Work

Synthesis of 1H-Pyrrolo[3,2-g]isoquinoline Derivatives as Ligands Targeting Haspin Kinase

Year: 2025

Type: article

Abstract: A new series of 1H-pyrrolo[3,2-g]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-g]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.

Source: Molecules

DOI: 10.3390/molecules30224388

Authors: Killian Malosse, Béatrice Josselin, Sandrine Ruchaud, Fabrice Anizon, Francis Giraud, Pascale Moreau