135350-26-4Relevant articles and documents
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.
A convenient method for the conversion of a carboxy group into a 4,6-dimethoxy-1,3,5-triazine group: Application to N-benzylpyroglutamic acids
Oudir, Souhila,Rigo, Benoit,Henichart, Jean-Pierre,Gautret, Philippe
, p. 2845 - 2848 (2008/02/07)
Reaction of an activated form of carboxylic acids with a stoichiometric amount of zinc dimethyl imidodicarbonimidate (in CH2Cl 2-pyridine with molecular sieves), led to 4,6-dimethoxy-1,3,5- triazines in high yields. This method has b
Studies on Pyrrolidinones. Derivatives of 1,2,3,5,10,10a-Hexahydrobenzindolizine-3,10-dione
Rigo, Benoit,Kolocouris, Nicolas
, p. 893 - 898 (2007/10/02)
The Friedel-Crafts reaction of N-(arylmethyl)-5-pyrrolidinone-2-carboxylic acids gives either a cyclization or a reaction with benzene (used as a solvent).Reactions such as reduction, keto substitution and lactam ring opening of 1,2,3,5,10,10a-hexahydrobe
