78256-05-0Relevant articles and documents
Novel phenanthridin-6(5H)-one derivatives as potent and selective BET bromodomain inhibitors: Rational design, synthesis and biological evaluation
Zhi, Yanle,Wang, Shu,Huang, Wenhai,Zeng, Shenxin,Liang, Meihao,Zhang, Chixiao,Ma, Zhen,Wang, Zunyuan,Zhang, Zhimin,Shen, Zhengrong
, p. 502 - 514 (2019)
Inhibition of BET family of bromodomain is an appealing intervention strategy for several cancers and inflammatory diseases. This article highlights our work toward the identification of potent, selective, and efficacious BET inhibitors using a structure-
In Vitro and Cellular Probes to Study PARP Enzyme Target Engagement
Blackwell, Danielle J.,Church, W. David,Desai, Hetvi J.,Keilhack, Heike,Kuntz, Kevin W.,Lu, Alvin Z.,Majer, Christina R.,Niepel, Mario,Perl, Nicholas R.,Ren, Yue,Santospago, Andrew G.,Schenkel, Laurie B.,Swinger, Kerren K.,Vasbinder, Melissa M.,Wigle, Tim J.
, p. 877 - 887 (2020/07/16)
Poly(ADP-ribose) polymerase (PARP) enzymes use nicotinamide adenine dinucleotide (NAD+) to modify up to seven different amino acids with a single mono(ADP-ribose) unit (MARylation deposited by PARP monoenzymes) or branched poly(ADP-ribose) polymers (PARylation deposited by PARP polyenzymes). To enable the development of tool compounds for PARP monoenzymes and polyenzymes, we have developed active site probes for use in in vitro and cellular biophysical assays to characterize active site-directed inhibitors that compete for NAD+ binding. These assays are agnostic of the protein substrate for each PARP, overcoming a general lack of knowledge around the substrates for these enzymes. The in vitro assays use less enzyme than previously described activity assays, enabling discrimination of inhibitor potencies in the single-digit nanomolar range, and the cell-based assays can differentiate compounds with sub-nanomolar potencies and measure inhibitor residence time in live cells. Wigle et al. describe a versatile set of NAD+-competitive probes for PARP enzymes that are used to build high-throughput in vitro and cellular biophysical assays that enable inhibitor screening and determination of residence time.
Phenanthridinone compound with BRD4 protein inhibiting effect and preparation method and application thereof
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, (2019/10/04)
The invention discloses a phenanthridinone compound with BRD4 protein inhibiting effect, a preparation method and application thereof. The phenanthridinone compound comprises a compound with a structure shown in a formula (I) and pharmaceutically acceptab
Metal-Oxidant-Free Cobalt-Catalyzed C(sp2)-H Carbonylation of ortho-Arylanilines: An Approach toward Free (NH)-Phenanthridinones
Ling, Fei,Zhang, Chaowei,Ai, Chongren,Lv, Yaping,Zhong, Weihui
, p. 5698 - 5706 (2018/05/23)
A traceless directing group assisted Co-catalyzed C(sp2)-H carbonylation of ortho-arylanilines for the synthesis of free (NH)-phenanthridinones in metal-based-oxidant-free fashion was accomplished. This protocol employs diisopropyl azodicarboxylate as the CO source and oxygen as the sole oxidant, and provides good yields with various functional tolerance. The methodology has been applied for the total synthesis of PARP inhibitor PJ-34. Furthermore, the kinetic isotopic effect experiments reveal the C-H bond cleavage probably occurred in the rate-determining step.
Environment-friendly synthetic method of 6(5H)-phenanthridine derivative
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Paragraph 0021; 0022, (2018/11/22)
The invention discloses an environment-friendly synthetic method of a 6(5H)-phenanthridine derivative. The method specifically comprises the step of carrying out catalyzed oxidation by virtue of metalcobalt, so as to realize the high-selectivity and high-yield preparation of the 6(5H)-phenanthridine derivative, wherein N-([1,1'-biphenyl]-2-yl)pyridine amide is take as the raw material, azodiformate is taken as a carbonyl source for replacing poisonous and harmful carbon monoxide, and oxygen is taken as an oxidant. The environment-friendly synthetic method has the characteristics that the rawmaterial is easily available, the operation is simple and convenient, the chemical selectivity and the regional selectivity are high, and the like; and the environment-friendly synthetic method has relatively high implement values and social and economic values.
Synthesis and biological evaluation of biphenyl amides that modulate the US28 receptor
Kralj, Ana,Kurt, Elif,Tschammer, Nuska,Heinrich, Markus R.
, p. 151 - 168 (2014/01/17)
To prepare and biologically evaluate 38 new potential US28 allosteric modulators, we employed a straightforward synthetic route involving radical arylation. The study was based on a former lead structure but with the dihydroisoquinolinone moiety replaced by substituted biphenyls. The investigation of structure-activity relationships among the new biphenyl-derived ligands led to a preliminary pharmacophore model and the discovery of four promising candidates with full inverse agonist properties. Hit HCMV GPCRs ASAP! Employing a straightforward synthetic access involving radical arylation, 38 new potential US28 allosteric modulators were prepared and biologically evaluated. The investigation of structure-activity relationships among the new biphenyl-derived ligands led to a consistent model and the discovery of four promising candidates with full inverse agonist properties. Copyright
Pd(II)-catalyzed C(sp2)-H carbonylation of biaryl-2-amine: Synthesis of phenanthridinones
Liang, Zunjun,Zhang, Jitan,Liu, Zhanxiang,Wang, Kai,Zhang, Yuhong
, p. 6519 - 6526 (2013/07/26)
A Pd(OAc)2-catalyzed C(sp2)-H carbonylation protocol of arenes under carbon monoxide atmosphere has been developed. The scope of the carbonylation reaction is broad and tolerates a variety of useful functional groups. This reaction provides a novel and efficient method for the synthesis of biologically and pharmaceutically significant phenanthridinones.
Methods for the treatment of neurodegenerative disorders using substituted phenanthridinone derivatives
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, (2008/06/13)
This invention provides a novel class of substituted 6(5H)phenanthridinone compounds. The invention also includes pharmaceutical compositions, and methods of making and using the compounds, or a pharmaceutically acceptable salt, hydrate, prodrug, or mixture thereof. Methods of using the compounds and pharmaceutical compositions for treating neurodegenerative disorders, such as multiple sclerosis are also described.
Substituted phenanthridinones and methods of use thereof
-
, (2008/06/13)
This invention provides a novel class of substituted 6(5H)phenanthridinone compounds. Pharmaceutical compositions, and methods of making and using the compounds, or a pharmaceutically acceptable salt, hydrate, prodrug, or mixture thereof are also described.
Synthesis of substituted 5[H]phenanthridin-6-ones as potent poly(ADP-ribose)polymerase-1 (PARP1) inhibitors
Li, Jia-He,Serdyuk, Larisa,Ferraris, Dana V.,Xiao, Ge,Tays, Kevin L.,Kletzly, Paul W.,Li, Weixing,Lautar, Susan,Zhang, Jie,Kalish, Vincent J.
, p. 1687 - 1690 (2007/10/03)
1-, 2-, 3-, 4-, 8-, or 10-Substituted 5(H)phenanthridin-6-ones were synthesized and found to be potent PARP1 inhibitors. Among the 28 compounds prepared, some showed not only low IC50 values (compound 1b, 10 nM) but also desirable water solubility characteristics. These properties, which are superior to the common PARP1 inhibitors such as benzamides and isoquinolin-1-ones, are essential for potential therapeutic usage. The variety of compounds allows SAR analysis of favored substituents and substituted positions on 5(H)phenanthridin-6-one ring.
