title: Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 2: SAR of the amine tether.
abstract: A family of aryl-substituted maleimides was prepared and studied for their activity against calmodulin-dependant kinase. Inhibitory activities against the enzyme ranged from 34nM to >20microM and were dependant upon both the nature of the aryl group and the tether joining the basic amine to the indolyl maleimide core. Key interactions with the kinase ATP site and hinge region, predicted by homology modeling, were confirmed.
authors.affiliation: Scios, Inc., 6500 Paseo Padre Parkway, Fremont, CA 94555, USA. del345@gmail.com
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Levy
authors.forename: Dan-Xiong
authors.initials: DX
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Lu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chen
authors.forename: John
authors.initials: J
authors.lastname: Perumattam
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Xu
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Higaki
authors.forename: Hanmin
authors.initials: H
authors.lastname: Dong
authors.forename: Albert
authors.initials: A
authors.lastname: Liclican
authors.forename: Maureen
authors.initials: M
authors.lastname: Laney
authors.forename: Babu
authors.initials: B
authors.lastname: Mavunkel
authors.forename: Sundeep
authors.initials: S
authors.lastname: Dugar
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008301:Maleimides / Q000138:chemical synthesis / Q000494:pharmacology*; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D000588:Amines; D001555:Benzene Derivatives; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D000255:Adenosine Triphosphate; C517660:CAMK2D protein, human; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2