- Heterocyclic compounds as BCL-2 inhibitor
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The present invention relates to a compound, a pharmaceutical composition containing the same, preparation method of the compound and thepharmaceutical composition, and uses ofthe compound and the pharmaceutical compositionas B-cell lymphoma-2 (BCL-2) inhibitors, wherein the compound is a compound shown as a formula I, or an isomer, a prodrug, a solvate, a stable isotope derivative or a pharmaceutically acceptable salt thereof. The invention also relates to the uses of the compound or the composition containing the same in treatment or prophylaxis of BCL2-mediated related diseases such as tumours.
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Paragraph 0093
(2021/04/17)
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- Preparation method of Venetoclax intermediate and product
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The invention discloses a preparation method of a Venetoclax intermediate. 5-bromine-7-azaindole (II) is used as a raw material; an upper protecting group generates 5-bromine-1-(Triisopropyl silicyl)-1H-pyrrolo[2,3-b]pyridine (III); a compound (III) and T
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Paragraph 0040; 0047-0049; 0050; 0057-0059
(2019/02/25)
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- Solid dispersions containing an apoptosis-inducing agent
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A pro-apoptotic solid dispersion comprises, in essentially non-crystalline form, a Bcl-2 family protein inhibitory compound of Formula I as defined herein, dispersed in a solid matrix that comprises (a) a pharmaceutically acceptable water-soluble polymeric carrier and (b) a pharmaceutically acceptable surfactant. A process for preparing such a solid dispersion comprises dissolving the compound, the polymeric carrier and the surfactant in a suitable solvent, and removing the solvent to provide a solid matrix comprising the polymeric carrier and the surfactant and having the compound dispersed in essentially non-crystalline form therein. The solid dispersion is suitable for oral administration to a subject in need thereof for treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.
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Page/Page column 12-13
(2019/03/15)
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- Bcl-2 INHIBITORS
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Disclosed herein is a compound of Formula (I) for inhibiting Bcl-2 and treating disease associated with undesirable bcl-2 activity (Bcl-2 related diseases), a method of using the compounds disclosed herein for treating dysregulated apoptotic diseases including cancers and treating autoimmune disease, and a pharmaceutical composition comprising the same.
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Paragraph 1116; 1117; 1454; 1455
(2019/11/19)
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- PROCESS FOR THE PREPARATION OF VENETOCLAX
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The present disclosure provides novel synthetic process for the preparation of venetoclax. The disclosed processes involve the use of novel intermediates. Processes for the preparation of these intermediates are also disclosed as well as methods for the preparation of particularly useful salts thereof.
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- N-benzenesulfonyl benzamide compound for inhibiting Bcl-2 proteins as well as composition and application thereof
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The invention relates to a compound capable of inhibiting the activity of Bcl-2 anti-apoptosis protein as well as a preparation and application thereof, in particular to an N-benzenesulfonyl benzamidecompound for inhibiting Bcl-2 proteins as shown in formula (I), or a medicine composition of a crystal form, a precursor, a pharmaceutically-acceptable salt, a three-dimensional isomer, a solvent composition or a hydrate of the N-benzenesulfonyl benzamide compound. The compound and the composition containing the compound have excellent rejection capability for Bcl-2 proteins, have better pharmacokinetics parameter characteristics, can increase the medicine concentration of the compound in animal bodies, and can improve the drug curative effect and safety. (The formula (I) is shown in the description).
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Paragraph 0110; 0111; 0112
(2018/11/03)
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- Compound, preparation method and applications thereof
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The invention relates to a new diaryl ether alkynyl compound I and a synthesis method thereof, provide a synthesis method for obtaining a compound II from the compound I through a cyclization reaction, and relates to the field of pharmaceutical intermediate synthesis. According to the present invention, the synthesis of an anticancer drug key intermediate is completed through the designed completely-new synthesis path; and the synthesis method comprises the coupling reaction between the aryl group and the terminal alkyne and the cyclization reaction of the five-membered nitrogen-containing heterocyclic ring, and has characteristics of easily available raw materials, mild reaction conditions, and simple operation.
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- A ABT - 199 intermediate preparation method (by machine translation)
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The invention discloses a ABT - 199 intermediate preparation method, the intermediate structure correspond to the formula I: The method comprises the compound of formula II 5 - bromo - 7 - azaindole as raw materials, through the protection, copper catalytic hydroxylation reaction, substituted, to protect 4 step reaction, the final formula I of ABT - 199 intermediate. The method of the invention cheap raw material, mild reaction conditions, the problem of non-selective, high yield, is more suitable for industrial production. (by machine translation)
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- Preparation method of ABT-199 intermediate
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The invention discloses a preparation method of an ABT-199 intermediate. The structure of the intermediate corresponds to a formula XI (shown in the description). The preparation method comprises the steps of carrying out seven reaction steps of condensation, elimination, addition, cyclization, deprotection, hydrolysis and reesterification on a compound of formula I, namely 4-methyl fluorosalicylate, so as to finally obtain the ABT-199 intermediate of the formula XI. The preparation method has the beneficial effects that the raw materials are cheap and easily available, reaction conditions are mild, the selective problem is avoided, and the yield is relatively high; and the preparation method is more applicable to industrial production.
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Paragraph 0069; 0109; 0110; 0111; 0112; 0113-0115; 0156-0162
(2017/10/22)
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- Synthesis method for BCL-2 inhibitor Venetoclax
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The invention discloses a new synthesis method for a BCL-2 inhibitor Venetoclax. The synthesis method includes the steps that 2,4-difluoro methyl benzoate serves as a raw material, the 2,4-difluoro methyl benzoate and 5-hydroxy-7-azaindole are subjected to a condensation reaction, Ven-16 is obtained, and 4-substituted isomer and other impurities are removed through recrystallization; the product and N-Boc-piperazine are reacted and hydrolyzed, and Ven-18 is obtained; Ven-18 and Ven-21 are condensed, Boc of trifluoroacetic acid is removed, and Ven-20 is obtained; the product and Ven-7 are reacted, reaction intermediates in all the steps have the good crystal forms, purification can be carried out through crystal to achieve the center control requirements of the technology, and a final product Venetoclax can also be subjected to recrystallization to obtain the product Venetoclax, wherein the HPLC purity of the Venetoclax is larger than 99.5%, and the individual impurity of the Venetoclax is smaller than 0.1%; the Venetoclax has the industrialized application value.
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Paragraph 0033; 0034; 0035; 0036
(2017/09/26)
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- Sulfonamide derivative and application thereof in pharmacy
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The invention relates to a sulfonamide derivative and a pharmaceutical composition containing the same, and an application of the sulfonamide derivative and the pharmaceutical composition of the sulfonamide derivative in drug preparation, specifically the application in drug preparation of a BCL-2 family protein antagonist and the application in treatment of cancers.
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Paragraph 0188; 0189; 0190
(2017/05/02)
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- SOLID FORMS OF VENETOCLAX AND PROCESSES FOR THE PREPARATION OF VENETOCLAX
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Aspects of the present application relate to solid forms of Venetoclax and preparative processes thereof. Specific aspects relate to an amorphous form of Venetoclax, its solid dispersion and crystalline forms of Venetoclax or salts thereof. Further aspects of the present application relate to processes for the preparation of Venetoclax.
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Page/Page column 57; 58
(2018/01/19)
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- THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR, AND/OR A BCL-2 INHIBITOR
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Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.
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Paragraph 00746
(2016/02/29)
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- APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
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Disclosed herein are compounds that inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases using the compounds.
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Paragraph 0228
(2014/09/30)
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- SALTS AND CRYSTALLINE FORMS OF AN APOPTOSIS-INDUCING AGENT
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Salts and crystalline forms of 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}- sulfonyl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide are suitable active pharmaceutical ingredients for pharmaceutical compositions useful in treatment of a disease characterized by overexpression of one or more anti-apoptotic Bcl-2 family proteins, for example cancer.
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Page/Page column 11
(2012/06/15)
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- APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
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Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.
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Page/Page column 80
(2011/12/14)
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- APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
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Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.
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Page/Page column 56
(2010/08/07)
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- APOPTOSIS INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
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Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.
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Page/Page column 119
(2010/12/29)
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