaoXianzhiX,
pubmed-author:MunshiSanjeevS,
pubmed-author:RickertKeithK,
pubmed-author:Sepp-LorenzinoLauraL,
pubmed-author:StirdivantSteveS,
pubmed-author:TaoWeikangW,
pubmed-author:TasberEdward SES,
pubmed-author:WalshEileen SES,
pubmed-author:YanYouweiY
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
15
|
|
pubmed:volume |
17
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
6280-5
|
|
pubmed:dateRevised |
2011-11-2
|
|
pubmed:meshHeading |
pubmed-meshheading:17900896-Apoptosis,
pubmed-meshheading:17900896-Binding Sites,
pubmed-meshheading:17900896-Cell Line, Tumor,
pubmed-meshheading:17900896-Crystallography, X-Ray,
pubmed-meshheading:17900896-Drug Evaluation, Preclinical,
pubmed-meshheading:17900896-Enzyme Inhibitors,
pubmed-meshheading:17900896-Humans,
pubmed-meshheading:17900896-Inhibitory Concentration 50,
pubmed-meshheading:17900896-Models, Molecular,
pubmed-meshheading:17900896-Molecular Structure,
pubmed-meshheading:17900896-Photochemistry,
pubmed-meshheading:17900896-Protein Kinases,
pubmed-meshheading:17900896-Quinolones,
pubmed-meshheading:17900896-Structure-Activity Relationship
|
|
pubmed:year |
2007
|
|
pubmed:articleTitle |
Synthesis and evaluation of substituted benzoisoquinolinones as potent inhibitors of Chk1 kinase.
|
|
pubmed:affiliation |
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. robert_garbaccio@merck.com
|
|
pubmed:publicationType |
Journal Article
|
