On the way to selective PARP-2 inhibitors. Design, synthesis, and preliminary evaluation of a series of isoquinolinone derivatives

ChemMedChem
R PellicciariF Moroni

Abstract

PARP-1 and PARP-2 are members of the family of poly(ADP-ribose)polymerases, which are involved in the maintenance of genomic integrity under conditions of genotoxic stimuli. The different roles of the two isoforms under pathophysiological conditions have not yet been fully clarified, and this is partially due to the lack of selective inhibitors. We report herein the synthesis and preliminary pharmacological evaluation of a large series of isoquinolinone derivatives as PARP-1/PARP-2 inhibitors. Among them, we identified the 5-benzoyloxyisoquinolin-1(2 H)-one derivative as the most selective PARP-2 inhibitor reported so far, with a PARP-2/PARP-1 selectivity index greater than 60.

References

Dec 9, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·M EndresM A Moskowitz
Nov 7, 1998·The Journal of Biological Chemistry·W M ShiehE L Jacobson
Jun 11, 1999·The Journal of Biological Chemistry·J C AméG de Murcia
Mar 7, 2002·Trends in Pharmacological Sciences·Alberto Chiarugi
Mar 9, 2004·Progress in Medicinal Chemistry·Roberto PellicciariGabriele Costantino
Jan 27, 2005·Bioorganic & Medicinal Chemistry·Daniele BellocchiRoberto Pellicciari
May 25, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Grazia Graziani, Csaba Szabó
Jun 17, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Julia KoflerRichard J Traystman
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Valérie SchreiberGilbert de Murcia
Sep 2, 2006·The EMBO Journal·José YélamosJosiane Ménissier-de Murcia
Sep 27, 2006·Proceedings of the National Academy of Sciences of the United States of America·Françoise DantzerJosiane Ménissier-de Murcia
Dec 15, 2006·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Silvia FossatiAlberto Chiarugi
Jul 1, 2006·Journal of Natural Medicines·Takafumi NakataniNaoki Noda

❮ Previous
Next ❯

Citations

Sep 4, 2012·Archives of Pharmacal Research·Wei-Qi XuYong-Xiao Cao
Oct 13, 2009·Journal of Combinatorial Chemistry·Sujata RoyRichard C Larock
Apr 21, 2011·Journal of Hematology & Oncology·Yuan YuanHamid R Mirshahidi
Nov 28, 2013·Immunology and Cell Biology·Maria PittelliAlberto Chiarugi
Jun 18, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Roberta FeliciAlberto Chiarugi
May 15, 2012·Cellular and Molecular Life Sciences : CMLS·Magdolna SzántóPéter Bai
Sep 12, 2009·Expert Opinion on Therapeutic Patents·Gianluca PapeoAlessia Montagnoli
Apr 27, 2010·Biochemical Pharmacology·Vincenzo GiansantiA Ivana Scovassi
Jul 15, 2009·Bioorganic & Medicinal Chemistry·Guo-Biao LiuJian-Xin Li
Oct 29, 2015·Chemical Communications : Chem Comm·Ronald GriggNgampong Kongkathip
Apr 18, 2009·British Journal of Pharmacology·Valerie C Besson
Apr 2, 2014·British Journal of Pharmacology·Amos A FatokunTed M Dawson
Jul 14, 2010·Biochimica Et Biophysica Acta·Hanna ShevalyeIrina G Obrosova
Dec 4, 2010·Organic & Biomolecular Chemistry·Peter T SunderlandMichael D Threadgill
May 11, 2016·European Journal of Medicinal Chemistry·Amit NathubhaiMichael D Threadgill
Dec 21, 2016·Future Medicinal Chemistry·Chandan KumarAnnamalai Arunachalam
Sep 1, 2012·CNS Oncology·Ross Carruthers, Anthony J Chalmers
Mar 16, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Joonho ParkJong-In Hong
Jul 4, 2019·Proceedings of the National Academy of Sciences of the United States of America·Bin GuiLi Jia
Feb 8, 2020·Science·Fabian SchneiderTanja Gaich
Feb 9, 2021·Expert Opinion on Therapeutic Patents·Uday Kiran VelagapudiTanaji T Talele
Nov 10, 2018·ACS Omega·Albert A Antolín, Jordi Mestres
Sep 7, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Alexander SafryginMikhail Krasavin

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.