Type
Text
Type
Thesis
Advisor
Ojima, Iwao | Sampson, Nicole. | Lauher, Joseph
Date
2017-05-01
Keywords
anandamide, fatty acid binding protein, inhibitor, truxillic acid | Chemistry
Department
Department of Chemistry
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/77048
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
Pain management has become a major issue in health care. It has been reported that about 100 million Americans are affected by chronic pain, and it costs us about $600 million per year. Current drugs used in pain management such as opioids, and marijuana have some unwanted side effects. Thus, there is a need to explore and develop novel, safer and more effective drugs for pain relief. Anandamide (AEA) is an endocannabinoid, and it can activate cannabinoid(CB) receptors on the cell surface, resulting in pain relief. However, AEA can also diffuse into cells, transported by fatty acid binding proteins (FABPs) to fatty acid amide hydrolase (FAAH) where AEA is hydrolyzed. FABP inhibitors can block the pathway for AEA to be inactivated, resulting in enhancement of the pathway to relief pain. Our interdisciplinary research team has determined the co-crystal structures of FABP5 and FABP7 with our previous lead compound SB-FI-26. Based on the co-crystal structure of the FABP5-SB-FI-26, new SB-FI-26 analogues have been designed and synthesized to optimize potency. The design and synthesis of alpha-truxillic acid derivatives, as well as their biological evaluations will be presented. In addition, the synthesis of novel matrix metalloproteinase (MMP) 9 inhibitors will also be presented. | 74 pages
Recommended Citation
Qianwen, Gan, "Design and Synthesis of Alpha-Truxillic Acid-Based Fatty Acid Binding Proteins Inhibitors" (2017). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2891.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2891