University of Oulu

Maksimainen, M., Nurmesjärvi, A., Terho, R., Threadgill, M., Lehtiö, L., Heiskanen, J. (2020) Derivatives of a PARP Inhibitor TIQ-A through the Synthesis of 8-Alkoxythieno[2,3-c]isoquinolin-5(4H)-ones. ACS Omega, 5(22): 13447–13453. https://doi.org/10.1021/acsomega.0c01879

Derivatives of a PARP inhibitor TIQ-A through the synthesis of 8-alkoxythieno[2,3-c]isoquinolin-5(4H)-ones

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Author: Maksimainen, Mirko M.1; Nurmesjärvi, Antti2; Terho, Reima A.2;
Organizations: 1Faculty of Biochemistry and Molecular Medicine & Biocenter Oulu, University of Oulu, Oulu FI-90014, Finland
2Research Unit of Sustainable Chemistry, University of Oulu, P.O. Box 4300, Oulu FI-90014, Finland
3Drug & Target Discovery, Department of Pharmacy & Pharmacology, University of Bath, Bath BA2 7AY, U.K.
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2020060139986
Language: English
Published: American Chemical Society, 2020
Publish Date: 2020-06-01
Description:

Abstract

Thieno[2,3-c]isoquinolin-5(4H)-one is known for its potential as an anti-ischemic agent through the inhibition of poly(ADP-ribose) polymerase 1 (PARP1). However, the compound also inhibits many other enzymes of the PARP family, potentially limiting its usability. The broad inhibition profile, on the other hand, indicates that this molecule backbone could be potentially used as a scaffold for the development of specific inhibitors for certain PARP enzymes. These efforts call for novel synthetic strategies for substituted thieno[2,3-c]isoquinolin-5(4H)-one that could provide the needed selectivity. In this article, an efficient synthetic strategy for 8-alkoxythieno[2,3-c]isoquinolin-5(4H)-ones through eight steps is presented and other tested synthetic pathways are discussed in detail. Synthesis of 7-methoxythieno[2,3-c]isoquinolin-5(4H)-one is also demonstrated to show that the strategy can be applied widely in the syntheses of substituted alkoxythieno[2,3-c]isoquinolin-5(4H)-ones.

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Series: ACS omega
ISSN: 2470-1343
ISSN-E: 2470-1343
ISSN-L: 2470-1343
Volume: 5
Issue: 22
Pages: 13447 - 13453
DOI: 10.1021/acsomega.0c01879
OADOI: https://oadoi.org/10.1021/acsomega.0c01879
Type of Publication: A1 Journal article – refereed
Field of Science: 116 Chemical sciences
Subjects:
Funding: This work was funded by the Academy of Finland (grant nos. 287063 and 294085 for L.L.) and by the Emil Aaltonen Foundation (for M.M.M.).
Academy of Finland Grant Number: 287063
294085
Detailed Information: 287063 (Academy of Finland Funding decision)
294085 (Academy of Finland Funding decision)
Dataset Reference: The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.0c01879.
  https://pubs.acs.org/doi/10.1021/acsomega.0c01879
Copyright information: © 2020 American Chemical Society. This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
  https://creativecommons.org/licenses/by/4.0/