Design and Synthesis of 7-(N-Aryl Pyrrolidinyl) Indoles as Potential DCAF15 Binders
We describe the design and synthesis of a series of 7-(N-aryl pyrrolidinyl) indoles and oxo-analogs as isosteric mimics of the DCAF15 binder E7820, a well-known member of aryl sulfonamides known as SPLAMs. The functionalization of C-7 in indoles was achieved by metal-catalyzed CH-activation with une...
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| Format: | Article |
| Language: | English |
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MDPI AG
2025-03-01
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| Online Access: | https://www.mdpi.com/2624-781X/6/1/20 |
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| author | Ravi Devarajappa Scarlett Kiyeleko Sofiane Hocine Victor Cosson Remi Calandrino Timea Baló Jayson Alves Bordelo Sébastien Triboulet Laure Caruana Laurence Klipfel Sandrine Calis András Herner Stephen Hanessian |
| author_facet | Ravi Devarajappa Scarlett Kiyeleko Sofiane Hocine Victor Cosson Remi Calandrino Timea Baló Jayson Alves Bordelo Sébastien Triboulet Laure Caruana Laurence Klipfel Sandrine Calis András Herner Stephen Hanessian |
| author_sort | Ravi Devarajappa |
| collection | DOAJ |
| description | We describe the design and synthesis of a series of 7-(N-aryl pyrrolidinyl) indoles and oxo-analogs as isosteric mimics of the DCAF15 binder E7820, a well-known member of aryl sulfonamides known as SPLAMs. The functionalization of C-7 in indoles was achieved by metal-catalyzed CH-activation with unexpected results. Binding assays revealed the pyrrolidine N-aryl carboxylic acid analog to be as equally active as E7820. |
| format | Article |
| id | doaj-art-a80c566c05cc4f169cdf9cd20d83b225 |
| institution | DOAJ |
| issn | 2624-781X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Reactions |
| spelling | doaj-art-a80c566c05cc4f169cdf9cd20d83b2252025-08-20T02:43:06ZengMDPI AGReactions2624-781X2025-03-01612010.3390/reactions6010020Design and Synthesis of 7-(N-Aryl Pyrrolidinyl) Indoles as Potential DCAF15 BindersRavi Devarajappa0Scarlett Kiyeleko1Sofiane Hocine2Victor Cosson3Remi Calandrino4Timea Baló5Jayson Alves Bordelo6Sébastien Triboulet7Laure Caruana8Laurence Klipfel9Sandrine Calis10András Herner11Stephen Hanessian12Department of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC H3C 3J7, CanadaDepartment of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC H3C 3J7, CanadaDepartment of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC H3C 3J7, CanadaDepartment of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC H3C 3J7, CanadaDepartment of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC H3C 3J7, CanadaServier Research Institute of Medicinal Chemistry Záhony u. 7., H-1031 Budapest, HungaryInstitut de Recherches Servier, 22 Route 128, 91190 Gif-sur-Yvette, FranceInstitut de Recherches Servier, 22 Route 128, 91190 Gif-sur-Yvette, FranceInstitut de Recherches Servier, 22 Route 128, 91190 Gif-sur-Yvette, FranceInstitut de Recherches Servier, 22 Route 128, 91190 Gif-sur-Yvette, FranceInstitut de Recherches Servier, 22 Route 128, 91190 Gif-sur-Yvette, FranceServier Research Institute of Medicinal Chemistry Záhony u. 7., H-1031 Budapest, HungaryDepartment of Chemistry, Université de Montréal, Station Centre-Ville, C.P. 6128, Montreal, QC H3C 3J7, CanadaWe describe the design and synthesis of a series of 7-(N-aryl pyrrolidinyl) indoles and oxo-analogs as isosteric mimics of the DCAF15 binder E7820, a well-known member of aryl sulfonamides known as SPLAMs. The functionalization of C-7 in indoles was achieved by metal-catalyzed CH-activation with unexpected results. Binding assays revealed the pyrrolidine N-aryl carboxylic acid analog to be as equally active as E7820.https://www.mdpi.com/2624-781X/6/1/20molecular gluesDCAF15 bindersindole derivatives |
| spellingShingle | Ravi Devarajappa Scarlett Kiyeleko Sofiane Hocine Victor Cosson Remi Calandrino Timea Baló Jayson Alves Bordelo Sébastien Triboulet Laure Caruana Laurence Klipfel Sandrine Calis András Herner Stephen Hanessian Design and Synthesis of 7-(N-Aryl Pyrrolidinyl) Indoles as Potential DCAF15 Binders Reactions molecular glues DCAF15 binders indole derivatives |
| title | Design and Synthesis of 7-(N-Aryl Pyrrolidinyl) Indoles as Potential DCAF15 Binders |
| title_full | Design and Synthesis of 7-(N-Aryl Pyrrolidinyl) Indoles as Potential DCAF15 Binders |
| title_fullStr | Design and Synthesis of 7-(N-Aryl Pyrrolidinyl) Indoles as Potential DCAF15 Binders |
| title_full_unstemmed | Design and Synthesis of 7-(N-Aryl Pyrrolidinyl) Indoles as Potential DCAF15 Binders |
| title_short | Design and Synthesis of 7-(N-Aryl Pyrrolidinyl) Indoles as Potential DCAF15 Binders |
| title_sort | design and synthesis of 7 n aryl pyrrolidinyl indoles as potential dcaf15 binders |
| topic | molecular glues DCAF15 binders indole derivatives |
| url | https://www.mdpi.com/2624-781X/6/1/20 |
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