Synthesis and biological evaluation of 7-(aminoalkyl)pyrazolo[1,5-a]pyrimidine derivatives as cathepsin K inhibitors |
| |
| Institution: | 1. College of Science, Shenyang University of Chemical Technology, Shenyang 110142, China;2. School of Pharmaceutical Sciences, Liaoning University, Shenyang 110036, China;1. Gokaraju Rangaraju College of Pharmacy, Bachupally, Hyderabad 500090, India;2. Department of Pharmacy, Faculty of Science, National University of Singapore, 18 Science Drive 4, Singapore 117543, Singapore;3. Jadavpur University, Kolkata 700032, India;4. School of Pharmacy, Monash University Sunway Campus, Jalan Lagoon Selatan, Bandar Sunway, Selangor, WA 46150, Malaysia;1. Interdisciplinary Materials Science Program, Vanderbilt University, Nashville, TN 37232, United States;2. Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center, Nashville, TN 37232, United States;3. Center for Molecular Probes, Vanderbilt University Medical Center, Nashville, TN 37232, United States;4. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232, United States;5. Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, United States;6. Vanderbilt-Ingram Cancer Center (VICC), Vanderbilt University Medical Center, Nashville, TN 37232, United States;7. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, United States;8. Department of Chemistry, Vanderbilt University, Nashville, TN 37232, United States;9. Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN 37232, United States |
| |
| Abstract: | A series of novel 7-aminoalkyl substituted pyrazolo1,5-a]pyrimidine derivatives were synthesized and tested for inhibition of cathepsin K. The synthetic methodology comprises cyclization of 5-aminopyrazoles with N-Boc-α-amino acid-derived ynones followed by transformation of the ester and the Boc-amino functions. It allows for easy diversification of the pyrazolo1,5-a]pyrimidine scaffold at various positions. Molecular docking studies with pyrazolo1,5-a]pyrimidine derivatives were also performed to elucidate the binding mode in the active site of cathepsin K. The synthesized compounds exhibited moderate inhibition activity (Ki ≥ 77 μM). |
| |
| Keywords: | Pyrazoles Ynones Cyclisation Cathepsin K Enzyme inhibition Molecular docking |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
