Your browser doesn't support javascript.
loading
Exploring naltrexamine derivatives featuring azaindole moiety via nitrogen-walk approach to investigate their in vitro pharmacological profiles at the mu opioid receptor.
Ma, Hongguang; Wang, Huiqun; Gillespie, James C; Mendez, Rolando E; Selley, Dana E; Zhang, Yan.
Afiliação
  • Ma H; Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, United States.
  • Wang H; Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, United States.
  • Gillespie JC; Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12(th) Street, Richmond, VA 23298, United States.
  • Mendez RE; Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12(th) Street, Richmond, VA 23298, United States.
  • Selley DE; Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12(th) Street, Richmond, VA 23298, United States.
  • Zhang Y; Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 800 E Leigh Street, Richmond, VA 23298, United States. Electronic address: yzhang2@vcu.edu.
Bioorg Med Chem Lett ; 41: 127953, 2021 06 01.
Article em En | MEDLINE | ID: mdl-33766769
In the present work, we reported the application of a nitrogen-walk approach on developing a series of novel opioid ligands containing an azaindole moiety at the C6-position of the epoxymorphinan skeleton. In vitro study results showed that introducing a nitrogen atom around the indole moiety not only retained excellent binding affinity, but also led to significant functional switch at the mu opioid receptor (MOR). Further computational investigations provided corroborative evidence and plausible explanations of the results of the in vitro studies. Overall, our current work implemented a series of novel MOR ligands with high binding affinity and considerably low efficacy, which may shed light on rational design of low efficacy MOR ligands for opioid use disorder therapeutics.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores Opioides mu / Naltrexona / Nitrogênio Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Receptores Opioides mu / Naltrexona / Nitrogênio Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article