135350-26-4Relevant academic research and scientific papers
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.
Exploiting the regioselectivity of pyroglutamate alkylations for the synthesis of 6-azabicyclo[3.2.1]octanes and 4-azabicyclo[3.3.0]octanes
Masschelein, Kurt G.R.,Stevens, Christian V.,Dieltiens, Nicolai,Claeys, Diederica D.
, p. 4712 - 4724 (2007/10/03)
Depending on the N-protecting group of pyroglutamates, the reactivity can be directed to the formation of 6-azabicyclo[3.2.1]octanes or 4-azabicyclo[3.3.0]octanes, which are conformationally restricted glutamate analogues.
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
Syntheses of 1,2-diamino and 1,2-aminoalcohol derivatives in the piperidine and pyrrolidine series as anti-amnesic agents
Zhao, Shikai,Freeman, Jeremiah P.,Bacon,Fox,O'Driscoll,Foley,Kelly,Farrell,Regan, Ciaran,Mizsak, Stephen A.,Szmuszkovicz, Jacob
, p. 1647 - 1654 (2007/10/03)
Tacrine, one of the drugs available for Alzheimer's disease based on the cholinergic approach, suffers from considerable toxicity. Many analogues of tacrine has been prepared which retain the pharmacologically rich aminopyridine or aminoquinoline motifs. The current research is a continuation of our efforts in the area of 11-aminobenzoquinolizidines (4) and 10-aminobenzoindolizidines (5) (cf. ref 9). A serendipitous discovery led us to the biologically active open chain analogue 9, and we proceeded to elaborate on this molecule. Overall, the compounds we prepared were poor inhibitors of acetylcholinesterase as compared to tacrine. The single exception was compound 20 which exhibited an effect comparable to that of tacrine, but only at a dose in the order of 10-3 M. However, despite the poor acetylcholinesterase inhibition by 9, this compound was found to be an effective antiamnesic agent. Copyright (C) 1999 Elsevier Science Ltd.
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
