13365-26-9Relevant 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)
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.
A Spiroalkylation Method for the Stereoselective Construction of α-Quaternary Carbons and Its Application to the Total Synthesis of (R)-Puraquinonic Acid
Elmehriki, Adam A. H.,Gleason, James L.
, p. 9729 - 9733 (2019)
Cyclic α-quaternary carbon stereocenters were prepared from biselectrophillic substrates and an easily prepared chiral bicyclic sulfonyl lactam. This was achieved in two steps by spiroalkylation, employing biphasic reaction conditions with a phase-transfer catalyst, followed by reduction and alkylation with a series of alkyl halide electrophiles. The products of this method were isolated in good yields with with high levels of diastereoselectivity. This methodology was employed in the enantioselective total synthesis of (R)-puraquinonic acid (1) for a late-stage installation of the α-quaternary carbon stereocenter. This enabled the shortest synthesis of 1 to date, an eight-pot sequence providing an overall yield of 14%.
Fluorescent probe targeting androgen receptor, and preparation method thereof
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Paragraph 0047; 0048, (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.
A green synthetic process for dimethyl 3-amino o-phthalate
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Paragraph 0021; 0022; 0024; 0025, (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.
A 2 - ethoxy benzimidazole - 7 - carboxylic acid methyl ester
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Paragraph 0033; 0040-0043, (2018/05/24)
The invention discloses a synthesis method of 2-ethoxy benzimidazole-7-carboxylic acid methyl ester. The problem that an existing process is not high in content and is very low in yield is solved. According to the synthesis method, 3-nitryl phthalic acid is used as a raw material, rearrangement is performed in a water solution after methyl esterification, acylation and re-nitridation, then tin powder is adopted to perform reduction and loop closing so as to obtain the 2-ethoxy benzimidazole-7-carboxylic acid methyl ester. By the adoption of the synthesis method, produced impurities are very little, the content is high, and the yield is also high.
AZA-PHENALENE-3-KETONE DERIVATIVE, PREPARATION METHOD THEREOF, AND ITS APPLICATION AS PARP INHIBITOR
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Paragraph 0020, (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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Page/Page column 48-49, (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.
