1613036-99-9Relevant academic research and scientific papers
Design and synthesis of quinolinopropellane derivatives with selective δ opioid receptor agonism
Nagase, Hiroshi,Nakajima, Ryo,Yamamoto, Naoshi,Hirayama, Shigeto,Iwai, Takashi,Nemoto, Toru,Gouda, Hiroaki,Hirono, Shuichi,Fujii, Hideaki
, p. 2851 - 2854 (2014)
Indolopropellane 2 was reported to show almost no binding affinity to the δ opioid receptor (DOR) in spite of the fact that 2 has both the propellane fundamental skeleton (message part) with binding ability to the opioid receptors and a possible DOR address structure (indole moiety). We developed the working hypothesis that almost no binding affinity of 2 to the DOR would be derived from its possibly stable bent conformer. To enable the propellane skeleton to adopt an extended conformation which would reasonably interact with the DOR, quinolinopropellanes 3a-d were designed which had an additional pharmacophore, quinoline nitrogen. The calculated binding free energies of ligand-DOR complexes strongly supported our working hypothesis. The synthesized quinolinopropellane 3a was a selective DOR full agonist, confirming our working hypothesis and the results of in silico investigation.
