Affordable Access

Access to the full text

Structure–Activity Relationships of 7-Substituted Dimethyltyrosine-Tetrahydroisoquinoline Opioid Peptidomimetics

Authors
  • montgomery, deanna
  • anand, jessica p.
  • baber, mason a.
  • twarozynski, jack j.
  • hartman, joshua g.
  • delong, lennon j.
  • traynor, john r.
  • mosberg, henry i.
Publication Date
Nov 26, 2019
Identifiers
DOI: 10.3390/molecules24234302
OAI: oai:mdpi.com:/1420-3049/24/23/4302/
Source
MDPI
Keywords
Language
English
License
Green
External links

Abstract

The opioid receptors modulate a variety of biological functions, including pain, mood, and reward. As a result, opioid ligands are being explored as potential therapeutics for a variety of indications. Multifunctional opioid ligands, which act simultaneously at more than one type of opioid receptor, show promise for use in the treatment of addiction, pain, and other conditions. Previously, we reported the creation of bifunctional kappa opioid receptor (KOR) agonist/mu opioid receptor (MOR) partial agonist ligands from the classically delta opioid receptor (DOR) antagonist selective dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold through the addition of a 7-benzyl pendant on the tetrahydroisoquinoline ring. This study further explores the structure&ndash / activity relationships surrounding 7-position pendants on the Dmt-Tiq scaffold. Some analogues maintain a KOR agonist/MOR partial agonist profile, which is being explored in the development of a treatment for cocaine addiction. Others display a MOR agonist/DOR antagonist profile, which has potential to be used in the creation of a less addictive pain medication. Ultimately, we report the synthesis and in vitro evaluation of novel opioid ligands with a variety of multifunctional profiles.

Report this publication

Statistics

Seen <100 times