%0 Journal Article %1 Dallanoce2006 %A Dallanoce, C. %A Meroni, G. %A Amici, M. De %A Hoffmann, C. %A Klotz, K. N. %A Micheli, C. De %D 2006 %J Bioorg Med Chem %K Adrenergic Animals CHO Cricetinae Cricetulus Humans Isoxazoles/chemical Stereoisomerism beta-Antagonists/chemical beta/*drug effects synthesis/*chemistry/*pharmacology Receptor Cell %N 13 %P 4393-401 %T Synthesis of enantiopure Delta2-isoxazoline derivatives and evaluation of their affinity and efficacy profiles at human beta-adrenergic receptor subtypes %U http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16530417 %V 14 %X The new enantiomerically pure 3-substituted-Delta(2)-isoxazolin-5-yl-ethanolamines (+)-6a/(-)-6b, (-)-6a/(+)-6b, and (+)-7a/(-)-7b, prepared via a 1,3-dipolar cycloaddition-based approach, were tested for their affinity at human beta(1)-, beta(2)-, and beta(3)-adrenergic receptor (beta-AR) subtypes stably expressed in CHO cells. The corresponding 3-isopropenyl derivatives (+)-5a/(-)-5b, (-)-5a/(+)-5b, and some isoxazole analogs were also tested. The binding affinities at the beta-ARs of the isoxazolinyl amino alcohols were significantly lower than those of the corresponding isoxazole derivatives. A stereochemical effect was observed, since the process of molecular recognition is predominantly controlled by the (S)-configuration of the stereogenic center located at the 5 position of the heterocycle rather than by that of the stereocenter carrying the secondary alcohol group. On the contrary, the stereochemical features marginally affected the efficacy response; as a matter of fact, functional tests carried out on Delta(2)-isoxazoline derivatives provided with a detectable binding affinity showed the overall profile of neutral antagonists at all three beta-AR subtypes.

@article{Dallanoce2006, abstract = {The new enantiomerically pure 3-substituted-Delta(2)-isoxazolin-5-yl-ethanolamines (+)-6a/(-)-6b, (-)-6a/(+)-6b, and (+)-7a/(-)-7b, prepared via a 1,3-dipolar cycloaddition-based approach, were tested for their affinity at human beta(1)-, beta(2)-, and beta(3)-adrenergic receptor (beta-AR) subtypes stably expressed in CHO cells. The corresponding 3-isopropenyl derivatives (+)-5a/(-)-5b, (-)-5a/(+)-5b, and some isoxazole analogs were also tested. The binding affinities at the beta-ARs of the isoxazolinyl amino alcohols were significantly lower than those of the corresponding isoxazole derivatives. A stereochemical effect was observed, since the process of molecular recognition is predominantly controlled by the (S)-configuration of the stereogenic center located at the 5 position of the heterocycle rather than by that of the stereocenter carrying the secondary alcohol group. On the contrary, the stereochemical features marginally affected the efficacy response; as a matter of fact, functional tests carried out on Delta(2)-isoxazoline derivatives provided with a detectable binding affinity showed the overall profile of neutral antagonists at all three beta-AR subtypes.}, added-at = {2010-12-14T18:12:02.000+0100}, author = {Dallanoce, C. and Meroni, G. and Amici, M. De and Hoffmann, C. and Klotz, K. N. and Micheli, C. De}, biburl = {https://www.bibsonomy.org/bibtex/2bc11e0b03fd5644224b24d25ed627f2a/pharmawuerz}, endnotereftype = {Journal Article}, interhash = {fe2b76f5472aee08c0d50222ef7ce315}, intrahash = {bc11e0b03fd5644224b24d25ed627f2a}, issn = {0968-0896 (Print) 0968-0896 (Linking)}, journal = {Bioorg Med Chem}, keywords = {Adrenergic Animals CHO Cricetinae Cricetulus Humans Isoxazoles/chemical Stereoisomerism beta-Antagonists/chemical beta/*drug effects synthesis/*chemistry/*pharmacology Receptor Cell}, month = {Jul 1}, note = {Dallanoce, Clelia Meroni, Giuseppe De Amici, Marco Hoffmann, Carsten Klotz, Karl-Norbert De Micheli, Carlo Research Support, Non-U.S. Gov't England Bioorganic \& medicinal chemistry Bioorg Med Chem. 2006 Jul 1;14(13):4393-401. Epub 2006 Mar 10.}, number = 13, pages = {4393-401}, shorttitle = {Synthesis of enantiopure Delta2-isoxazoline derivatives and evaluation of their affinity and efficacy profiles at human beta-adrenergic receptor subtypes}, timestamp = {2010-12-14T18:22:39.000+0100}, title = {Synthesis of enantiopure Delta2-isoxazoline derivatives and evaluation of their affinity and efficacy profiles at human beta-adrenergic receptor subtypes}, url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16530417}, volume = 14, year = 2006 }