发明申请
US20160016965A1 NOVEL MIXED μ AGONIST/ δ ANTAGONIST OPIOID ANALGESICS WITH REDUCED TOLERANCE LIABILITIES AND USES THEREOF
有权
新型混合μAGONIST /δANTAGONIST OPIOID ANALGESICS具有降低的容忍负荷及其用途
- 专利标题: NOVEL MIXED μ AGONIST/ δ ANTAGONIST OPIOID ANALGESICS WITH REDUCED TOLERANCE LIABILITIES AND USES THEREOF
- 专利标题(中): 新型混合μAGONIST /δANTAGONIST OPIOID ANALGESICS具有降低的容忍负荷及其用途
-
申请号: US14772592申请日: 2014-03-06
-
公开(公告)号: US20160016965A1公开(公告)日: 2016-01-21
- 发明人: Andrew Coop , Alexander D. Mackerell , Rae Matsumoto
- 申请人: Andrew COOP , Alexander D. MACKERELL , Rae MATSUMOTO
- 申请人地址: US MD Baltimore US WV Morgantown
- 专利权人: UNIVERSITY OF MARYLAND, BALTIMORE,WEST VIRGINIA UNIVERSITY
- 当前专利权人: UNIVERSITY OF MARYLAND, BALTIMORE,WEST VIRGINIA UNIVERSITY
- 当前专利权人地址: US MD Baltimore US WV Morgantown
- 国际申请: PCT/US2014/021155 WO 20140306
- 主分类号: C07D489/08
- IPC分类号: C07D489/08 ; C07D489/02
摘要:
An opioid narcotics used for the treatment of moderate-to-severe pain that primarily exert their analgesic effects through μ receptors. Although, traditional μ agonists can cause undesired side effects, including tolerance, addition of δ antagonists can attenuate said side effects. The present invention includes 4a,9-dihydroxy-7a-(hydroxymethyl)-3-methyl-2,3,4,4a,5,6-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7(7aH)-one (UMB 425) a 5,14-bridged morphinan-based orvinol precursor, along with analogs of morphine, dihydromorphine, hydromorphone, codeine, dihydrocodeine, hydrocodone and ethylmorphine. Although UMB 425 lacks δ-specific motifs, conformationally sampled pharmacophore models for μ and δ receptors predict it to have efficacy similar to morphine at μ receptors and similar to naltrexone at δ receptors, due to the compound sampling conformations in which the hydroxyl moiety interacts with the receptors similar to orvinols. UMB 425 exhibits a mixed μ agonist/δ antagonist profile as determined in receptor binding. UMB 425 has mixed μ agonist/δ antagonist properties in vitro that translate to reduced tolerance liabilities in vivo.
公开/授权文献
信息查询