- SKLB1039 Compound as well as preparation method and application thereof
-
The invention belongs to the technical field of preparation of new compounds, and particularly relates SKLB1039 compound as well as a preparation method and application thereof. The 2 -methyl -3 -nitrobenzoic acid is taken as an initial raw material and is brominated. Esterification, reduction, reductive amination and hydrolysis synthesis 5 - bromo -2 - methyl -3 - (N - ethyl, N - (tetrahydropyran -4 - yl)) aminobenzoic acid. The cyclohexanone serving as a raw material is subjected to catalytic hydrogenation reduction of carbonyl α, acetyl cyclohexanone and cyanopyridone to synthesize 4 - aminomethyl -1 - methyl -5, 6, 7, 8 - tetrahydroisoquinoline -3 (2H) - ketone. Coupling the two to an amide is followed by catalytic coupling with an aryl sheet to give SKLB1039 a compound. SKLB1039 Large-scale preparation technology is provided, operation is easy, the post-treatment purification process is simple, the total route yield is improved, raw materials are easy to purchase, the price is low, and the production cost is greatly reduced.
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Paragraph 0030; 0039-0043
(2021/10/27)
-
- Synthesis and evaluation of a novel series of 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylic acid-substituted amide derivatives as anticancer, antiangiogenic, and antioxidant agents
-
A series of novel indazole derivatives has been synthesized and evaluated for anticancer, antiangiogenic, and antioxidant activities. The capability of the synthesized compounds 11a–x to hinder the viability of three human cancer cells lines, HEP3BPN 11 (liver), MDA 453 (breast), and HL 60 (leukemia), were assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Among the compounds 11a–x screened, 11c and 11d showed the higher inhibitory activity on the viability of HEP3BPN 11 (liver), when compared with the standard methotrexate. These compounds were further tested to evaluate their potential to inhibit the proangiogenic cytokines associated with tumor development. Compound 11c was found to be a potent antiangiogenic agent against TNFα, VEGF, and EGF, whereas 11d showed potent antiangiogenic activity against TNFα, VEGF, IGF1, TGFb, and leptin inhibition. All the compounds 11a–x were screened for their antioxidant activities using 2,2-diphenyl-1-picryl hydrazine (DPPH), hydroxyl (OH), and superoxide radical (SOR) scavenging activity. Compounds 11n, 11p, 11q, and 11v have shown significant OH radical scavenging activities, also compounds 11c, 11h, and 11k were found to have a DPPH radical scavenging activity and compounds 11a and 11m exhibited better SOR scavenging activity when compared with the reference compound ascorbic acid. In silico molecular docking analysis revealed important structural insights behind observed anti TNFα effect by present indazole compounds.
- Sawant, Ajay S.,Kamble, Sonali S.,Pisal, Parshuram M.,Meshram, Rohan J.,Sawant, Sanjay S.,Kamble, Vilas A.,Kamble, Vinod T.,Gacche, Rajesh N.
-
-
- Design and synthesis of (E)-1,2-diphenylethene-based EZH2 inhibitors
-
Enhancer of zeste homolog 2 (EZH2) serves as the catalytic subunit of the polycomb repression complex 2 (PRC2), which is implicated in cancer progression metastasis and poor prognosis. Based on our EZH2 inhibitor SKLB1049 with low nanomolar activity, we e
- Feng, Qiang,Feng, Zhanzhan,He, Hualong,Hu, Xi,Liu, Zhihao,Teng, Fei,Yu, Luoting,Zhang, Qiangsheng
-
supporting information
(2020/01/22)
-
- EZH2 inhibitor as well as preparation of EZH2 inhibitor and application of EZH2 inhibitor in anti-tumor treatment
-
The invention discloses an EZH2 inhibitor as well as preparation of the EZH2 inhibitor and application of the EZH2 inhibitor in anti-tumor treatment. The EZH2 inhibitor has a structure represented bya general formula I shown in the description, wherein de
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Paragraph 0111-0113
(2019/08/20)
-
- SELECTIVE INHIBITORS OF CLINICALLY IMPORTANT MUTANTS OF THE EGFR TYROSINE KINASE
-
The present invention provides compounds of Formula (I) or a subgeneric structure or species thereof, or a pharmaceutically acceptable salt, ester, solvate, and/or prodrug thereof, and methods and compositions for treating or ameliorating abnormal cell pr
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Page/Page column 145; 146
(2019/01/21)
-
- HISTONE METHYLTRANSFERASE EZH2 INHIBITOR, PREPARATION METHOD AND PHARMACEUTICAL USE THEREOF
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The invention relates to a histone methyltransferase EZH2 inhibitor, a preparation method and pharmaceutical use thereof. In particular, the invention relates to a compound represented by the general formula (I), a preparation method thereof, a pharmaceut
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-
Paragraph 0291
(2019/11/22)
-
- QUINAZOLINONE DERIVATIVE, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION, AND APPLICATIONS
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Disclosed are a quinazolinone derivative, a preparation method therefor, a pharmaceutical composition, and applications. Provided are a compound represented by formula I, a pharmaceutically acceptable salt, a solvate, a crystal form, a eutectic crystal, a
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-
Paragraph 0108; 0109
(2018/12/04)
-
- COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ENHANCER OF ZESTE HOMOLOG 2 POLYPEPTIDE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
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-
Paragraph 1230-1234
(2018/07/15)
-
- MDM2-BASED MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
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The description relates to MDM2 binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the MDM2 E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.
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-
Paragraph 0422-0423
(2017/01/31)
-
- Pyridone derivatives and its preparation and use
-
The invention belongs to the field of chemical medicines, and particularly relates to a pyridone derivative, a preparation method and an application thereof. The pyridone derivative is represented as the formula (I). The invention also provides the prepar
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Paragraph 0199; 0200; 0201
(2016/10/20)
-
- Dihydrothiazolone compounds containing sulfamide and pharmaceutical compositions and use thereof
-
The invention provides dihydrothiazolone compounds containing sulfamide, represented by a formula (I), pharmaceutical compositions and use thereof. The compounds can be combined with proteins with bromodomain structural domains so as to adjust a downstream signal channel and exert a special function, and can be used for treating many diseases associated with bromodomain structural domains. The compounds can interfere combination of Brd4 with the bromodomain structural domain and an acetylized histone so as to down-regulate transcription of a cancer gene c-myc and associated target genes thereof, so that the compounds can become effective therapeutic drugs for treating tumors.
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-
Paragraph 0198; 0199; 0200; 0203
(2016/10/08)
-
- HYDROCHLORIDE SALT FORM FOR EZH2 INHIBITION
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Provided herein are novel solid forms of N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5 -(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide hydrochloride, and related compositions and methods.
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-
Paragraph 085
(2015/05/05)
-
- SUBSTITUTED BENZENE AND 6,5-FUSED BICYCLIC HETEROARYL COMPOUNDS
-
The present invention relates to substituted benzene compounds and bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.
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-
Paragraph 0655-0657
(2016/05/02)
-
- NOVEL COMPOUNDS
-
The present invention relates to novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.
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Page/Page column 23
(2015/12/18)
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- NOVEL COMPOUNDS
-
Disclosed are novel retinoid-related orphan receptor gamma (RORγ) modulators and their use in the treatment of diseases mediated by RORγ.
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Page/Page column 80; 81
(2015/12/17)
-
- Substituted Benzene Compounds
-
The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.
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-
Paragraph 0157; 0158
(2014/05/07)
-
- PROCESSES FOR PREPARING ISOINDOLINE-1,3-DIONE COMPOUNDS
-
Provided herein are processes for preparing an isoindoline- 1.3-dione compound, or an enantiomer or a mixture of enantiomers thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or polymorph thereof.
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-
Paragraph 00181; 00182
(2014/02/16)
-
- METHOD OF TREATMENT
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The present invention relates to a method of treating T cell mediated inflammatory immune diseases or T cell mediated hypersensitivity diseases, which comprises administering to a human in need thereof an effective amount of a compound which inhibits EZH2 and/or EZH1, or a pharmaceutically acceptable salt thereof.
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Paragraph 0826
(2014/09/29)
-
- 1,4-PYRIDONE BICYCLIC HETEROARYL COMPOUNDS
-
The present invention relates to 1,4-pyridone bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical co
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-
Paragraph 0551
(2014/07/08)
-
- SALT FORM OF A HUMAN HI STONE METHYLTRANSF ERASE EZH2 INHIBITOR
-
Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4'-(morpholinomethyl)-[1,1'-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compo
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Page/Page column 44
(2013/11/05)
-
- COMBINATION THERAPY FOR TREATING CANCER
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The present invention relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, particularly anticancer agents such as prednisone, and methods of combination therapy for administering t
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-
Paragraph 0323; 0324
(2013/11/05)
-
- Aryl- or Heteroaryl-Substituted Benzene Compounds
-
The present invention relates to aryl- or heteroaryl-substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.
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Page/Page column 100
(2012/10/23)
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- SUBSTITUTED BENZENE COMPOUNDS
-
The present invention relates to substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.
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Page/Page column 288
(2012/11/06)
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- SUBSTITUTED 6,5-FUSED BICYCLIC HETEROARYL COMPOUNDS
-
The present invention relates to substituted 6,5 -fused bicyclic heteroaryl compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof.
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Page/Page column 311
(2012/09/21)
-
- The discovery and structure-activity relationships of pyrano[3,4-b]indole- based inhibitors of hepatitis C virus NS5B polymerase
-
We describe the structure-activity relationship of the C7-position of pyrano[3,4-b]indole-based inhibitors of HCV NS5B polymerase. Further exploration of the allosteric binding site led to the discovery of the significantly more potent compounds 13 and 14
- Jackson, Randy W.,Laporte, Matthew G.,Herbertz, Torsten,Draper, Tandy L.,Gaboury, Janet A.,Rippin, Susan R.,Patel, Ravi,Chunduru, Srinivas K.,Benetatos, Christopher A.,Young, Dorothy C.,Burns, Christopher J.,Condon, Stephen M.
-
scheme or table
p. 3227 - 3231
(2011/07/07)
-
- INDAZOLES
-
Herein are disclosed indazoles of formula (I) where the various groups are defined herein, and which are useful for treating cancer.
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Page/Page column 94
(2011/11/30)
-
- ALPHA-CARBOLINE DERIVATIVES AND METHODS FOR PREPARATION THEREOF
-
To provide methods for preparing alpha-carboline derivatives in few steps, as well as conveniently and industrially advantageously. A method for preparation of a compound represented by Formula (II) or a salt thereof, comprising subjecting a compound represented by Formula (I) or a salt thereof to a ring closure reaction in the presence of a palladium catalyst, a ligand, and a base; a method for preparation of a compound represented by Formula (IX) or a salt thereof, comprising subjecting a compound represented by Formula (VII) or a salt thereof to a ring closure reaction in the presence of a palladium catalyst, a ligand, and a base, and subsequently to an aromatization reaction; and methods for preparation of compounds represented by Formulae (XV), (XVII), and (XIX) or a salt thereof, comprising subjecting respective compounds represented by Formulae (II) and (IX) or a salt thereof to a reaction for introducing a leaving group when necessary, and subsequently to a coupling reaction: wherein the symbols respectively represent the same meaning as defined in the present specification.
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Page/Page column 183-184
(2008/06/13)
-
- Pyranouidole Derivatives and the Use Thereof for the Treatment of Hepatitis C Virus Infection or Disease
-
The invention is directed to novel pyranoindole derivatives and analogs as well as compositions containing the same and to the use thereof for the treatment, prevention or inhibition of viral infections and associated diseases caused by the Hepatitis C vi
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Page/Page column 23
(2010/11/28)
-
- CHEMICAL COMPOUNDS
-
The invention is directed to novel indazole carboxamide derivatives. Specifically, the invention is directed to compounds according to formula (I) where R1 and R2 are as defined below. These compounds are useful in the treatment of disorders associated wi
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Page/Page column 19; 36
(2010/11/28)
-
- METHOD FOR THE USE OF PYRANOINDOLE DERIVATIVES TO TREAT INFECTION WITH HEPATITIS C VIRUS
-
The invention is directed to methods of treating, preventing, or inhibiting a Hepatitis C viral infection in a mammal comprising containing the mammal with an effective amount of a compound of the formula: Wherein substitutions at R1, R2, R3-R12, and Y are set forth in the specification.
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