Copper-Catalyzed Oxidative [3 + 2]-Annulation of Quinoxalin-2(1H)-one with Oxime Esters toward Functionalized Pyrazolo[1,5-a]quinoxalin-4(5H)-ones as Opioid Receptor Modulators
Pyrazolo[1,5-a]quinoxalin-4(5H)-one derivatives as novel opioid receptor modulators have been synthesized via copper-catalyzed oxidative [3 + 2]-annulation of quinoxalin-2(1H)-one and oxime-O-acetates. This hydrazine-free C-C and N-N bond formation strategy starts with the generation of C2N1 synthon using oxime acetate, which reacts in a [3 + 2] manner with quinoxalin-2(1H)-one, followed by oxidative aromatization. The synthesized compounds were tested against opioid receptors, of which eight compounds exhibited an antagonistic effect with EC50 < 5 μM at various opioid receptors. Molecular docking studies were performed to identify the binding of active pyrazolo[1,5-a]quinoxalin-4(5H)-one ligands with hKOR protein. Docking results indicated that compounds 3d and 3g participate in hydrogen bonding with the hydroxyl group of T111 of the active site pocket residue.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:87 |
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| Enthalten in: |
The Journal of organic chemistry - 87(2022), 11 vom: 03. Juni, Seite 7350-7364 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yadav, Anamika [VerfasserIn] |
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| Links: |
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| Themen: |
789U1901C5 |
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| Anmerkungen: |
Date Completed 06.06.2022 Date Revised 24.07.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.joc.2c00563 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM34109918X |
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| 100 | 1 | |a Yadav, Anamika |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Copper-Catalyzed Oxidative [3 + 2]-Annulation of Quinoxalin-2(1H)-one with Oxime Esters toward Functionalized Pyrazolo[1,5-a]quinoxalin-4(5H)-ones as Opioid Receptor Modulators |
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| 500 | |a Date Completed 06.06.2022 | ||
| 500 | |a Date Revised 24.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Pyrazolo[1,5-a]quinoxalin-4(5H)-one derivatives as novel opioid receptor modulators have been synthesized via copper-catalyzed oxidative [3 + 2]-annulation of quinoxalin-2(1H)-one and oxime-O-acetates. This hydrazine-free C-C and N-N bond formation strategy starts with the generation of C2N1 synthon using oxime acetate, which reacts in a [3 + 2] manner with quinoxalin-2(1H)-one, followed by oxidative aromatization. The synthesized compounds were tested against opioid receptors, of which eight compounds exhibited an antagonistic effect with EC50 < 5 μM at various opioid receptors. Molecular docking studies were performed to identify the binding of active pyrazolo[1,5-a]quinoxalin-4(5H)-one ligands with hKOR protein. Docking results indicated that compounds 3d and 3g participate in hydrogen bonding with the hydroxyl group of T111 of the active site pocket residue | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Esters |2 NLM | |
| 650 | 7 | |a Oximes |2 NLM | |
| 650 | 7 | |a Quinoxalines |2 NLM | |
| 650 | 7 | |a Receptors, Opioid |2 NLM | |
| 650 | 7 | |a Copper |2 NLM | |
| 650 | 7 | |a 789U1901C5 |2 NLM | |
| 700 | 1 | |a Yadav, Anubhav |e verfasserin |4 aut | |
| 700 | 1 | |a Tripathi, Shashank |e verfasserin |4 aut | |
| 700 | 1 | |a Dewaker, Varun |e verfasserin |4 aut | |
| 700 | 1 | |a Kant, Ruchir |e verfasserin |4 aut | |
| 700 | 1 | |a Yadav, Prem Narayan |e verfasserin |4 aut | |
| 700 | 1 | |a Srivastava, Ajay Kumar |e verfasserin |4 aut | |
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