66 results about "BRD4" patented technology

The invention provides compositions comprising an effective amount of an agent that inhibits a BET protein (e.g., Brd2, Brd3, Brd4), and methods of using such compositions for treating or preventing metabolic syndrome, obesity, type II diabetes, insulin resistance, and related disorders characterized by undesirable alterations in metabolism or fat accumulation.

The present invention relates to an amorphous solid form of (4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(1H)-one, and processes for its preparation, which is an inhibitor of BET proteins such as BRD2, BRD3, BRD4, and BRD-t and is useful in the treatment of various diseases such as cancer.

The present invention relates to an amorphous solid form of (4S)-7-(3,5-dimethylisoxazol-4-yl)-4-pyridin-2-yl-4,5-dihydroimidazo[1,5,4-de][1,4]benzoxazin-2(M)-one, and processes for its preparation, which is an inhibitor of BET proteins such as BRD2, BRD3, BRD4, and BRD-t and is useful in the treatment of various diseases such as cancer.

The invention relates to the field of medicinal chemistry, in particular to pyrrolone derivatives, a preparation method of the pyrrolone derivatives, a pharmaceutical composition containing the compounds and medical purposes of the pharmaceutical composition, particularly an antitumor purpose of the pharmaceutical composition as a BRD4 protein inhibitor.

The invention discloses nitrogen-containing heterocyclic ring compounds, and a preparation method, pharmaceutical compositions and application thereof. The nitrogen-containing heterocyclic ring compounds as shown in a formula II which is described in the specification can effectively bind to the bromodomains of BRD4, BRD3, BRD2 and BRDT in the BET family so as to regulate the transcription of thedownstream gene c-myc and related target genes thereof, thereby regulating downstream signal pathways and playing specific roles, including treatment of diseases such as inflammatory diseases, cancersand AIDS; and a part of the compounds have high activity, and good cell activity and metabolic stability, and thus can be used as effective drugs for treating tumors.

The invention discloses applications of staurosporine compounds in preparing medicines for treating cancer, inflammation or AIDS. The compounds are obtained through separation and purification from actinomycetes, and are identified to be staurosporine compounds. The functional research shows that the compounds have relatively high activity for prostate cancer cells, and also have a relatively highinhibiting effect for Brd4 protein, and therefore, the compounds have good application prospects in preparing the medicines for treating tumor, HIV, leukemia and other diseases.

The invention discloses nitrogen-containing heterocyclic ring compounds, and a preparation method, pharmaceutical compositions and application thereof. The nitrogen-containing heterocyclic ring compounds as shown in a formula II which is described in the specification can effectively bind to the bromodomains of BRD4, BRD3, BRD2 and BRDT in the BET family so as to regulate the transcription of thedownstream gene c-myc and related target genes thereof, thereby regulating downstream signal pathways and playing specific roles, including treatment of diseases such as inflammatory diseases, cancersand AIDS; and a part of the compounds have high activity, and good cell activity and metabolic stability, and thus can be used as effective drugs for treating tumors.

The invention discloses a nitrogen-containing macrocyclic compound as well as a preparation method and a medicinal composition and application thereof. The invention provides the nitrogen-containing macrocyclic compound shown in the formula III-0, as well as a tautomer, an optical isomer, a hydrate, a solvent and pharmaceutical acceptable salts or predrug of the nitrogen-containing macrocyclic compound. The compound can be effectively combined with the bromodomain of BRD4, BRD3, BRD2 and BRDT in BET family so as to regulate and control the transcription of the downstream gene c-myc and relatedtarget genes thereof, and further a signaling pathway of the downstream is adjusted and a specific role is played, including treatment of diseases such as inflammatory diseases, cancer and AIDS (Acquired Immune Deficiency Syndrome). (The formula is shown in the description).

The invention relates to a pyridine N-oxidation derivative as well as a preparation method and an application thereof, in particular to a compound shown in a general formula (I), a preparation methodof the compound, pharmaceutical composition containing the compound and an application of the compound as a BRD4 inhibitor in treating related diseases such as cancer, inflammation, chronic liver diseases, diabetes, cardiovascular diseases, AIDS and the like, wherein in the general formula (I), all substituent groups are the same as definitions in the description.

The invention provides thiazoline compounds as shown in a general formula (I) and a pharmaceutical composition and application of the thiazoline compounds. The thiazoline compounds provided by the invention can be used for regulating the downstream signal passage and exerting the specific function after being bonded with a protein with a bromodomain structural domain and thus can be used for treating multiple diseases related to the protein with the bromodomain structural domain. The thiazoline compounds provided by the invention can be used for down regulating the transcription of a cancer gene c-myc and a related target gene by disturbing the bond of Brd4 with the bromodomain structural domain and an acetylated histone, thereby becoming the effective therapeutic drug of tumors.

The invention provides bivalent inhibitors of BET bromodomains, such as compounds of Formulae (I), (II), (III), (IV), (V) and (VI). Some bromdomain-containing proteins (e.g., BRD4) have a tandem bromodomain primary structure comprising more than one bromodomain binding site (e.g., BRD4 comprises BD1 and BD2). Bivalent inhibitors of BET bromodomains provided herein can target bromodomains through advantageous multivalent interactions, and therefore can be used to treat diseases or conditions associated with bromodomain-containing proteins. The present also provides pharmaceutical compositions and kits comprising the inventive compounds, as well as methods of using the inventive compounds.

The invention belongs to the technical field of bio-pharmaceuticals and relates to compounds accelerating duplication of a herpes simplex virus and an application. 9 known compounds are found capable of accelerating HSV duplication process, comprising JQ-1 (PubChem CID 46907787), PFI-1 (PubChem CID 71271629), I-BET-762 (PubChem CID 46943432), TG101348 (PubChem CID 16722836), Quisinostat (PubChem CID 11538455), CUDC-907 (PubChem CID 54575456), CUDC-101 (PubChem CID 24756910), Givinostat (PubChem CID 9804992) and HDAC-42 (PubChem CID 6918848). The compounds can increase virus infection to different extents and can be classified into histone deacetylase inhibitors (HDACi) or BET bromine domain proteins, for example BRD4 protein (Genbank accession NP_490597) bromodomain (bromodomain proteins) inhibitors. The compounds are drugs with ability of independently killing tumors and can be combined with HSV oncolytic viruses for tumor treatment and research.

BET protein-inhibitory, especially BRD2-, BRD3- and BRD4-inhibitory, 4-substituted pyrrolo- and pyrazolodiazepines of the general formula Iare described, in which X, Y, n, m, p, R1, R2, R3, R4 and R5 are each as defined in the description, as are pharmaceutical compositions comprising the inventive compounds, and the prophylactic and therapeutic use thereof in the case of hyperproliferative disorders, especially in the case of neoplastic disorders. Also described is the use of the inventive compounds as BET protein inhibitors in benign hyperplasias, in atherosclerotic disorders, in sepsis, in autoimmune disorders, in vascular disorders, in viral infections, in neurodegenerative disorders, in inflammatory disorders and in male fertility control.

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.

The invention relates to the technical field of medicines, in particular to an application of a bromodomain protein 4 (BRD4) inhibitor JQ1 or a derivative thereof in preparation of a medicine for treating sepsis intestinal barrier injury. Experiments show that in a lipopolysaccharide (LPS)-induced sepsis mouse intestinal barrier injury model, the BRD4 inhibitor JQ1 can effectively inhibit LPS-induced sepsis mouse intestinal mucosa damage, release of inflammatory factors TNF[alpha], IL1[beta] and IL18, release of NLRP3 complex inflammasome, and high expression of pyroptosis marker genes GSDMD,GSDME, P2X7 and Aim2. Results show that the BRD4 inhibitor JQ1 can effectively prevent the sepsis mouse intestinal barrier injury by inhibiting intestinal tissue cell pyroptosis, and can be used for preparing a pharmaceutical preparation for treating the sepsis intestinal barrier injury.

The invention relates to the field of medicine chemicals, in particular relates to a dihydropteridine ketone type BRD4 (Bromodomain-Containing Protein 4) protein inhibitor as well as a preparation method and application thereof, and particularly application as BRD4 protein inhibitors and antitumor medicines. The compound has a structural formula as shown in the specification.

The present invention relates to the use of NSD3i inhibitors for the treatment of cancer. In particular, the present invention relates to methods, kits and compositions comprising NSD3 inhibitors to treat cancers dependent on NSD3, in particular subjects with NUT midline carcinoma (NMC) and subjects with NSD3 / NUT or BRD4 / NUT or BRD3 / NUT fusion genes, as well as subjects with BRD4-dependent (but NUT-independent cancers). The present invention also relates to methods, kits and compositions comprising BET inhibitors for the treatment of subjects with NSD3 / NUT fusion genes. Other aspects of the invention relate to assays and methods to identify an inhibitor of NSD3 which disrupts or decreases the interaction of the NSD3 protein with the ET do main of BRD4.

The present invention provides a polycyclic compound represented by formula (I) and a use in dual inhibitors of AR and BET. Specifically, the present invention provides the use of a compound represented by formula (I) or optical isomers, solvates, pharmaceutically acceptable salts, prodrugs, tautomers, mesomers, racemates, enantiomers, diastereomers, mixture form, metabolites, metabolic precursorsor isotopic substitution form thereof in the preparation of dual inhibitors of AR and BET. Experimental results show that the compounds of the present invention can not only inhibit the transcriptionof PSA and FKBP5 downstream of AR, but also inhibit the transcriptional activity of AR-F876L mutants resistant to anthralin, and also downregulate the expression of BRD4 downstream protein c-Myc, andthe compounds have good binding affinity to AR and BET proteins. The experiment suggests that the compound of the present invention can inhibit the activity of AR and BET protein at the same time, and has a good application prospect in the preparation of medicine for preventing and / or treating diseases related to BET protein.

The invention discloses gene markers for forecasting an immunotherapy effect on a cancer and application of the gene markers. The markers comprise BRD4, RPS6KA4, TET1, BCL10, FGFR2, RAD51C, TCF7L2, TGFBR1, AR, BBC3, H3C11, TSC2, NSD1, PNRC1, IGF2, H3C3, SOCS1, TCF3, TSHR, PMS2, EGFR and CDKN2A. According to the application, a model constructed by 22 genes can be used for predicting an immunotherapy effect and better instructing clinical medication, and the susceptibility and specificity of prediction of the model are superior to those of PD-L1 expression.

The invention provides isatin compounds as well as a preparation method and an application thereof. The compounds have the structure shown in a formula (I) and have good BRD4 protein inhibition activity, have huge application potential in the antitumor and anti-virus aspects and can be applied to preparation of BRD4 inhibitor drugs; meanwhile, the compounds have good HIV latent virus activation capability, have greatly reduced in-vitro cytotoxicity as compared with known HIV latent activators JQ1, are safer to use and have good tolerance.

The invention relates to a salt of a bromine domain structural protein inhibitor as well as a preparation method and application thereof. The invention belongs to the field of biological medicines, and relates to the salt and a crystal form of the bromine domain structural protein inhibitor as well as the preparation method and application thereof. The invention particularly relates to an acid addition salt and an acid addition salt crystal form of a compound shown as a general formula (I), a preparation method and application of a pharmaceutical composition containing a therapeutically effective amount of the salt or the crystal form. The invention discloses application of the compound serving as a BRD4 high-selectivity inhibitor to treatment of cardiovascular diseases such as cancer, inflammation, chronic liver diseases, diabetes and dyslipidemia or related diseases such as AIDS, wherein substituents in the formula (I) are as defined in the claims.

The invention discloses BRD4 protein targeting anti-tumor polypeptide and application thereof, and a microarray screening method has the advantages of small raw material consumption, high flux and small error. The polypeptide targeting the BRD4-BD1 / BRD4-BD2 structural domain based on high-throughput screening has the advantages of high affinity and high selectivity, and the effect of the polypeptide in detection or treatment of cancers. The polypeptide has the characteristics of high affinity and strong specificity. In addition, a high-affinity and high-selectivity polypeptide sequence for screening the BRD4 protein by using a one-bead-one-peptide technology is created for the first time. According to the method, a polypeptide compound library which has no preference and is diverse in variety can be rapidly established, and the defects that a traditional screening method is tedious in steps, low in screening experiment speed and low in efficiency are overcome.

The invention provides dihydropteridinone-sulfamide derivatives as well as a preparation method and application thereof aiming at problems in the prior art, and provides a novel choice for developmentof an antitumor drug for inhibiting a bromodomain (BRD4) protein. Activity experiments confirm that the novel compounds having the dihydropteridinone structure provided by the invention have a good inhibitory effect on the BRD4 protein and can inhibit proliferation of tumor cells, especially for gastric cancer cells, and the inhibitory activity of partial compounds reaches or is superior to thatof a positive control compound JQ1; and the derivatives provided by the invention provide a novel drug choice for a BRD4 inhibitor and treatment of diseases such as tumors.

The invention discloses a dual HDAC / BRD4 inhibitor and a preparation method and application thereof .The structural formula of the dual HDAC / BRD4 inhibitor is shown in the formula 16 .The invention further discloses a preparation method of the dual HDAC / BRD4 inhibitor and application of the dual HDAC / BRD4 inhibitor in preparing medicine .A pharmacophore of an HDAC inhibitor and a pharmacophore of a BRD4 inhibitor are spliced through a linker, and therefore the novel dual HDAC / BRD4 inhibitor with a dual HDAC / BRD4 inhibiting effect is obtained .The preparation method is simple, mild in condition and easy to implement .

The invention relates to an aromatic amine compound and application thereof in the preparation of AR and BRD4 dual inhibitors and regulators. Specifically, the invention provides a compound shown as aformula I, and the compound has dual inhibition effects on AR and BRD4. The compound not only can inhibit proliferation of prostate cancer cell lines LNCaP / AR with multiple expression of androgen receptor AR, but also shows a good inhibition effect on prostate cancer cell lines VCaP and 22RV1, which are resistant to prostate cancer drugs (enzalutamide) on the market. The compound is used as a compound capable of simultaneously identifying AR and BRD4 double targets; can be used as an AR / BRD4 dual inhibitor, can also be used for preparing protein degradation targeting chimeras (PROTACs) for inducing AR / BRD4 dual-target degradation, and has a good application prospect in preparation of drugs for treating AR and BRD4 related diseases.

The invention discloses an aromatic-ring-containing compound, a preparation method thereof, a pharmaceutical composition and application. The present invention provides the aromatic-ring-containing compound represented by a formula 1, a pharmaceutically acceptable salt thereof, a stereoisomer thereof, a tautomer thereof or a solvate thereof, and the aromatic-ring-containing compound can be effectively bounded to bromodomains of BRD4, BRD3, BRD2, and BRDT in BET family to regulate transcription of downstream gene c-myc and related target genes of the c-myc so as to regulate downstream signalingpathways to play specific roles including treatment of diseases such as inflammatory diseases, cancer, and AIDS. Some of the compounds have high activity, and have good cell activity and metabolic stability, so that the compounds can be an effective drug for treating tumors.

The invention belongs to the technical field of medicine, particularly relates to a BRD4 protein inhibitor shown in the general formula (I), acceptable salt, hydrolysable ester, isomer and intermediate in pharmacy, and a preparation method of the compounds and intermediate. The BRD4 protein inhibitor can be used for preparing a drug for treating and / or preventing tumors. R1, R2, R3, R4, R5, A, B, C, D, Q, m and n are defined in the description. The general formula (I) is shown in the description.

The invention provides an indole compound which has a structure as shown in a formula I. The invention also provides a preparation method and application of the compound shown in the formula I. The compound as shown in the formula I has excellent inhibitory activity on BRD4 protein and has potential application value in preparation of drugs for treating tumors.