Discovery of 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxamides as potent and selective CB2 receptor agonists

The design and synthesis of novel 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxamide CB2 selective ligands for the potential treatment of pain is described. Compound (R,R)-25 has good balance between CB2 agonist potency and selectivity over CB1, and possesses overall favorable pha...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2015-01, Vol.25 (2), p.322-326
Hauptverfasser:	Han, Sangdon, Thoresen, Lars, Zhu, Xiuwen, Narayanan, Sanju, Jung, Jae-Kyu, Strah-Pleynet, Sonja, Decaire, Marc, Choi, Karoline, Xiong, Yifeng, Yue, Dawei, Semple, Graeme, Thatte, Jayant, Solomon, Michelle, Fu, Lixia, Whelan, Kevin, Al-Shamma, Hussien, Gatlin, Joel, Chen, Ruoping, Dang, Huong, Pride, Cameron, Gaidarov, Ibragim, Unett, David J, Behan, Dominic P, Sadeque, Abu, Usmani, Khawja A, Chen, Chuan, Edwards, Jeffrey, Morgan, Michael, Jones, Robert M
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral Analgesics, Non-Narcotic - administration & dosage Analgesics, Non-Narcotic - chemistry Analgesics, Non-Narcotic - pharmacology Animals Arthritis, Experimental - drug therapy Arthritis, Experimental - metabolism Heterocyclic Compounds, 3-Ring - administration & dosage Heterocyclic Compounds, 3-Ring - chemistry Heterocyclic Compounds, 3-Ring - pharmacology Humans Inflammation - drug therapy Inflammation - metabolism Male Microsomes, Liver - drug effects Microsomes, Liver - metabolism Models, Molecular Molecular Structure Osteoarthritis - drug therapy Osteoarthritis - metabolism Pain - drug therapy Pain - metabolism Pyrazoles - administration & dosage Pyrazoles - chemistry Pyrazoles - pharmacology Radioligand Assay Rats Rats, Sprague-Dawley Receptor, Cannabinoid, CB1 - agonists Receptor, Cannabinoid, CB2 - agonists Stereoisomerism Structure-Activity Relationship
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	The design and synthesis of novel 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxamide CB2 selective ligands for the potential treatment of pain is described. Compound (R,R)-25 has good balance between CB2 agonist potency and selectivity over CB1, and possesses overall favorable pharmaceutical properties. It also demonstrated robust in vivo efficacy mediated via CB2 activation in the rodent models of inflammatory and osteoarthritis pain after oral administration.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2014.11.040