Synthesis of 1H-Pyrrolo[3,2-g]isoquinoline Derivatives as Ligands Targeting Haspin Kinase
A new series of 1<i>H</i>-pyrrolo[3,2-<i>g</i>]isoquinolines, diversely substituted at the 3-position either by a heteroaromatic scaffold or by propionate/acrylate side chains, were synthesized and evaluated as Haspin kinase inhibitors. The results of the kinase inhibitory potency study demonstrated that some of the new prepared compounds exhibited low nanomolar potencies toward Haspin. These results indicated that 3-substituted pyrrolo[3,2-<i>g</i>]isoquinolines could serve as intermediates for the development of PROTACs targeting Haspin, with the 3-position allowing further introduction of linkers to tether an E3 ligase ligand. However, this hypothesis remains to be demonstrated.
Authors
- Béatrice Josselin
- Sandrine Ruchaud (ORCID: https://orcid.org/0000-0002-4606-6625)
- F Giraud (ORCID: https://orcid.org/0000-0001-7600-3687)
- Fabrice Anizon (ORCID: https://orcid.org/0000-0001-7869-9622)
- Pascale Moreau (ORCID: https://orcid.org/0000-0001-6527-7586)
- Killian Malosse (ORCID: https://orcid.org/0009-0008-8141-4374)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Clermont Auvergne (FR)
- Station Biologique de Roscoff (FR)
- Sorbonne Université (FR)
- Sigma Clermont (FR)
- Institut de Chimie de Clermont-Ferrand (FR)
- Clermont Université (FR)
Publication Details
- Journal
- Molecules
- Published
- 2025-11-13
- DOI
- https://doi.org/10.3390/molecules30224388
- Primary Topic
- Protein Degradation and Inhibitors
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Alliance Nationale pour les Sciences de la Vie et de la Santé
- Conseil Régional de Bretagne
- Université Clermont-Auvergne