88590-43-6Relevant articles and documents
Resolution and coupling of 1-(2′-hydroxy-1′-naphthyl)isoquinolines
Tucker, Sonia C,Brown, John M,Oakes, John,Thornthwaite, David
, p. 2545 - 2554 (2001)
The synthesis of bridged dimeric isoquinolylnaphthols has been developed. A simple method for the resolution of 1,1′-isoquinolyl-2′-naphthol permits measurement of the optical stability of the monomer, and in several cases slow racemisation at ambient temperature was observed. The enantiomeric stability is not greatly affected by steric buttressing. An unusual enhancement of the rate of atropisomerism is provided by the 3-bromomethylisoquinolines, and undermines the possibility of coupling pure enantiomeric components to provide a single stereoisomer of a tetradentate ligand.
Design, syntheses, and pharmacological characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan analogues as opioid receptor ligands
Yuan, Yunyun,Zaidi, Saheem A.,Stevens, David L.,Scoggins, Krista L.,Mosier, Philip D.,Kellogg, Glen E.,Dewey, William L.,Selley, Dana E.,Zhang, Yan
, p. 1701 - 1715 (2015/03/30)
A series of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan (NAQ) analogues were synthesized and pharmacologically characterized to study their structure-activity relationship at the mu opioid receptor (MOR). The competition binding assay showed two-atom spacer and aromatic side chain were optimal for MOR selectivity. Meanwhile, substitutions at the 1′- and/or 4′-position of the isoquinoline ring retained or improved MOR selectivity over the kappa opioid receptor while still possessing above 20-fold MOR selectivity over the delta opioid receptor. In contrast, substitutions at the 6′- and/or 7′-position of the isoquinoline ring reduced MOR selectivity as well as MOR efficacy. Among this series of ligands, compound 11 acted as an antagonist when challenged with morphine in warm-water tail immersion assay and produced less significant withdrawal symptoms compared to naltrexone in morphine-pelleted mice. Compound 11 also antagonized the intracellular Ca2+ increase induced by DAMGO. Molecular dynamics simulation studies of 11 in three opioid receptors indicated orientation of the 6′-nitro group varied significantly in the different 'address' domains of the receptors and played a crucial role in the observed binding affinities and selectivity. Collectively, the current findings provide valuable insights for future development of NAQ-based MOR selective ligands.
Microwave-assisted synthesis of quinoline, isoquinoline, quinoxaline and quinazoline derivatives as CB2 receptor agonists
Saari, Raimo,T?rm?, Jonna-Carita,Nevalainen, Tapio
experimental part, p. 939 - 950 (2011/03/19)
Quinoline, isoquinoline, quinoxaline, and quinazoline derivatives were synthesized using microwave-assisted synthesis and their CB1/CB2 receptor activities were determined using the [35S]GTPγS binding assay. Most of the prepared quinoline, isoquinoline, and quinoxalinyl phenyl amines showed low-potency partial CB2 receptor agonists activity. The most potent CB2 ligand was the 4-morpholinylmethanone derivative (compound 40e) (-log EC 50 = 7.8; Emax = 75%). The isoquinolin-1-yl(3- trifluoromethyl-phenyl)amine (compound 26c) was a high efficacy CB2 agonist (-log EC50 = 5.8; Emax = 128%). No significant CB1 receptor activation or inactivation was shown in these studies, except 40e, which showed weak CB1 agonist activity (CB1 -log EC50 = 5.0). These ligands serve as novel templates for the development of selective CB2 receptor agonist.
