التفاصيل البيبلوغرافية
| العنوان: |
Design, Synthesis, Evaluation and Structure of Allenic 1α,25-Dihydroxyvitamin D₃ Analogs with Locked Mobility at C-17 |
| المؤلفون: |
Fraga, Ramón, Len, Kateryna, Lutzing, Regis, Laverny, Gilles, Loureiro, Julián, Maestro, Miguel, Rochel, Natacha, Rodríguez-Borges, Enrique, Mouriño, Antonio |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2021 |
| المجموعة: |
RUC - Repositorio Universidade Coruña |
| مصطلحات موضوعية: |
Allenes, Orthoester-Claisen rearrangement, Pd-catalyzed reactions, Synthesis, Vitamin D analogs |
| الوصف: |
[Abstract] Vitamin D receptor ligands have potential for the treatment of hyperproliferative diseases and disorders related to the immune system. However, hypercalcemic effects limit their therapeutical uses and call for the development of tissue-selective new analogs. We have designed and synthesized the first examples of 1α,25-dihydroxyvitamin D₃ analogs bearing an allenic unit attached to the D ring to restrict the side-chain conformational mobility. The triene system was constructed by a Pd⁰-mediated cyclization/Suzuki-Miyaura cross-coupling process in the presence of an allenic side chain. The allenic moiety was built through an orthoester-Claisen rearrangement of a propargylic alcohol. The biological activity and structure of (22S)-1α,25-dihydroxy-17,20-dien-24-homo-21-nor-vitamin D₃ bound to binding domain of the vitamin D receptor, provide information concerning side-chain conformational requirements for biological activity. ; Portugal. Fundação para a Ciência e a Tecnologia; PTDC/BIA-MIB/29059/2017 ; Portugal. Fundação para a Ciência e a Tecnologia; UIDB/50006/2020 ; Xunta de Galicia; ED431B/2018/13 ; Francia. Agence Nationale de la Recherche; ANR-13-BSV8-0024-01 ; Francia. Agence Nationale de la Recherche; ANR-10-LABX-0030-INRT ; Francia. Agence Nationale de la Recherche; ANR-10-IDEX-0002-02 ; Portugal. Fundação para a Ciência e a Tecnologia; SFRH/BSAB/150309/2019 ; Portugal. Fundação para a Ciência e a Tecnologia; PTDC/BIA-MIB/29059 ; Portugal. Fundação para a Ciência e a Tecnologia; 2017-REQUIMTE2019-86 ; We thank FCT of Portugal (project PTDC/BIA-MIB/29059/2017), UIDB/50006/2020 to LAQV-REQUIMTE Research Unit, the European Union (European Regional Development Fund-ERDF), and Xunta de Galicia, Spain (GRC/ED431B/2018/13), for financial support. We also thank the Ligue contre le cancer, Agence Nationale de la Recherche ANR-13-BSV8-0024-01, and institucional funds from Instruct-ERIC for support and use of resources of the French Infrastructure for Integrated Structural Biology (ANR-10-LABX-0030-INRT and ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| تدمد: |
1521-3765 |
| Relation: |
https://doi.org/10.1002/chem.202101578; R. Fraga, K. Len, R. Lutzing, G. Laverny, J. Loureiro, M. A. Maestro, N. Rochel, E. Rodriguez-Borges, A. Mouriño, Design, Synthesis, Evaluation and Structure of Allenic 1α,25-Dihydroxyvitamin D₃ Analogs with Locked Mobility at C-17, Chem. Eur. J. 2021, 27, 13384. DOI:10.1002/chem.202101578; http://hdl.handle.net/2183/28682 |
| الاتاحة: |
http://hdl.handle.net/2183/28682 |
| Rights: |
Atribución-NoComercial-SinDerivadas 4.0 Internacional ; http://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.CDC7B76E |
| قاعدة البيانات: |
BASE |