- 4-ARYLQUINAZOLINE DERIVATIVES AS INHIBITORS OF METHIONINE ADENOSYLTRANSFERASE 2A
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The invention relates to certain derivatives of 4-arylquinazoline formula (I) which are inhibitors of methionine adenosyltransferase 2A (MAT2A). The invention also relates to pharmaceutical compositions comprising such compounds and methods of treating diseases that can be treated by inhibition of MAT2A such as cancer, including cancers characterized by reduced or no activity of methylthioadenosine phosphorylase (MTAP).
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Paragraph 0261
(2021/12/31)
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- Preparation method of 2-amino-3-methoxy-5-bromobenzonitrile
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The invention discloses a preparation method of 2-amino-3-methoxy-5-bromobenzonitrile. The method comprises the following steps: (1) reacting a compound (II) with sodium methoxide to generate a compound (III); (2) carrying out reduction treatment on the compound (III) to obtain a compound (IV); (3) reacting the compound (IV) with trichloroacetaldehyde hydrate and hydroxylamine hydrochloride to generate a compound (V); (4) reacting the compound (V) with concentrated sulfuric acid to generate a compound (VI); (5) preparing a compound (VII) from the compound (VI) under the conditions of hydrogenperoxide and sodium hydroxide; (6) reacting the compound (VII) with acyl chloride to generate a compound (VIII); (7) reacting the compound (VIII) with ammonia water to generate a compound (IX); and (8) reacting the compound (IX) in the presence of phosphorus pentoxide to generate 2-amino-3-methoxy-5-bromobenzonitrile. The preparation method provided by the invention is higher in yield.
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Paragraph 0032; 0042-0043; 0052; 0062-0063; 0070; 0080-0081
(2021/02/10)
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- QUINAZOLINE COMPOUND AND PREPARATION METHOD, APPLICATION, AND PHARMACEUTICAL COMPOSTION THEREOF
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The invention relates to quinazoline compounds, the preparation method, use, and the pharmaceutical composition thereof. The said quinazoline compounds, which are represented by Formula (I), are phosphatidylinositol 3-kinase (PI3K) inhibitors, and can be applied to prevent and/or treat PI3K activity-related diseases, such as cancer, immune diseases, cardiovascular diseases, viral infections, inflammation, metabolism/endocrine function disorders or neurological diseases.
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Paragraph 0084; 0085
(2019/11/14)
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- Discovery and Optimization of 2-Amino-4-methylquinazoline Derivatives as Highly Potent Phosphatidylinositol 3-Kinase Inhibitors for Cancer Treatment
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Increased phosphatidylinositol 3-kinase (PI3K) signaling is among the most common alterations in cancer, spurring intensive efforts to develop new cancer therapeutics that target this pathway. In this work, we discovered a series of novel 2-amino-4-methylquinazoline derivatives through a hybridization and subsequent scaffold hopping approach that were highly potent class I PI3K inhibitors. Lead optimization resulted in several promising compounds (e.g., 19, 20, 37, and 43) with nanomolar PI3K potencies, prominent antiproliferative activities, favorable PK profiles, and robust in vivo antitumor efficacies. More interestingly, compared with 19 and 20, 37 and 43 demonstrated improved brain penetration and in vivo efficacy in an orthotopic glioblastoma xenograft model. Furthermore, preliminary safety assessments including hERG channel inhibition, AMES, CYP450 inhibition, and single-dose toxicity were performed to characterize their toxicological properties.
- Lin, Songwen,Wang, Chunyang,Ji, Ming,Wu, Deyu,Lv, Yuanhao,Zhang, Kehui,Dong, Yi,Jin, Jing,Chen, Jiajing,Zhang, Jingbo,Sheng, Li,Li, Yan,Chen, Xiaoguang,Xu, Heng
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p. 6087 - 6109
(2018/07/05)
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- CERTAIN CHEMICAL ENTITIES, COMPOSITIONS, AND METHODS
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Chemical entities that are kinase inhibitors, pharmaceutical compositions and methods of treatment of cancer are described.
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Paragraph 0288; 0411
(2018/03/09)
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- COMBINATION THERAPIES FOR TREATMENT OF CANCER
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Combination therapies for treatment of cancers associated with mutations in the KRAS gene are provided. Compositions comprising therapeutic agents for treatment of cancers associated with mutations in the KRAS gene are also provided.
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Paragraph 303; 304
(2016/04/09)
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- Discovery, synthesis, and biological evaluation of thiazoloquin(az)olin(on)es as potent CD38 inhibitors
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A series of thiazoloquin(az)olinones were synthesized and found to have potent inhibitory activity against CD38. Several of these compounds were also shown to have good pharmacokinetic properties and demonstrated the ability to elevate NAD levels in plasm
- Haffner, Curt D.,Becherer, J. David,Boros, Eric E.,Cadilla, Rodolfo,Carpenter, Tiffany,Cowan, David,Deaton, David N.,Guo, Yu,Harrington, Wallace,Henke, Brad R.,Jeune, Michael R.,Kaldor, Istvan,Milliken, Naphtali,Petrov, Kim G.,Preugschat, Frank,Schulte, Christie,Shearer, Barry G.,Shearer, Todd,Smalley, Terrence L.,Stewart, Eugene L.,Stuart, J. Darren,Ulrich, John C.
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p. 3548 - 3571
(2015/05/05)
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- COVALENT INHIBITORS OF KRAS G12C
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Irreversible inhibitors of G12C mutant K-Ras protein are provided. Also disclosed are methods to modulate the activity of G12C mutant K-Ras protein and methods of treatment of disorders mediated by G12C mutant K-Ras protein.
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Paragraph 0511
(2014/09/30)
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- NEW CHEMICAL COMPOUNDS
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The present invention encompasses compounds of general formula (1) while the groups R4 to R7 and the units W, L, Qa and QH are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use as medicaments having the above-mentioned properties.
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Page/Page column 78
(2010/04/03)
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- NEW CHEMICAL COMPOUNDS
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The present invention encompasses compounds of general formula (1) wherein the units W, A, L, Q1 and QH are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, and their use as medicaments having the above-mentioned properties.
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Page/Page column 112
(2010/04/03)
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- Dual Pharmacophores - PDE4-Muscarinic Antagonistics
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The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.
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Page/Page column 50
(2009/08/18)
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- Dual Pharmacophores - PDE4-Muscarinic Antagonistics
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The present invention relates to novel compounds of Formula (I) and their use in the treatment of respiratory diseases, including anti-inflammatory and allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.
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Page/Page column 53
(2009/08/18)
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- Dual Pharmacophores - PDE4-Muscarinic Antagonistics
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The present invention is directed to novel compounds of Formula (I), pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of/and or prophylaxis of respiratory diseases, including antiinflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.
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Page/Page column 52-53
(2009/08/16)
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- DUAL PHARMACOPHORES - PDE4-MUSCARINIC ANTAGONISTICS
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The present invention is directed to novel compounds of Formula's (I) - (VI), and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of and/or prophylaxis of respiratory diseases, including inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.
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Page/Page column 131
(2009/10/09)
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