34529-06-1Relevant academic research and scientific papers
Designed, synthesized and biological evaluation of proteolysis targeting chimeras (PROTACs) as AR degraders for prostate cancer treatment
Ke, Yu,Liang, Jian-Jia,Liu, Hong-Min,Shan, Li-Hong,Wang, Ni,Wang, Ya-Lei,Wang, Zhi-Jia,Xie, Hang,Yang, Rui-Hua,Zheng, Zi-Jun,Zhou, Chen
, (2021/08/09)
As a continuation of our research on developing potent and potentially safe androgen receptor (AR) degrader, a series of novel proteolysis targeting chimeras (PROTACs) containing the phthalimide degrons with different linker were designed, synthesized and evaluated for their AR degradation activity against LNCaP (AR+) cell line. Most of the synthesized compounds displayed moderate to satisfactory AR binding affinity and might lead to antagonist activity against AR. Among them, compound A16 exhibited the best AR binding affinity (85%) and degradation activity against AR. Due to the strong fluorescence properties of pomalidomide derivatives, B10 was found to be effectively internalized and visualized in LNCaP (AR + ) cells than PC-3 (AR-) cells. Moreover, the molecular docking of A16 with AR and the active site of DDB1-CRBN E3 ubiquitin ligase complex provides guidance to design new PROTAC degrons targeting AR for prostate cancer therapy. These results represent a step toward the development of novel and improved AR PROTACs.
Fluorescent probe targeting androgen receptor, and preparation method thereof
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Paragraph 0049; 0050, (2020/02/20)
The invention discloses a fluorescent probe targeting an androgen receptor, and a preparation method thereof, particularly relates to an AR fluorescent probe obtained by linking a pomalidomide fluorophore to an androgen receptor (AR) non-steroidal antagonist skeleton, and belongs to the field of medicinal chemistry. According to the invention, the fluorescent probe has a structural general formuladefined in the specification, and can selectively image androgen receptor high-expression cells at the cellular level, and the synthesis process is simple and feasible, cheap and easily available inraw materials, low in preparation cost and easy to popularize.
Method for preparing dimethyl aminophthalate
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Paragraph 0021-0026, (2020/08/22)
The invention relates to a method for preparing dimethyl aminophthalate. The method comprises the following steps: dissolving nitrophthalic anhydride in methanol, adding a graphite-phase carbon nitride supported cuprous catalyst (g-C3N4/Cu2O) and a catalytic amount of acetic anhydride, and carrying out reacting to obtain dimethyl aminophthalate, wherein 200-300 mg of the graphite-phase carbon nitride supported cuprous catalyst (g-C3N4/Cu2O) is used for every millimole of nitrophthalic anhydride, and 0.05-0.08 mmol of acetic anhydride is used for every millimole of nitrophthalic anhydride.
A green synthetic process for dimethyl 3-amino o-phthalate
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Paragraph 0021; 0023; 0024; 0026, (2019/07/16)
The invention relates to a green synthetic process for dimethyl 3-amino o-phthalate. The process includes (1) reacting 3-nitro phthalic anhydride and methanol at room temperature under the function ofa solid acid catalyst to obtain dimethyl 3-nitro o-phthalate; and (2) dissolving the obtained dimethyl 3-nitro o-phthalate into an organic solvent, and reacting under the function of a reductant to obtain the dimethyl 3-amino o-phthalate.
AZA-PHENALENE-3-KETONE DERIVATIVE, PREPARATION METHOD THEREOF, AND ITS APPLICATION AS PARP INHIBITOR
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Paragraph 0021, (2018/05/26)
Disclosed are an aza-phenalene-3-ketone derivative, a preparation method thereof and its application as a PARP inhibitor. The aza-phenalene-3-ketone derivative has the following structure: wherein R is hydrogen, methyl, ethyl, isopropyl, benzyl or 3-methyl-3-butenyl. The aza-phenalene-3-ketone derivative has very high activity for inhibiting PARP, thereby providing a good basis for new drug research of developing a nitrogen-doped phenalene-3-ketone compound as PARP inhibitor to treat cancer.
Preparation of 2-phenyl-3-hydroxyquinoline-4(1H)-one-5-carboxamides as potential anticancer and fluorescence agents
Funk, Petr,Motyka, Kamil,D?ubák, Petr,Znojek, Pawel,Gurská, Soňa,Kusz, Joachim,McMaster, Claire,Hajdúch, Marián,Soural, Miroslav
, p. 48861 - 48867 (2015/06/16)
The synthesis of 3-hydroxyquinoline-4(1H)-one derivatives bearing substituted phenyl in position 2 and variously substituted carboxamide group in position 5 is described, with use of 3-nitrophthalic anhydride, α-haloketones and primary amines as the starting materials. The synthetic approach was inspired by the preparation of analogous derivatives reported previously. However, a different strategy had to be developed with the corresponding bis(phenacyl)-3-aminophthalates as the key intermediates. Synthesized hydroxyquinolinones, as well as their intermediates, were tested for their cytotoxic activity towards various cancer and non-malignant cell lines. The fluorescent properties of these compounds have also been evaluated. In both fields, interesting data were obtained and compared to isomeric compounds that have been studied in the past.
FUSED TETRA OR PENTA-CYCLIC PYRIDOPHTHALAZINONES AS PARP INHIBITORS
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Page/Page column 48; 49, (2013/07/19)
Provided are certain fused tetra or penta-cyclic compounds and salts thereof, compositions thereof, and methods of use thereof.
PARP INHIBITOR COMPOUNDS, COMPOSITIONS AND METHODS OF USE
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Page/Page column 22, (2009/04/24)
The present invention relates to tetraaza phenalen-3-one compounds which inhibit poly (ADP-ribose) polymerase (PARP) and are useful in the chemosensitization of cancer therapeutics. The induction of peripheral neuropathy is a common side-effect of many of the conventional and newer chemotherapies. The present invention further provides means to reliably prevent or cure chemotherapy-induced neuropathy. The invention also relates to the use of the disclosed PARP inhibitor compounds in enhancing the efficacy of chemotherapeutic agents such as temozolomide. The invention also relates to the use of the disclosed PARP inhibitor compounds to radiosensitize tumor cells to ionizing radiation. The invention also relates to the use of the disclosed PARP inhibitor compounds for treatment of cancers with DNA repair defects.
4'-O-SUBSTITUTED ISOINDOLINE DERIVATIVES AND COMPOSITIONS COMPOSITIONS COMPRISING AND METHODS OF USING THE SAME
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, (2008/12/07)
Provided are 4'-O substituted isoindoline compounds, and pharmaceutically acceptable salts, solvates, clathrates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.
Discovery of indenopyrazoles as EGFR and VEGFR-2 tyrosine kinase inhibitors by in silico high-throughput screening
Usui, Taikou,Ban, Hyun Seung,Kawada, Junpei,Hirokawa, Takatsugu,Nakamura, Hiroyuki
, p. 285 - 288 (2008/09/17)
A series of indenopyrazoles 8 and 9 were designed and synthesized as EGFR tyrosine kinase inhibitors by in silico high-throughput screening. Compounds 8b and 8d showed significant inhibition of A431 cell growth (GI50 = 0.062 and 0.057 μM, respectively). Compounds 8b and 9a showed inhibitory activity toward both EGFR and VEGFR-2 (KDR) tyrosine kinases, whereas 8d inhibited VEGFR-2 tyrosine kinase, exclusively.
