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Intramolecular Povarov Reactions for the Synthesis of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding to α-Synuclein and Amyloid-β Fibrils
[Image: see text] A BF(3)·OEt(2) catalyzed intramolecular Povarov reaction was used to synthesize 15 chromenopyridine fused thiazolino-2-pyridone peptidomimetics. The reaction works with several O-alkylated salicylaldehydes and amino functionalized thiazolino-2-pyridones, to generate polyheterocycle...
| Autores principales: | , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
American Chemical
Society
2020
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| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660745/ https://www.ncbi.nlm.nih.gov/pubmed/33099999 http://dx.doi.org/10.1021/acs.joc.0c01699 |
| _version_ | 1783609071817981952 |
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| author | Adolfsson, Dan E. Tyagi, Mohit Singh, Pardeep Deuschmann, Adrian Ådén, Jörgen Gharibyan, Anna L. Jayaweera, Sanduni Wasana Lindgren, Anders E. G. Olofsson, Anders Almqvist, Fredrik |
| author_facet | Adolfsson, Dan E. Tyagi, Mohit Singh, Pardeep Deuschmann, Adrian Ådén, Jörgen Gharibyan, Anna L. Jayaweera, Sanduni Wasana Lindgren, Anders E. G. Olofsson, Anders Almqvist, Fredrik |
| author_sort | Adolfsson, Dan E. |
| collection | PubMed |
| description | [Image: see text] A BF(3)·OEt(2) catalyzed intramolecular Povarov reaction was used to synthesize 15 chromenopyridine fused thiazolino-2-pyridone peptidomimetics. The reaction works with several O-alkylated salicylaldehydes and amino functionalized thiazolino-2-pyridones, to generate polyheterocycles with diverse substitution. The synthesized compounds were screened for their ability to bind α-synuclein and amyloid β fibrils in vitro. Analogues substituted with a nitro group bind to mature amyloid fibrils, and the activity moreover depends on the positioning of this functional group. |
| format | Online Article Text |
| id | pubmed-7660745 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | American Chemical
Society |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-76607452020-11-13 Intramolecular Povarov Reactions for the Synthesis of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding to α-Synuclein and Amyloid-β Fibrils Adolfsson, Dan E. Tyagi, Mohit Singh, Pardeep Deuschmann, Adrian Ådén, Jörgen Gharibyan, Anna L. Jayaweera, Sanduni Wasana Lindgren, Anders E. G. Olofsson, Anders Almqvist, Fredrik J Org Chem [Image: see text] A BF(3)·OEt(2) catalyzed intramolecular Povarov reaction was used to synthesize 15 chromenopyridine fused thiazolino-2-pyridone peptidomimetics. The reaction works with several O-alkylated salicylaldehydes and amino functionalized thiazolino-2-pyridones, to generate polyheterocycles with diverse substitution. The synthesized compounds were screened for their ability to bind α-synuclein and amyloid β fibrils in vitro. Analogues substituted with a nitro group bind to mature amyloid fibrils, and the activity moreover depends on the positioning of this functional group. American Chemical Society 2020-10-25 2020-11-06 /pmc/articles/PMC7660745/ /pubmed/33099999 http://dx.doi.org/10.1021/acs.joc.0c01699 Text en © 2020 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
| spellingShingle | Adolfsson, Dan E. Tyagi, Mohit Singh, Pardeep Deuschmann, Adrian Ådén, Jörgen Gharibyan, Anna L. Jayaweera, Sanduni Wasana Lindgren, Anders E. G. Olofsson, Anders Almqvist, Fredrik Intramolecular Povarov Reactions for the Synthesis of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding to α-Synuclein and Amyloid-β Fibrils |
| title | Intramolecular Povarov
Reactions for the Synthesis
of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding
to α-Synuclein and Amyloid-β Fibrils |
| title_full | Intramolecular Povarov
Reactions for the Synthesis
of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding
to α-Synuclein and Amyloid-β Fibrils |
| title_fullStr | Intramolecular Povarov
Reactions for the Synthesis
of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding
to α-Synuclein and Amyloid-β Fibrils |
| title_full_unstemmed | Intramolecular Povarov
Reactions for the Synthesis
of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding
to α-Synuclein and Amyloid-β Fibrils |
| title_short | Intramolecular Povarov
Reactions for the Synthesis
of Chromenopyridine Fused 2-Pyridone Polyheterocycles Binding
to α-Synuclein and Amyloid-β Fibrils |
| title_sort | intramolecular povarov
reactions for the synthesis
of chromenopyridine fused 2-pyridone polyheterocycles binding
to α-synuclein and amyloid-β fibrils |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660745/ https://www.ncbi.nlm.nih.gov/pubmed/33099999 http://dx.doi.org/10.1021/acs.joc.0c01699 |
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