Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP)

Standard

Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP). / Safrygin, Alexander ; Zhmurov, Petr ; Dar’in, Dmitry; Silonov, Sergey; Kasatkina, Mariia; Zonis, Yulia; Gureev, Maxim; Krasavin, Mikhail.

In: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 36, No. 1, 2021, p. 1916-1921.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{8e6790cee0c142b9886a328e3280eb44,

title = "Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP)",

abstract = "An earlier described three-component variant of the Castagnoli-Cushman reaction employing homophthalic anhydrides, carbonyl compound and ammonium acetate was applied towards the preparation of 1-oxo-3,4-dihydroisoquinoline-4-carboxamides with variable substituent in position 3. These compounds displayed inhibitory activity towards poly(ADP-ribose) polymerase (PARP), a clinically validated cancer target. The most potent compound (PARP1/2 IC50 = 22/4.0 nM) displayed the highest selectivity towards PARP2 in the series (selectivity index = 5.5), more advantageous ADME prameters compared to the clinically used PARP inhibitor Olaparib.",

keywords = "1-oxo-3,4-dihydroisoquinoline-4-carboxamides, Castagnoli-Cushman reaction, druglikeness, NAD mimetics, PARP1/2 selectivity, poly(ADP-ribose) polymerase, PARP1, 2 selectivity, NAD(+) mimetics, DISCOVERY, 4-dihydroisoquinoline-4-carboxamides, IN-VITRO, 1-oxo-3",

author = "Alexander Safrygin and Petr Zhmurov and Dmitry Dar{\textquoteright}in and Sergey Silonov and Mariia Kasatkina and Yulia Zonis and Maxim Gureev and Mikhail Krasavin",

note = "Publisher Copyright: {\textcopyright} 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.",

year = "2021",

doi = "10.1080/14756366.2021.1969386",

language = "English",

volume = "36",

pages = "1916--1921",

journal = "Journal of Enzyme Inhibition and Medicinal Chemistry",

issn = "1475-6366",

publisher = "Taylor & Francis",

number = "1",

}

RIS

TY - JOUR

T1 - Three-component Castagnoli-Cushman reaction with ammonium acetate delivers 2-unsubstituted isoquinol-1-ones as potent inhibitors of poly(ADP-ribose) polymerase (PARP)

AU - Safrygin, Alexander

AU - Zhmurov, Petr

AU - Dar’in, Dmitry

AU - Silonov, Sergey

AU - Kasatkina, Mariia

AU - Zonis, Yulia

AU - Gureev, Maxim

AU - Krasavin, Mikhail

PY - 2021

Y1 - 2021

N2 - An earlier described three-component variant of the Castagnoli-Cushman reaction employing homophthalic anhydrides, carbonyl compound and ammonium acetate was applied towards the preparation of 1-oxo-3,4-dihydroisoquinoline-4-carboxamides with variable substituent in position 3. These compounds displayed inhibitory activity towards poly(ADP-ribose) polymerase (PARP), a clinically validated cancer target. The most potent compound (PARP1/2 IC50 = 22/4.0 nM) displayed the highest selectivity towards PARP2 in the series (selectivity index = 5.5), more advantageous ADME prameters compared to the clinically used PARP inhibitor Olaparib.

AB - An earlier described three-component variant of the Castagnoli-Cushman reaction employing homophthalic anhydrides, carbonyl compound and ammonium acetate was applied towards the preparation of 1-oxo-3,4-dihydroisoquinoline-4-carboxamides with variable substituent in position 3. These compounds displayed inhibitory activity towards poly(ADP-ribose) polymerase (PARP), a clinically validated cancer target. The most potent compound (PARP1/2 IC50 = 22/4.0 nM) displayed the highest selectivity towards PARP2 in the series (selectivity index = 5.5), more advantageous ADME prameters compared to the clinically used PARP inhibitor Olaparib.

KW - 1-oxo-3,4-dihydroisoquinoline-4-carboxamides

KW - Castagnoli-Cushman reaction

KW - druglikeness

KW - NAD mimetics

KW - PARP1/2 selectivity

KW - poly(ADP-ribose) polymerase

KW - PARP1

KW - 2 selectivity

KW - NAD(+) mimetics

KW - DISCOVERY

KW - 4-dihydroisoquinoline-4-carboxamides

KW - IN-VITRO

KW - 1-oxo-3

UR - http://www.scopus.com/inward/record.url?scp=85113996517&partnerID=8YFLogxK

U2 - 10.1080/14756366.2021.1969386

DO - 10.1080/14756366.2021.1969386

M3 - Article

AN - SCOPUS:85113996517

VL - 36

SP - 1916

EP - 1921

JO - Journal of Enzyme Inhibition and Medicinal Chemistry

JF - Journal of Enzyme Inhibition and Medicinal Chemistry

SN - 1475-6366

IS - 1

ER -

ID: 85382835