Synthesis of biologically active compounds. From chiral amines to protein degraders
Event details
| Date | 30.04.2025 |
| Hour | 17:15 › 18:00 |
| Speaker |
Dr.Antoni Riera Escalé Institut de Recerca Biomèdica (IRB Barcelona) Departament de Química Orgànica Universitat de Barcelona |
| Location |
Salle Unil Genopode A
|
| Category | Conferences - Seminars |
| Event Language | English |
Abstract. The development of a new drug is a very complex and difficult process. It starts with the identification of a biological target (very often a protein) whose biological activity needs to be modified. In most occasions, the way to modify its action is based on the inhibition of its enzymatic activity by a small molecule. To find a good inhibitor is a difficult task but, once achieved, it is necessary to develop an efficient and environmentally benign synthetic procedure. On the other hand, many drugs are chiral and need to be prepared in high enantiomeric purity. Asymmetric hydrogenation is perhaps one of the best methodologies for the large-scale preparation of chiral drugs [1]. We will discuss some of the developments done by our group on the asymmetric hydrogenation of chiral amines, key components of many drugs [2].
In recent years a new pharmacological approach has been developed that might potentially overcome the shortcomings of traditional inhibitors: targeted protein degradation. PROTACs (proteolysis targeting chimeras) are heterobifunctional molecules that hijack the ubiquitin-proteasome system (UPS), native to eukaryotic cells, to induce degradation of a protein of interest (POI) [3]. We will describe the design, synthesis, and optimization of degraders targeting two important proteins: the p38 MAP Kinase [4] and the oestrogen receptor [5].
References:
[1] A. Cabre, X. Verdaguer, A. Riera, Chem. Rev. 122, 269-339 (2022).
[2] a) E. Salomo, S. Orgue, A. Riera, X. Verdaguer, Angew. Chem., Int. Ed. 55, 7988-7992 (2016). b) P. Rojo, M. Molinari, A. Cabre, C. Garcia-Mateos, A. Riera, X. Verdaguer, Angew. Chem., Int. Ed. 61, e202204300 (2022). c) Y. Wen, M. Fernández-Sabaté, A. Lledós, G. Sciortino, J. Eills, I. Marco-Rius, A. Riera, X. Verdaguer, Angew Chem Int Ed Engl, e202404955 (2024).
[3] Li, K.; Crews, C. M. Chem. Soc. Rev., 51, 5214-5236 (2022).
[4] C. Donoghue, M. Cubillos-Rojas, N. Gutierrez-Prat, C. Sanchez-Zarzalejo, X. Verdaguer, A. Riera, A. R. Nebreda, Eur. J. Med. Chem. 2020, 201, 112451.
[5] G. Loren, I. Espuny, A. Llorente, C. Donoghue, X. Verdaguer, R. R. Gomis, A. Riera, Eur. J. Med. Chem. 243, 114770 (2022).
Practical information
- General public
- Free
Organizer
- Prof. N. Cramer
Contact
- Prof. N. Cramer