Parallel methods for the preparation and SAR exploration of N-ethyl-4-[(8-alkyl-8-aza-bicyclo[3.2.1]oct-3-ylidene)-aryl-methyl]-benzamides, powerful mu and delta opioid agonists.

Bioorg Med Chem Lett

Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, PO Box 776, Spring House, PA 19477-0776, USA.

Published: November 2004

Two parallel synthetic methods were developed to explore the structure-activity relationships (SAR) of a series of potent opioid agonists. This series of tropanylidene benzamides proved extremely tolerant of structural variation while maintaining excellent opioid activity. Evaluation of several representative compounds from this series in the mouse hot plate test revealed potent antinociceptive effects upon oral administration.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2004.09.004DOI Listing

Publication Analysis

Top Keywords

opioid agonists
8
parallel methods
4
methods preparation
4
preparation sar
4
sar exploration
4
exploration n-ethyl-4-[8-alkyl-8-aza-bicyclo[321]oct-3-ylidene-aryl-methyl]-benzamides
4
n-ethyl-4-[8-alkyl-8-aza-bicyclo[321]oct-3-ylidene-aryl-methyl]-benzamides powerful
4
powerful delta
4
delta opioid
4
agonists parallel
4

Similar Publications

Background: In people with substance use disorders (SUDs), stress-exposure can impair executive function, and increase craving and likelihood of drug-use recurrence. Research shows that acute stressors increase drug-seeking behavior; however, mechanisms underlying this effect are incompletely understood. The Competing Neurobehavioral Decisions System theory posits that persons with SUDs may have hyperactive limbic reward circuitry and hypoactive executive control circuitry.

View Article and Find Full Text PDF

A lipidated peptide derived from the C-terminal tail of the vasopressin 2 receptor shows promise as a new β-arrestin inhibitor.

Pharmacol Res

January 2025

Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada; RECITAL International Partnership Lab, Université de Caen-Normandie, Caen, France & Université de Sherbrooke, Sherbrooke, QC, Canada. Electronic address:

β-arrestins play pivotal roles in seven transmembrane receptor (7TMR) signalling and trafficking. To study their functional role in regulating specific receptor systems, current research relies mainly on genetic tools, as few pharmacological options are available. To address this issue, we designed and synthesised a novel lipidated phosphomimetic peptide inhibitor targeting β-arrestins, called ARIP, which was developed based on the C-terminal tail (A343-S371) of the vasopressin V2 receptor.

View Article and Find Full Text PDF

Background And Purpose: Pituitary adenylate cyclase activating polypeptide (PACAP) is a human migraine trigger that is being targeted for migraine. The δ-opioid receptor (δ-receptor) is a novel target for the treatment of migraine, but its mechanism remains unclear. The goals of this study were to develop a mouse PACAP-headache model using clinically significant doses of PACAP; determine the effects of δ-receptor activation in this model; and investigate the co-expression of δ-receptors, PACAP and PACAP-PAC1 receptor.

View Article and Find Full Text PDF

Examining the association between fentanyl use and perceived adequacy of methadone dose: A retrospective cohort study.

Drug Alcohol Depend

January 2025

British Columbia Centre on Substance Use, 1045 Howe St Suite 400, Vancouver, British Columbia V6Z 2A9, Canada; Interdepartmental Division of Addiction Medicine, St. Paul's Hospital, 1081 Burrard Street, Vancouver, British Columbia, V6Z 1Y6.

Background: People exposed to fentanyl may report that the dose of methadone in the commonly accepted therapeutic range feels too low. We examined self-reported methadone dose adequacy.

Methods: We conducted a retrospective cohort study of individuals prescribed methadone at a dose of at least 60mg daily using data from three community-recruited prospective cohort studies of people who use drugs in Vancouver, Canada from December 2016 through March 2020.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!