Bitopic muscarinic agonists and antagonists and uses thereof: a patent evaluation of US20160136145A1.
作者： Ulrike Holzgrabe , Michael Decker
DOI: 10.1080/13543776.2017.1272577
关键词: Receptor 、 Chemistry 、 Acetylcholine 、 Stereochemistry 、 Functional selectivity 、 Muscarinic acetylcholine receptor 、 Neuromuscular Blocking Agents 、 Allosteric regulation 、 Benzoic acid 、 Selectivity
摘要: ABSTRACTIntroduction: Bitopic M ligands, that is, ligands interact both with the ortho- and allosteric binding sites of receptor subtypes, hold great potential as novel selective for muscarinic acetylcholine (M) several therapeutic applications.Areas covered: The patent application describes a set compounds based on neurotransmitter applying Schulman-model comprising heterocyclic (often quaternary) amines benzene ring benzoic acid esters) to act bitopic ligands. claimed functional selectivity are supposed be therapeutically applied neuromuscular blocking agents, in asthma well CNS diseases. In vitro evaluations selected supported some degree was observed - albeit no studies.Expert opinion: quaternary amine structure will prohibit penetration into their ester...
sci-hub.se 参考文章(18)
R Schrage, WK Seemann, J Klöckner, C Dallanoce, K Racké, E Kostenis, M De Amici, U Holzgrabe, K Mohr, Agonists with supraphysiological efficacy at the muscarinic M2 ACh receptor British Journal of Pharmacology. ,vol. 169, pp. 357- 370 ,(2013) , 10.1111/BPH.12003
Celine Valant, Karen J. Gregory, Nathan E. Hall, Peter J. Scammells, Michael J. Lew, Patrick M. Sexton, Arthur Christopoulos, A Novel Mechanism of G Protein-coupled Receptor Functional Selectivity: MUSCARINIC PARTIAL AGONIST McN-A-343 AS A BITOPIC ORTHOSTERIC/ALLOSTERIC LIGAND Journal of Biological Chemistry. ,vol. 283, pp. 29312- 29321 ,(2008) , 10.1074/JBC.M803801200
Andreas Bock, Brian Chirinda, Fabian Krebs, Regina Messerer, Julia Bätz, Mathias Muth, Clelia Dallanoce, Dominika Klingenthal, Christian Tränkle, Carsten Hoffmann, Marco De Amici, Ulrike Holzgrabe, Evi Kostenis, Klaus Mohr, Dynamic ligand binding dictates partial agonism at a G protein–coupled receptor Nature Chemical Biology. ,vol. 10, pp. 18- 20 ,(2014) , 10.1038/NCHEMBIO.1384
Johannes Antony, Kerstin Kellershohn, Marion Mohr‐Andrä, Anna Kebig, Stefanie Prilla, Mathias Muth, Eberhard Heller, Teresa Disingrini, Clelia Dallanoce, Simona Bertoni, Jasmin Schrobang, Christian Trankle, Evi Kostenis, Arthur Christopoulos, Hans‐Dieter Höltje, Elisabetta Barocelli, Marco Amici, Ulrike Holzgrabe, Klaus Mohr, Dualsteric GPCR targeting: a novel route to binding and signaling pathway selectivity The FASEB Journal. ,vol. 23, pp. 442- 450 ,(2009) , 10.1096/FJ.08-114751
Klaus Mohr, Jens Schmitz, Ramona Schrage, Christian Tränkle, Ulrike Holzgrabe, Molecular alliance-from orthosteric and allosteric ligands to dualsteric/bitopic agonists at G protein coupled receptors. Angewandte Chemie. ,vol. 52, pp. 508- 516 ,(2013) , 10.1002/ANIE.201205315
Jessica Klöckner, Ramona Schrage, Evi Kostenis, Christian Tränkle, Gerhard Wolber, Klaus Mohr, Ulrike Holzgrabe, Jens Schmitz, Dorina van der Mey, Marcel Bermudez, Dualsteric muscarinic antagonists--orthosteric binding pose controls allosteric subtype selectivity. Journal of Medicinal Chemistry. ,vol. 57, pp. 6739- 6750 ,(2014) , 10.1021/JM500790X
Chouaib Tahtaoui, Isabelle Parrot, Philippe Klotz, Fabrice Guillier, Jean-Luc Galzi, Marcel Hibert, Brigitte Ilien, Fluorescent pirenzepine derivatives as potential bitopic ligands of the human M1 muscarinic receptor. Journal of Medicinal Chemistry. ,vol. 47, pp. 4300- 4315 ,(2004) , 10.1021/JM040800A
Andreas Bock, Evi Kostenis, Christian Tränkle, Martin J. Lohse, Klaus Mohr, Pilot the pulse: controlling the multiplicity of receptor dynamics. Trends in Pharmacological Sciences. ,vol. 35, pp. 630- 638 ,(2014) , 10.1016/J.TIPS.2014.10.002
Xinyu Chen, Jessika Klöckner, Janine Holze, Cornelia Zimmermann, Wiebke K. Seemann, Ramona Schrage, Andreas Bock, Klaus Mohr, Christian Tränkle, Ulrike Holzgrabe, Michael Decker, Rational Design of Partial Agonists for the Muscarinic M1 Acetylcholine Receptor Journal of Medicinal Chemistry. ,vol. 58, pp. 560- 576 ,(2015) , 10.1021/JM500860W
J. Robert Lane, Patrick M. Sexton, Arthur Christopoulos, Bridging the gap: bitopic ligands of G-protein-coupled receptors. Trends in Pharmacological Sciences. ,vol. 34, pp. 59- 66 ,(2013) , 10.1016/J.TIPS.2012.10.003