244622-23-9Relevant academic research and scientific papers
Synthesis of an o-nitrobenzyl attached A1 adenosine receptor antagonist, a prodrug approach
Chang, HeXi,Ensinger, Carol,McCargar, Robert D.,Vittimberga, Bruno M.
, p. 2605 - 2611 (2007/10/03)
The o-nitrobenzyl group, possessing distinct advantage of being photolabile under mild conditions, was successfully connected to 8-(5,6-epoxynorbornan-2-yl)-1,3-dipropylxanthine (5), a high specific A1 adenosine receptor antagonist. The resulting compound 4 would have potential use as a prodrug.
Synthesis and biological evaluation of the enantiomers of the potent and selective A1-adenosine antagonist 1,3-dipropyl-8-[2-(5,6-epoxynorbonyl)]- xanthine
Pfister, Jürg R.,Belardinelli, Luiz,Lee, Gavin,Lum, Robert T.,Milner, Peter,Stanley, William C.,Linden, Joel,Baker, Stephen P.,Schreiner, George
, p. 1773 - 1778 (2007/10/03)
The individual enantiomers 8 and 12 of the potent and highly selective racemic A1-adenosine antagonist 1,3-dipropyl-8-[2-(5,6- epoxynorbornyl)]xanthine (ENX, 4) were synthesized utilizing asymmetric Diels-Alder cycloadditions for the construction of the norbornane moieties. The absolute configuration of 12 was determined by X-ray crystallography of the 4-bromobenzoate 14, which was derived from the bridged secondary alcohol 13. The latter was obtained from 12 by an acid-catalyzed intramolecular rearrangement. The binding affinities of the enantiomers 8 and 12 and the racemate 4 at guinea pig, rat, and cloned human A1- and A(2a)-adenosine receptor subtypes were determined. The S-enantiomer 12 (CVT-124) appears to be one of the more potent and clearly the most A1-selective antagonist reported to date, with K(i) values of 0.67 and 0.45 nM, respectively, at the rat and cloned human A1-receptors and with 1800-fold (rat) and 2400-fold (human) subtype selectivity. Both enantiomers, administered intravenously to saline-loaded rats, induced diuresis via antagonism of renal A1-adenosine receptors.
The use of 1-amino-2-phenyl-1-cyclohexanecarboxylic acids as chiral auxiliaries in asymmetric Diels-Alder reactions
Avenoza, Alberto,Cativiela, Carlos,Paris, Miguel,Peregrina, Jesus M.
, p. 4839 - 4848 (2007/10/03)
This report describes the behavior of four 1-amino-2-phenyl-1-cyclohexanecarboxylic acids, obtained in enantiomerically pure form starting from asymmetric Diels-Alder reactions between 1,3-butadiene and chiral (E)-2-cyanocinnamates, as chiral auxiliaries in the asymmetric Diels-Alder reactions of cyclopentadiene with chiral methyl N-acryloyl-1-amino-2-phenyl-1-cyclohexane-carboxylates. A model based on the formation of an intramolecular hydrogen bond accounts for the stereochemical outcome in the catalyzed reactions.
