Academic Journal
Subnanomolar Affinity and Selective Antagonism at α7 Nicotinic Receptor by Combined Modifications of 2-Triethylammonium Ethyl Ether of 4-Stilbenol (MG624)
| العنوان: | Subnanomolar Affinity and Selective Antagonism at α7 Nicotinic Receptor by Combined Modifications of 2-Triethylammonium Ethyl Ether of 4-Stilbenol (MG624) |
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| المؤلفون: | F. Bavo, M. Pallavicini, S. Pucci, R. Appiani, A. Giraudo, H. Oh, D. L. Kneisley, B. Eaton, L. Lucero, C. Gotti, F. Clementi, P. Whiteaker, C. Bolchi |
| المساهمون: | F. Bavo, M. Pallavicini, S. Pucci, R. Appiani, A. Giraudo, H. Oh, D.L. Kneisley, B. Eaton, L. Lucero, C. Gotti, F. Clementi, P. Whiteaker, C. Bolchi |
| بيانات النشر: | American Chemical Society |
| سنة النشر: | 2023 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | Settore CHIM/08 - Chimica Farmaceutica, Settore BIO/14 - Farmacologia |
| الوصف: | Modifications of the cationic head and the ethylene linker of 2-(triethylammonium)ethyl ether of 4-stilbenol (MG624) have been proved to produce selective α9*-nAChR antagonism devoid of any effect on the α7-subtype. Here, single structural changes at the styryl portion of MG624 lead to prevailing α7-nAChR antagonism without abolishing α9*-nAChR antagonism. Nevertheless, rigidification of the styryl into an aromatic bicycle, better if including a H-bond donor NH, such as 5-indolyl (31), resulted in higher and more selective α7-nAChR affinity. Hybridization of this modification with the constraint of the 2-triethylammoniumethyloxy portion into (R)-N,N-dimethyl-3-pyrrolidiniumoxy substructure, previously reported as the best modification for the α7-nAChR affinity of MG624 (2), was a winning strategy. The resulting hybrid 33 had a subnanomolar α7-nAChR affinity and was a potent and selective α7-nAChR antagonist, producing at the α7-, but not at the α9*-nAChR, a profound loss of subsequent ACh function. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/36526469; info:eu-repo/semantics/altIdentifier/wos/WOS:000903328600001; volume:66; issue:1; firstpage:306; lastpage:332; numberofpages:27; journal:JOURNAL OF MEDICINAL CHEMISTRY; https://hdl.handle.net/2434/951234; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85144455096 |
| DOI: | 10.1021/acs.jmedchem.2c01256 |
| الاتاحة: | https://hdl.handle.net/2434/951234 https://doi.org/10.1021/acs.jmedchem.2c01256 |
| Rights: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.6D255F15 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acs.jmedchem.2c01256 |
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