Growth vector elaboration of fragments: regioselective functionalization of 5-hydroxy-6-azaindazole and 3-hydroxy-2,6-naphthyridine
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Paulo Eliandro da Silva Junior
- Shaiani Maria Gil de Melo
- Murilo Helder de Paula
- Ricardo Vessecchi
- Till Opatz
- James EH Day
- A Ganesan
- Flavio da Silva Emery
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000853582200001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.1039/d2ob00968d
- eISSN
- 1477-0539
- Externe Identifier
- Clarivate Analytics Document Solution ID: 4X5RD
- PubMed Identifier: 36102876
- ISSN
- 1477-0520
- Ausgabe der Veröffentlichung
- 37
- Zeitschrift
- ORGANIC & BIOMOLECULAR CHEMISTRY
- Paginierung
- 7483 - 7490
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Titel
- Growth vector elaboration of fragments: regioselective functionalization of 5-hydroxy-6-azaindazole and 3-hydroxy-2,6-naphthyridine
- Sub types
- Article
- Ausgabe der Zeitschrift
- 20
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:p>The expansion of the fragment chemical space by accessing growth vectors of two “heteroaromatic rings of the future” with regioselective functionalization is reported.</jats:p>
- Autoren
- Paulo Eliandro da Silva Júnior
- Shaiani Maria Gil de Melo
- Murilo Helder de Paula
- Ricardo Vessecchi
- Till Opatz
- James EH Day
- A Ganesan
- Flavio da Silva Emery
- DOI
- 10.1039/d2ob00968d
- eISSN
- 1477-0539
- ISSN
- 1477-0520
- Ausgabe der Veröffentlichung
- 37
- Zeitschrift
- Organic & Biomolecular Chemistry
- Sprache
- en
- Online publication date
- 2022
- Paginierung
- 7483 - 7490
- Status
- Published online
- Herausgeber
- Royal Society of Chemistry (RSC)
- Herausgeber URL
- http://dx.doi.org/10.1039/d2ob00968d
- Datum der Datenerfassung
- 2024
- Titel
- Growth vector elaboration of fragments: regioselective functionalization of 5-hydroxy-6-azaindazole and 3-hydroxy-2,6-naphthyridine
- Ausgabe der Zeitschrift
- 20
Datenquelle: Crossref
- Abstract
- This article discusses the reactivity of 6-azaindazole (1) and 2,6-naphthyridine (2), proposed to be "heteroaromatic rings of the future," which would be useful for fragment-based drug discovery (FBDD) campaigns, developing growth vectors for fragment elaboration by selectively functionalizing different positions on the rings. The pyridone oxygens and pyrazole nitrogen can be functionalized selectively. Arylation at the α-carbon of the pyridone moiety was achieved by a transition metal-free radical cross-coupling using aryl hydrazines. This method proceeded under mild conditions without the need for protection of the hydroxypyridine. Additionally, we developed a method for the regioselective C-3 functionalization of heterocycle 1<i>via N</i>-sulfonamide rearrangement. This method involved a novel regioselective base-mediated N-C migration of the N-1 sulfonamide to yield the C-3 sulfone. This procedure is also applicable for indazole C-3 functionalization and mechanistic studies of the rearrangement suggest that an intermolecular process is involved. These reactions enable the fragment elaboration of heterocycles 1 and 2 in several growth vectors to facilitate their use in FBDD.
- Addresses
- Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Departmento de Ciências Farmacêuticas, Universidade de São Paulo, Ribeirão Preto 14040-903, Brazil. flavioemery@usp.br.
- Autoren
- Paulo Eliandro da Silva Júnior
- Shaiani Maria Gil de Melo
- Murilo Helder de Paula
- Ricardo Vessecchi
- Till Opatz
- James EH Day
- A Ganesan
- Flavio da Silva Emery
- DOI
- 10.1039/d2ob00968d
- eISSN
- 1477-0539
- Externe Identifier
- PubMed Identifier: 36102876
- Funding acknowledgements
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior: SVR 119/2012
- Fundação de Amparo à Pesquisa do Estado de São Paulo: #2017/21146-6
- Conselho Nacional de Desenvolvimento Científico e Tecnológico: 313834/2018-0
- Conselho Nacional de Desenvolvimento Científico e Tecnológico: 428527/2016-7
- Fundação de Amparo à Pesquisa do Estado de São Paulo: #2013/26485-0
- Fundação de Amparo à Pesquisa do Estado de São Paulo: #2016/24817-4
- Astex Pharmaceuticals:
- Open access
- false
- ISSN
- 1477-0520
- Ausgabe der Veröffentlichung
- 37
- Zeitschrift
- Organic & biomolecular chemistry
- Schlüsselwörter
- Carbon
- Nitrogen
- Sulfonamides
- Hydrazines
- Sulfones
- Pyrazoles
- Indazoles
- Pyridones
- Naphthyridines
- Catalysis
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2022
- Paginierung
- 7483 - 7490
- Datum der Veröffentlichung
- 2022
- Status
- Published
- Datum der Datenerfassung
- 2022
- Titel
- Growth vector elaboration of fragments: regioselective functionalization of 5-hydroxy-6-azaindazole and 3-hydroxy-2,6-naphthyridine.
- Sub types
- Research Support, Non-U.S. Gov't
- Journal Article
- Ausgabe der Zeitschrift
- 20
Datenquelle: Europe PubMed Central
- Abstract
- This article discusses the reactivity of 6-azaindazole (1) and 2,6-naphthyridine (2), proposed to be "heteroaromatic rings of the future," which would be useful for fragment-based drug discovery (FBDD) campaigns, developing growth vectors for fragment elaboration by selectively functionalizing different positions on the rings. The pyridone oxygens and pyrazole nitrogen can be functionalized selectively. Arylation at the α-carbon of the pyridone moiety was achieved by a transition metal-free radical cross-coupling using aryl hydrazines. This method proceeded under mild conditions without the need for protection of the hydroxypyridine. Additionally, we developed a method for the regioselective C-3 functionalization of heterocycle 1via N-sulfonamide rearrangement. This method involved a novel regioselective base-mediated N-C migration of the N-1 sulfonamide to yield the C-3 sulfone. This procedure is also applicable for indazole C-3 functionalization and mechanistic studies of the rearrangement suggest that an intermolecular process is involved. These reactions enable the fragment elaboration of heterocycles 1 and 2 in several growth vectors to facilitate their use in FBDD.
- Autoren
- Paulo Eliandro da Silva Júnior
- Shaiani Maria Gil de Melo
- Murilo Helder de Paula
- Ricardo Vessecchi
- Till Opatz
- James EH Day
- A Ganesan
- Flavio da Silva Emery
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/36102876
- DOI
- 10.1039/d2ob00968d
- eISSN
- 1477-0539
- Ausgabe der Veröffentlichung
- 37
- Zeitschrift
- Org Biomol Chem
- Schlüsselwörter
- Carbon
- Catalysis
- Hydrazines
- Indazoles
- Naphthyridines
- Nitrogen
- Pyrazoles
- Pyridones
- Sulfonamides
- Sulfones
- Sprache
- eng
- Country
- England
- Paginierung
- 7483 - 7490
- Datum der Veröffentlichung
- 2022
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2022
- Titel
- Growth vector elaboration of fragments: regioselective functionalization of 5-hydroxy-6-azaindazole and 3-hydroxy-2,6-naphthyridine.
- Sub types
- Journal Article
- Research Support, Non-U.S. Gov't
- Ausgabe der Zeitschrift
- 20
Datenquelle: PubMed
- Beziehungen:
- Eigentum von