548443-20-5Relevant articles and documents
Synthesis and conformational analysis of phenyl-substituted 1,3,2-oxazaphosphino[4,3-a]- and 1,2,3-oxathiazino[4,3-a]isoquinolines
Schuster, Ildikó,Koch, Andreas,Heydenreich, Matthias,Kleinpeter, Erich,Lázár, László,Fül?p, Ferenc
experimental part, p. 124 - 137 (2009/02/06)
Through the ring closures of tetrahydroisoquinoline 1,3-amino alcohols bearing a phenyl group in the side-chain, diastereomers of novel 1- or 2-phenyl-substituted 1,3,2-oxazaphosphino[4,3-a]isoquinoline 4-oxides, and 1,2,3-oxathiazino[4,3-a]isoquinoline 4-oxides and 4,4-dioxides were prepared. NMR analysis and DFT calculations on the prepared tetrahydroisoquinoline-condensed 1,2,3-heterocycles revealed that their conformational equilibria of cis1-trans-cis2 type are influenced by the relative configuration of P-4 in the 1,3,2-oxazaphosphinanes, and by the position of the phenyl group in the 1,2,3-oxathiazines.
Synthesis and stereochemical studies of 1- and 2-phenyl-substituted 1,3-oxazino[4,3-a]isoquinoline derivatives
Heydenreich, Matthias,Koch, Andreas,Lázár, László,Szatmári, István,Sillanp??, Reijo,Kleinpeter, Erich,Fül?p, Ferenc
, p. 1951 - 1959 (2007/10/03)
Starting from the 1′- or 2′-phenyl-substituted 1-(2′-hydroxyethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline diastereomers 3 and 6, 4-unsubstituted and 4-(p-nitrophenyl)- and 4-oxo-substituted 1-phenyl- and 2-phenyl-9,10-dimethoxy-2H,4H-1,6,7,11b-tetrahydro-1,3-oxazino[4,3- a]isoquinolines (7-12) were prepared. The relative configurations and the predominant conformations of the products were determined by NMR spectroscopy, by quantum chemical calculations and, for (2R*,4S*,11bR*)-9,10-dimethoxy-4-(p-nitrophenyl)-2-phenyl- 2H,4H-1,6,7,11b-tetrahydro-1,3-oxazino[4,3-a]isoquinoline (11), by X-ray diffraction.
Asymmetric synthesis and enantiospecificity of binding of 2-(1,2,3,4-tetrahydro-1-isoquinolyl)-ethanol derivatives to μ and κ receptors
Wanner, Klaus Th.,Praschak, Ilona,Hoefner, Georg,Beer, Herbert
, p. 11 - 22 (2007/10/02)
A number of 2-(1,2,3,4-tetrahydro-1-isoquinolyl)-ethanol derivatives 7a-e have been synthesized in diastereomerically and enantiomerically pure form and have been evaluated for their binding affinity at μ and κ opioid receptors. The amido ketones 5a-c and ent-5a-c, which were accessible by employing 3b and ent-3b for Asymmetric Electrophilic Amidoalkylation reactions, served as starting compounds. Upon reduction of 5a-c and ent-5a-c the amido alcohols l-6a-c, u-6a-c, ent-l-6a-c and ent-u-6a-c were obtained. Hydrolysis of these compounds yielded the secondary amino alcohols l-7a-c, u-7a-c, ent-l-7a-c and ent-u-7a-c and upon reductive methylation of l-7b-c, u-7b-c, ent-l-7b-c and ent-u-7b-c with CH2O and NaCNBH3 the tertiary amino alcohols l-7d-e, u-7d-e, ent-l-7d-e and ent-u-7d-e were obtained. The binding affinities of the final compounds l-7a-e, u-7a-e, ent-l-7a-e and ent-u-7a-e at both the μ and the κ receptor were strongly dependent on their stereochemistry. In each case isomers exhibited higher affinity at the μ than at the κ receptor. For the secondary amino alcohols 7a-c the affinity at the μ receptor followed the stereochemical order l-7 > ent-l-7 > ent-u-7 > u-7 whereas for the tertiary amino alcohols the order l-7 > u-7 > ent-l-7 > ent-u-7 was found. The stereoisomers l-7d and l-7e of the tertiary amino alcohols were found to be the most active compounds the latter exhibiting a K(i) value of 7.17 which is close to that of Morphine (K(i) 1.64). In an in vivo model, the Writhing Test, both compounds l-7d and l-7e displayed high analgetic activity.
