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Discovery and SAR of 2-aminothiazole inhibitors of cyclin-dependent kinase 5/p25 as a potential treatment for Alzheimer’s disease
- Source :
- Bioorganic & Medicinal Chemistry Letters. 14:5521-5525
- Publication Year :
- 2004
- Publisher :
- Elsevier BV, 2004.
-
Abstract
- High-throughput screening with cyclin-dependent kinase 5 (cdk5)/p25 led to the discovery of N-(5-isopropyl-thiazol-2-yl)isobutyramide (1). This compound is an equipotent inhibitor of cdk5 and cyclin-dependent kinase 2 (cdk2)/cyclin E (IC50 = ca. 320 nM). Parallel and directed synthesis techniques were utilized to explore the SAR of this series. Up to 60-fold improvements in potency at cdk5 and 12-fold selectivity over cdk2 were achieved.
- Subjects :
- Cyclin E
Clinical Biochemistry
Drug Evaluation, Preclinical
Pharmaceutical Science
Nerve Tissue Proteins
Isobutyramide
Pharmacology
Biochemistry
Structure-Activity Relationship
chemistry.chemical_compound
Aminothiazole
Alzheimer Disease
Drug Discovery
CDC2-CDC28 Kinases
Protein kinase A
Molecular Biology
Molecular Structure
biology
Kinase
Cyclin-dependent kinase 5
Cyclin-Dependent Kinase 2
Organic Chemistry
Cyclin-dependent kinase 2
Cyclin-Dependent Kinase 5
Amides
Cyclin-Dependent Kinases
Thiazoles
nervous system
chemistry
Enzyme inhibitor
biology.protein
Molecular Medicine
Subjects
Details
- ISSN :
- 0960894X
- Volume :
- 14
- Database :
- OpenAIRE
- Journal :
- Bioorganic & Medicinal Chemistry Letters
- Accession number :
- edsair.doi.dedup.....f1a7b171a8387e73aea99641b4e26b53