Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 4. Identification of New Potent and Selective Ligands for the Cannabinoid Type 2 Receptor with Diverse Substitution Patterns and Antihyperalg
详细信息 查看全文
- 作者：Serena Pasquini ; Maria De Rosa ; Valentina Pedani ; Claudia Mugnaini ; Francesca Guida ; Livio Luongo ; Maria De Chiaro ; Sabatino Maione ; Stefania Dragoni ; Maria Frosini ; Alessia Ligresti ; Vincenzo Di Marzo ; Federico Corelli
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：August 11, 2011
- 年：2011
- 卷：54
- 期：15
- 页码：5444-5453
- 全文大小：1130K
- 年卷期：v.54,no.15(August 11, 2011)
- ISSN：1520-4804
文摘
Experimental evidence suggests that selective CB2 receptor modulators may provide access to antihyperalgesic agents devoid of psychotropic effects. Taking advantage of previous findings on structure鈥揳ctivity/selectivity relationships for a class of 4-quinolone-3-carboxamides, further structural modifications of the heterocyclic scaffold were explored, leading to the discovery of the 8-methoxy derivative 4a endowed with the highest affinity and selectivity ever reported for a CB2 ligand. The compound, evaluated in vivo in the formalin test, behaved as an inverse agonist by reducing at a dose of 6 mg/kg the second phase of the formalin-induced nocifensive response in mice.