- COMPOUND INHIBITING YAP-TEAD BINDING, AND PHARMACEUTICAL COMPOSITION FOR PREVENTING OR TREATING CANCER, COMPRISING COMPOUND AS ACTIVE INGREDIENT
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The present invention relates to a compound which inhibits the binding of Yes associated protein (YAP) and transcriptional enhancer associate domain (TEAD), a prodrug of same, a hydrate of same, a solvate of same or a pharmaceutically acceptable salt of same, and a composition comprising same as an active ingredient, the compound according to the present invention being able to be applied as an inhibitor which can directly inhibit YAP-TEAD binding in the Hippo pathway which plays a crucial role in the occurrence of cancer.
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Paragraph 0138-0139
(2021/09/24)
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- TRICYCLIC DEGRADERS OF IKAROS AND AIOLOS
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Tricyclic cereblon binders for the degradation of Ikaros or Aiolos by the ubiquitin proteasome pathway for therapeutic applications are described.
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Page/Page column 248-249
(2020/10/21)
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- Cobalt-Catalyzed Direct Carbonylative Synthesis of Free (NH)-Benzo[ cd]indol-2(1 H)-ones from Naphthylamides
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A cobalt-catalyzed C-H carbonylation of naphthylamides for the synthesis of benzo[cd]indol-2(1H)-one scaffolds has been developed. The reaction employs a traceless directing group and uses benzene-1,3,5-triyl triormate as the CO source, affording various free (NH)-benzo[cd]indol-2(1H)-ones in moderate to high yields (up to 88%). Using this protocol, the total synthesis of BET bromodomain inhibitors A and B was accomplished as well.
- Ying, Jun,Fu, Lu-Yang,Zhong, Guoqiang,Wu, Xiao-Feng
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p. 5694 - 5698
(2019/07/08)
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- Preparation method of 1,8-disubstituted naphthalene series polycyclic aromatic hydrocarbon mononitration derivative
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The invention provides a preparation method of 1,8-disubstituted naphthalene series polycyclic aromatic hydrocarbon mononitration derivative. The preparation method is characterized by comprising thefollowing steps: S1, dissolving 1,8-disubstituted naphthalene series polycyclic aromatic hydrocarbon and subgroup metal nitrate in an organic solvent, performing a nitration reaction under 10-60 DEG Cfor 4-10 h, and then monitoring by TLC (Thin layer chromatography) till a raw material point disappears to finish the reaction; S2, cooling a product obtained in S1 to room temperature, performing suction filtration, washing filter cake with 5-10 mL of H2O and anhydrous C2H5OH separately, and performing vacuum drying to obtain the 1,8-disubstituted naphthalene series polycyclic aromatic hydrocarbon mononitration derivative. According to the preparation method of the 1,8-disubstituted naphthalene series polycyclic aromatic hydrocarbon mononitration derivative, the product yield is 93%-96%; theproduct purity is 98%-99.5%; compared with the prior art, the preparation method has the characteristics of high product yield, high purity, low cost and simple process, and is easy to industrialize.
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Paragraph 0070-0072
(2019/08/06)
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- Preparation method of 1,8-disubstituted naphthalene mononitration derivative
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The invention provides a preparation method of 1,8-disubstituted naphthalene mononitration derivative. The preparation method is characterized by comprising the following steps: S1, taking 1,8-disubstituted naphthalene as a raw material, taking main group metal nitrate as a nitration reagent, dissolving the 1,8-disubstituted naphthalene and the main group metal nitrate in an organic solvent, performing a nitration reaction under 10-60 DEG C for 4-10 h, and then monitoring by TLC (Thin layer chromatography) till a raw material point disappears to finish the reaction; S2, cooling a product obtained in step S1 to room temperature, performing suction filtration, washing filter cake with 5-10 mL of H2O and anhydrous C2H5OH separately, and performing vacuum drying to obtain the 1,8-disubstitutednaphthalene mononitration derivative. According to the preparation method of the 1,8-disubstituted naphthalene mononitration derivative, the product yield can reach 90%-95%; the product purity reaches 98.5%-99.6%; compared with the prior art, the preparation method has the characteristics of high product yield, high purity, low cost and simple process, and is easy to industrialize.
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Paragraph 0071-0073
(2019/08/06)
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- Discovery of Benzo[ cd]indol-2(1 H)-ones and Pyrrolo[4,3,2- de]quinolin-2(1 H)-ones as Bromodomain and Extra-Terminal Domain (BET) Inhibitors with Selectivity for the First Bromodomain with Potential High Efficiency against Acute Gouty Arthritis
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The bromodomain and extra-terminal domain (BET) family of proteins are readers which specifically recognize histone-acetylated lysine residues. Each BET bromodomain protein contains two highly homologous domains: the first bromodomain (BD1) and the second bromodomain (BD2). Pan-BET bromodomain inhibition is a potential therapy for various cancers and immune-inflammatory diseases, but only few reported inhibitors show selectivity within the BET family. Herein, we identified a series of benzo[cd]indol-2(1H)-ones and pyrrolo[4,3,2-de]quinolin-2(1H)-ones with good selectivity for BET BD1. Through structure-based optimization, highly active and selective compounds are ultimately obtained. The representative compounds are the first reported inhibitors with selectivity more than 100-fold for BRD4(1) over BRD4(2). Among them, we further show that 68 (LT052) mediates BRD4/NF-κB/NLRP3 signaling inflammatory pathways with comparable protein expression and significantly improves symptoms of gout arthritis in a rat model. Therefore, selective pharmacological modulation of individual bromodomains could represent a strategy for the treatment of acute gouty arthritis.
- Jiang, Fei,Hu, Qinghua,Zhang, Zhimin,Li, Hongmei,Li, Huili,Zhang, Dewei,Li, Hanwen,Ma, Yu,Xu, Jingjing,Chen, Haifang,Cui, Yong,Zhi, Yanle,Zhang, Yanmin,Xu, Junyu,Zhu, Jiapeng,Lu, Tao,Chen, Yadong
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p. 11080 - 11107
(2019/12/24)
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- Naphthalene imide-polyamine conjugate, preparation method and application thereof
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The application provides a naphthalene imide-polyamine conjugate, a preparation method thereof and applications and belongs to the technical field of medicinal chemistry. The naphthalene imide-polyamine conjugate has the structure as shown in the specific
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Paragraph 0045; 0049
(2019/05/02)
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- Identification of benzo[cd]indol-2(1H)-ones as novel Atg4B inhibitors via a structure-based virtual screening and a novel AlphaScreen assay
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Targeting autophagy is a promising therapeutic strategy for cancer treatment. As a result, the identification of novel autophagy inhibitors is an emerging field of research. Herein, we report the development of a novel AlphaScreen HTS assay that combined
- Quintana, Mireia,Bilbao, Ana,Comas-Barceló, Júlia,Bujons, Jordi,Triola, Gemma
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p. 648 - 666
(2019/06/21)
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- Design, synthesis and biological evaluation of naphthostyril derivatives as novel protein kinase FGFR1 inhibitors
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New class of FGFR1 kinase inhibitors with naphthostyril heterocycle has been identified. A series of N-phenylnaphthostyril-1-sulfonamides has been synthesized and tested in vitro. It was revealed that the most active compound N-(4-hydroxyphenyl)naphthostyril-1- sulfonamide inhibited FGFR1 with IC50 of 2 μM. In our preliminary studies, N-phenylnaphthos-tyril- 1-sulfonamides demonstrated selectivity of FGFR1 inhibition and antiproliferative activity on cancer cell line. N-phenylnaphthostyril-1-sulfonamides have a good potential for further development as anticancer agents.
- Gryshchenko, Andrii Anatoliyovych,Levchenko, Kostiantyn Vasyliovych,Bdzhola, Volodymyr Grygorovich,Ruban, Tatiana Panasivna,Lukash, Lyubov Leonidovna,Yarmoluk, Sergiy Mikolayovych
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p. 126 - 132
(2015/03/03)
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- Antiproliferative compounds having nitrogen-containing tricyclic ring systems and phenyl substituents
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The invention relates to TS-inhibiting compounds of the formula STR1 where W is an alkylene group; D is a structure having two rings that are unsubstituted or substituted, where (i) one ring is a phenyl ring and (ii) the other ring is a phenyl ring or a 6
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- Crystal-Structure-Based Design and Synthesis of Benzindole-Containing Inhibitors of Thymidylate Synthase
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The X-ray crystal-structure-based design, synthesis, and biological activity of a novel family of benzindole-containing inhibitors of thymidylate synthase (TS) are described.The structure-activity of the lead compound was studied by conceptually dividing the molecule into four regions and independently optimizing the substituents for each region.Combination of favored substituents for each region led to inhibitors with Ki's against the human enzyme in the range of 10-20 nM.Thymidine shift experiments suggested that the cytotoxic properties of the best enzyme inhibitors were due to TS targeting in cells.The inhibitors were synthesized from substituted 6-aminobenzindol-2(1H)-ones by alkylation with both a simple alkyl group and a substituted benzylic portion.The 2,6-diaminobenzindoles were prepared from the corresponding lactams by conversion to the thiolactam, alkylation to the methylated thiolactam, and then displacement with a substituted or unsubstituted amine.
- Varney, Michael D.,Marzoni, Gifford P.,Palmer, Cindy L.,Deal, Judith G.,Webber, Stephanie,et al.
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p. 663 - 676
(2007/10/02)
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