Synthesis of new opioid derivatives with a propellane skeleton and their pharmacologies: Part 5, novel pentacyclic propellane derivatives with a 6-amide side chain.

Journal: Bioorganic & medicinal chemistry

Volume: 23

Issue: 19

Year of Publication: 2016

Affiliated Institutions:  Graduate School of Pure and Applied Sciences, University of Tsukuba, -- Tennodai, Tsukuba, Ibaraki -, Japan. International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, -- Tennodai, Tsukuba, Ibaraki -, Japan. School of Pharmacy, Kitasato University, --, Shirokane, Minato-ku, Tokyo -, Japan. Department of Neuropsychopharmacology, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo -, Japan. Graduate School of Pure and Applied Sciences, University of Tsukuba, -- Tennodai, Tsukuba, Ibaraki -, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, -- Tennodai, Tsukuba, Ibaraki -, Japan. Electronic address: nagase.hiroshi.gt@u.tsukuba.ac.jp.

Abstract summary 

We designed and synthesized pentacyclic propellane derivatives with a 6-amide side chain to afford compounds with higher MOR/KOR ratio and lower sedative effects than nalfurafine. The obtained etheno-bridged derivative with a β-amide side chain, YNT-854, showed a higher MOR/KOR ratio than nalfurafine. YNT-854 also exhibited a higher dose ratio between the sedative effect and the analgesic effect than observed with nalfurafine, which may guide the future design of useful analgesics with a weaker sedative effect than nalfurafine.

Authors & Co-authors:  Nakajima Ryo R Yamamoto Naoshi N Hirayama Shigeto S Iwai Takashi T Saitoh Akiyoshi A Nagumo Yasuyuki Y Fujii Hideaki H Nagase Hiroshi H

Study Outcome 

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Statistics
Citations : 
Authors :  8
Identifiers
Doi : 10.1016/j.bmc.2015.08.036
SSN : 1464-3391
Study Population
Male,Female
Mesh Terms
Amides
Other Terms
Analgesic;KOR selectivity;Nalfurafine;Opioid;Propellane
Study Design
Study Approach
Country of Study
Publication Country
England