| Literature DB >> 30608693 |
Yi Zheng1, Samuel Obeng1, Huiqun Wang1, Abdulmajeed M Jali2, Bharath Peddibhotla1, Dwight A Williams1, Chuanchun Zou1, David L Stevens2, William L Dewey2, Hamid I Akbarali2, Dana E Selley2, Yan Zhang1.
Abstract
μ opioid receptor (MOR) agonists have been widely applied for treating moderate to severe pain. However, numerous adverse effects have been associated with their application, including opioid-induced constipation (OIC), respiratory depression, and addiction. On the basis of previous work in our laboratory, NAP, a 6β- N-4'-pyridyl substituted naltrexamine derivative, was identified as a peripheral MOR antagonist that may be used to treat OIC. To further explore its structure-activity relationship, a new series of NAP derivatives were designed, synthesized, and biologically evaluated. Among these derivatives, NFP and NYP significantly antagonized the antinociception effect of morphine. Whereas NAP acted mainly peripherally, its derivatives NFP and NYP actually can act centrally. Furthermore, NFP produced significantly lesser withdrawal symptoms than naloxone at similar doses. These results suggest that NFP has the potential to be a lead compound to treat opioid abuse and addiction.Entities:
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Year: 2019 PMID： 30608693 PMCID： PMC6467700 DOI： 10.1021/acs.jmedchem.8b01158
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446