Enabling, Decagram-Scale Synthesis of Macrocyclic MCL-1 Inhibitor ABBV-467
ABBV-467 is a highly potent and selective MCL-1 inhibitor that was advanced to a phase I clinical trial for the treatment of multiple myeloma. Due to its large size and structural complexity, ABBV-467 is a challenging synthetic target. Herein, we describe the synthesis of ABBV-467 on a decagram scale, which enabled preclinical characterization. The strategy is convergent and stereoselective, featuring a hindered biaryl cross coupling, enantioselective hydrogenation, and conformationally preorganized macrocyclization by C-O bond formation as key steps.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:88 |
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| Enthalten in: |
The Journal of organic chemistry - 88(2023), 22 vom: 17. Nov., Seite 15562-15568 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Brady, Patrick B [VerfasserIn] |
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| Links: |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 20.11.2023 Date Revised 21.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.joc.3c00939 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364017600 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ABBV-467 is a highly potent and selective MCL-1 inhibitor that was advanced to a phase I clinical trial for the treatment of multiple myeloma. Due to its large size and structural complexity, ABBV-467 is a challenging synthetic target. Herein, we describe the synthesis of ABBV-467 on a decagram scale, which enabled preclinical characterization. The strategy is convergent and stereoselective, featuring a hindered biaryl cross coupling, enantioselective hydrogenation, and conformationally preorganized macrocyclization by C-O bond formation as key steps | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Myeloid Cell Leukemia Sequence 1 Protein |2 NLM | |
| 700 | 1 | |a Sorensen, Bryan K |e verfasserin |4 aut | |
| 700 | 1 | |a Risi, Roberto M |e verfasserin |4 aut | |
| 700 | 1 | |a Curtin, Michael L |e verfasserin |4 aut | |
| 700 | 1 | |a Mantei, Robert A |e verfasserin |4 aut | |
| 700 | 1 | |a Florjancic, Alan S |e verfasserin |4 aut | |
| 700 | 1 | |a Mastracchio, Anthony |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Kunzer, Aaron R |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Chunqiu |e verfasserin |4 aut | |
| 700 | 1 | |a Storer, Gregory E |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Vincent S |e verfasserin |4 aut | |
| 700 | 1 | |a Henry, Rodger F |e verfasserin |4 aut | |
| 700 | 1 | |a Souers, Andrew J |e verfasserin |4 aut | |
| 700 | 1 | |a Michaelides, Michael R |e verfasserin |4 aut | |
| 700 | 1 | |a Judd, Andrew S |e verfasserin |4 aut | |
| 700 | 1 | |a Hansen, T Matthew |e verfasserin |4 aut | |
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