A novel approach to cyclin-dependent kinase 5/p25 inhibitors: A potential treatment for Alzheimer’s disease

• Published in: Bioorganic & medicinal chemistry 2007-10, Vol.15 (19), p.6397-6406
• Main Authors: Shiradkar, Mahendra Ramesh, Padhalingappa, Mallikarjuna Bandrehally, Bhetalabhotala, Sastry, Akula, Kalyan Chakravarthy, Tupe, Dattu Anna, Pinninti, Raghotham Reddy, Thummanagoti, Suman
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - pathology; Alzheimer’s disease; Biological and medical sciences; Brain - drug effects; Brain - metabolism; cdk5/p25; Cyclin-Dependent Kinase 5 - antagonists & inhibitors; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Humans; Medical sciences; Microwaves; Nerve Tissue Proteins - antagonists & inhibitors; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - pharmacology; Thienyl; Ticrynafen - chemistry; Triazole
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2007.06.053

The synthesis of a new series of thienyl triazole derivatives under microwave assisted organic synthesis is described. They were tested as cdk5/p25 inhibitors. It was also observed that compounds 4, 5, 7 and 8 from series I while 13, 14, 16 and 17 from series II emerged as significant cdk5/p25 inhibitors. Few compounds were good inhibitors while others were inactive. Based on the earlier results of our in-house database and compound library, a series of novel clubbed thienyl triazoles was designed which may emerge as potential cdk5/p25 inhibitors, for the treatment of Alzheimer’s disease. A benign synthesis was planned so as to take an advantage of MAOS (Microwave Assisted Organic Synthesis) method. Evaluation of the SAR of this series has allowed the identification of compounds 4, 5, 7 and 8 from series I while 13, 14, 16 and 17 from series II as significant cdk5/p25 inhibitors and thus have potential as possible treatments for Alzheimer’s disease.