Studies on calpain inhibitors. Synthesis of partially reduced isoquinoline-1-thione derivatives and conversion to functionalized 1-chloroisoquinolines

doi:10.1016/j.tetlet.2008.02.023

Tetrahedron Letters

Volume 49, Issue 14, 31 March 2008, Pages 2275-2279

https://doi.org/10.1016/j.tetlet.2008.02.023 Get rights and content

Abstract

Sequential treatment of a (3-substituted-1-thioxo-1,2,3,4-tetrahydroisoquinolin-4-ylidene)acetic acid with thionyl chloride and a nucleophile did not give the expected ester or amide, but a derivative of 2-(3-substituted-1-chloroisoquinolin-4-yl)acetic acid, constituting a simple procedure for the synthesis of functionalized 1-chloroisoquinolines, which can be useful synthetic intermediates. The different reactivity between lactams and thiolactams has been computationally modelled. The activity as calpain inhibitors of both thiolactams and chloroisoquinoline has been measured, finding that some of these compounds are inhibitors in the micromolar range.

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Acknowledgement

This work was financially supported by Spanish Ministry of Education and Science (Grants CTQ2004-01978 and CTQ2007-64891, and a fellowship to M.A.).

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^☆: Taken in part from the Ph.D. of R.C. (UAM, Madrid, 2007) and the projected Ph.D. of M.A.

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Studies on calpain inhibitors. Synthesis of partially reduced isoquinoline-1-thione derivatives and conversion to functionalized 1-chloroisoquinolines☆

Abstract

Graphical abstract

Section snippets

Acknowledgement

Bioessays

Genome Biol.

Ann. Rev. Pharmacol. Toxicol.

Bull. Soc. Chim. Belg.

Physiol. Rev.

J. Biol. Chem.

Mol. Cell. Biochem.

New Engl. J. Med.

Curr. Opin. Drug Discovery Dev.

Curr. Pharm. Des.

Tetrahedron Lett.

Chem. Biodiv.

Org. Lett.

Bioorg. Med. Chem. Lett.

Eur. J. Org. Chem.

Adv. Synth. Catal.

Heterocycles

ChemMedChem