2-((Dimethylamino)methyl)-9-hydroxythieno[2,3-c]isoquinolin-5(4H)-one (HYDAMTIQ), a potent PARP1/2 inhibitor, is currently being evaluated in preclinical trials for the treatment of ischemia and inflammatory diseases. The current batch synthesis, which includes a Suzuki-Miyaura reaction, a thermal cyclization, and a Mannich-type reaction, makes it a challenging target to prepare on a multigram scale and support compound development. Herein, a telescoped continuous flow synthesis of the key thieno[2,3-c]isoquinolin-5(4H)-one scaffold and much improved chromatography-free, downstream steps for HYDAMTIQ have been developed. Assessment of quantitative green metrics confirms the improved efficiency and sustainability of the newly developed flow route, providing a straightforward and versatile approach for scale-up and medicinal chemistry investigations.

Continuous Flow Synthesis of the PARP-1/2 Inhibitor HYDAMTIQ: Synthetic Strategy, Optimization, and Green Metrics Evaluation

Filipponi, Paolo;Cerra, Bruno;Piccinno, Alessandro;Camaioni, Emidio;Gioiello, Antimo
2023

Abstract

2-((Dimethylamino)methyl)-9-hydroxythieno[2,3-c]isoquinolin-5(4H)-one (HYDAMTIQ), a potent PARP1/2 inhibitor, is currently being evaluated in preclinical trials for the treatment of ischemia and inflammatory diseases. The current batch synthesis, which includes a Suzuki-Miyaura reaction, a thermal cyclization, and a Mannich-type reaction, makes it a challenging target to prepare on a multigram scale and support compound development. Herein, a telescoped continuous flow synthesis of the key thieno[2,3-c]isoquinolin-5(4H)-one scaffold and much improved chromatography-free, downstream steps for HYDAMTIQ have been developed. Assessment of quantitative green metrics confirms the improved efficiency and sustainability of the newly developed flow route, providing a straightforward and versatile approach for scale-up and medicinal chemistry investigations.
2023
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/1563875
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 2
  • ???jsp.display-item.citation.isi??? ND
social impact