475097-54-2Relevant academic research and scientific papers
Discovery of spiro[cyclohexane-dihydropyrano[3,4-b]indole]-amines as potent NOP and opioid receptor agonists
Schunk, Stefan,Linz, Klaus,Frormann, Sven,Hinze, Claudia,Oberb?rsch, Stefan,Sundermann, Bernd,Zemolka, Saskia,Englberger, Werner,Germann, Tieno,Christoph, Thomas,K?gel, Babette-Y.,Schr?der, Wolfgang,Harlfinger, Stephanie,Saunders, Derek,Kless, Achim,Schick, Hans,Sonnenschein, Helmut
, p. 851 - 856 (2014/09/17)
We report the discovery of spiro[cyclohexane-pyrano[3,4-b]indole]-amines, as functional nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonists with strong efficacy in preclinical models of acute and neuropathic pain. Utilizing 4-(dimethylamino)-4-phenylcyclo-hexanone 1 and tryptophol in an oxa-Pictet-Spengler reaction led to the formation of spiroether 2, representing a novel NOP and opioid peptide receptor agonistic chemotype. This finding initially stems from the systematic derivatization of 1, which resulted in alcohols 3-5, ethers 6 and 7, amines 8-10, 22-24, and 26-28, amides 11 and 25, and urea 12, many with low nanomolar binding affinities at the NOP and mu opioid peptide (MOP) receptors.
