New effective inhibitors of the Abelson kinase


Publication Type:

Journal Article


Bioorganic & Medicinal Chemistry, Volume 18, Number 17, p.6316-21 (2010)


1464-3391 (Electronic)<br/>0968-0896 (Linking)

Accession Number:



Benzamides, Fusion Proteins, bcr-abl/*antagonists & inhibitors, Humans, Piperazines/chemistry/pharmacology, Protein Kinase Inhibitors/chemistry/*pharmacology, Proto-Oncogene Proteins c-abl/*antagonists & inhibitors, Pyridones/chemistry/pharmacology, Pyrimidines/chemistry/pharmacology, Structure-Activity Relationship


<p>The effects of substituents on the aryl ring were studied by the preparation and testing of several PD173955 analogs. Inserting a single carbon atom into the C-N bond in the aniline subunit (PDC) reduced the kinase inhibition by a factor of 200. Despite its decreased affinity for Abl compared with PD173955, PDC exhibits a Ki very similar to that reported for Imatinib. Increased water solubility is also gained by replacing the thiomethyl group with an amino or glycyl moiety. For both PD173955 and PDC, the analogs with amino groups in place of the methylthio group are 10 times more inhibitory than the parent molecules. Two molecules were identified with Kis about three orders of magnitude lower than reported for Imatinib.</p>


Kraus, George A<br/>Gupta, Vinayak<br/>Mokhtarian, Marjan<br/>Mehanovic, Samir<br/>Nilsen-Hamilton, Marit<br/>P01 ES012020/ES/NIEHS NIH HHS/<br/>R43CA-110222/CA/NCI NIH HHS/<br/>England<br/>Bioorg Med Chem. 2010 Sep 1;18(17):6316-21. doi: 10.1016/j.bmc.2010.07.021. Epub 2010 Jul 14.