Publication Abstract from PubMed
Utilizing structure-based drug design, a 4-aminoimidazole heterocyclic core was synthesized as a replacement for a 2-aminothiazole due to potential metabolically mediated toxicity. The synthetic route utilized allowed for ready synthesis of 1-substituted-4-aminoimidazoles. SAR exploration resulted in the identification of a novel cis-substituted cyclobutyl group that gave improved enzyme and cellular potency against cdk5/p25 with up to 30-fold selectivity over cdk2/cyclin E.
Potent and cellularly active 4-aminoimidazole inhibitors of cyclin-dependent kinase 5/p25 for the treatment of Alzheimer's disease.,Helal CJ, Kang Z, Lucas JC, Gant T, Ahlijanian MK, Schachter JB, Richter KE, Cook JM, Menniti FS, Kelly K, Mente S, Pandit J, Hosea N Bioorg Med Chem Lett. 2009 Oct 1;19(19):5703-7. Epub 2009 Aug 8. PMID:19700321[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
