Johannes, Jeffrey W.; Balazs, Amber; Barratt, Derek; Bista, Michal; Chuba, Matthew D.; Cosulich, Sabina; Critchlow, Susan E.; Degorce, Sebastien L.; Di Fruscia, Paolo; Edmondson, Scott D.; Embrey, Kevin; Fawell, Stephen; Ghosh, Avipsa; Gill, Sonja J.; Gunnarsson, Anders; Hande, Sudhir M.; Heightman, Tom D.; Hemsley, Paul; Illuzzi, Giuditta; Lane, Jordan; Larner, Carrie; Leo, Elisabetta; Liu, Lina; Madin, Andrew; Martin, Scott; McWilliams, Lisa; O′Connor, Mark J.; Orme, Jonathan P.; Pachl, Fiona; Packer, Martin J.; Pei, Xiaohui; Pike, Andrew; Schimpl, Marianne; She, Hongyao; Staniszewska, Anna D.; Talbot, Verity; Underwood, Elizabeth; Varnes, Jeffrey G.; Xue, Lin; Yao, Tieguang; Zhang, Ke; Zhang, Andrew X.; Zheng, Xiaolan published their research in Journal of Medicinal Chemistry in 2021. The article was titled 《Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-N-methylpyridine-2-carboxamide (AZD5305): A PARP1-DNA Trapper with High Selectivity for PARP1 over PARP2 and Other PARPs》.HPLC of Formula: 329-59-9 The article contains the following contents:
Poly-ADP-ribose-polymerase (PARP) inhibitors have achieved regulatory approval in oncol. for homologous recombination repair deficient tumors including BRCA mutation. However, some have failed in combination with first-line chemotherapies, usually due to overlapping hematol. toxicities. Currently approved PARP inhibitors lack selectivity for PARP1 over PARP2 and some other 16 PARP family members, and we hypothesized that this could contribute to toxicity. Recent literature has demonstrated that PARP1 inhibition and PARP1-DNA trapping are key for driving efficacy in a BRCA mutant background. Herein, we describe the structure- and property-based design of AZD5305, I, a potent and selective PARP1 inhibitor and PARP1-DNA trapper with excellent in vivo efficacy in a BRCA mutant HBCx-17 PDX model. Compound 25 is highly selective for PARP1 over other PARP family members, with good secondary pharmacol. and physicochem. properties and excellent pharmacokinetics in preclin. species, with reduced effects on human bone marrow progenitor cells in vitro. The experimental part of the paper was very detailed, including the reaction process of Methyl 4-fluoro-3-nitrobenzoate(cas: 329-59-9HPLC of Formula: 329-59-9)
Methyl 4-fluoro-3-nitrobenzoate(cas: 329-59-9) belongs to methyl benzoate. Methyl benzoate reacts at both the ring and the ester, depending on the substrate. Electrophiles attack the ring, illustrated by acid-catalysed nitration with nitric acid to give methyl 3-nitrobenzoate.HPLC of Formula: 329-59-9Methyl 4-fluoro-3-nitrobenzoate is used to prepare dimethyl 3-nitro-3′,4-oxydibenzoate by reacting with 3-hydroxy-benzoic acid methyl ester.
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