3-((4-(3-(2-chloropyridin-4-yl)ureido)pyridin-2-yl)ethynyl)benzoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-((4-(3-(2-chloropyridin-4-yl)ureido)pyridin-2-yl)ethynyl)benzoic acid
• 英文别名: 3-[(4-{[(2-Chloropyridin-4-yl)carbamoyl]amino}pyridin-2-yl)ethynyl]benzoic acid；3-[2-[4-[(2-chloropyridin-4-yl)carbamoylamino]pyridin-2-yl]ethynyl]benzoic acid
• 化学式: C₂₀H₁₃ClN₄O₃
• 分子量: 392.801
• InChiKey: ATBXCKLXXDLBAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(8-aminooctyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamide 、 3-((4-(3-(2-chloropyridin-4-yl)ureido)pyridin-2-yl)ethynyl)benzoic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.08h， 以6%的产率得到3-[2-[4-[(2-chloropyridin-4-yl)carbamoylamino]pyridin-2-yl]ethynyl]-N-[8-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]octyl]benzamide
  参考文献：
  名称：

  [EN] COMPOUNDS, COMPOSITIONS, AND METHODS FOR PROTEIN DEGRADATION
  [FR] COMPOSÉS, COMPOSITIONS ET PROCÉDÉS DE DÉGRADATION DE PROTÉINES

  摘要：

  Disclosed herein are compounds that target SMARCA2, SMARCA4 or BRM, causing their degradation. Also disclosed herein are compositions and methods of use in treating associated disorders and diseases.

  公开号：

  WO2021163302A1
• 作为产物：
  描述：

  3-乙炔基苯甲酸甲酯 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 21.92h， 生成 3-((4-(3-(2-chloropyridin-4-yl)ureido)pyridin-2-yl)ethynyl)benzoic acid
  参考文献：
  名称：

  Discovery of Orally Active Inhibitors of Brahma Homolog (BRM)/SMARCA2 ATPase Activity for the Treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers

  摘要：

  SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), is a Snf2-family DNA-dependent ATPase. BRM and its close homologue Brahma-related gene 1 (BRG1), also known as SMARCA4, are mutually exclusive ATPases of the large ATP-dependent SWI/SNF chromatin-remodeling complexes involved in transcriptional regulation of gene expression. No small molecules have been reported that modulate SVVI/SNF chromatin-remodeling activity via inhibition of its ATPase activity, an important goal given the well-established dependence of BRG1-deficient cancers on BRM. Here, we describe allosteric dual BRM and BRG1 inhibitors that downregulate BRM-dependent gene expression and show antiproliferative activity in a BRG1-mutant-lung-tumor xenograft model upon oral administration. These compounds represent useful tools for understanding the functions of BRM in BRG1-loss-of-function settings and should enable probing the role of SWI/SNF functions more broadly in different cancer contexts and those of other diseases.

  DOI：

  10.1021/acs.jmedchem.8b01318

文献信息

• [EN] METHODS OF TREATING CANCERS<br/>[FR] MÉTHODES DE TRAITEMENT DE CANCERS
  申请人：FOGHORN THERAPEUTICS INC

  公开号：WO2021236080A1

  公开（公告）日：2021-11-25

  The present invention relates to methods and compositions for the treatment of BAF-related disorders such as acute myeloid leukemia. The present invention features methods to treat AML, e.g., in a subject in need thereof. In one aspect, the invention features a method of treating AML in a subject in need thereof, the method including administering to the subject an effective amount of an agent that reduces the level and/or activity of BRG1 and/or BRM.

  本发明涉及用于治疗与BAF相关的疾病，如急性髓系白血病的方法和组合物。本发明涉及治疗AML的方法，例如，在需要的受试者中。在一个方面，本发明涉及一种治疗需要的受试者AML的方法，该方法包括向受试者施用能够减少BRG1和/或BRM水平和/或活性的药剂的有效量。
• [EN] SMARCA DEGRADERS AND USES THEREOF<br/>[FR] AGENTS DE DÉGRADATION DE SMARCA ET LEURS UTILISATIONS
  申请人：KYMERA THERAPEUTICS INC

  公开号：WO2020251971A1

  公开（公告）日：2020-12-17

  The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same for the modulation of one or more SWI/SNF-related matrix associated actin dependent regulator of chromatin subfamily A (SMARCA) and/or polybromo-1 (PB-1) protein via ubiqitination and/or degradation by compounds. The compounds are bifunctional molecules that link a cereblon-binding moiety to a ligand that binds SMARCA and/or PB1 proteins.

  本发明提供化合物、其药学上可接受的组合物，以及利用这些化合物调控一个或多个SWI/SNF相关基质相关肌动蛋白依赖的染色质亚家族A（SMARCA）和/或聚溴-1（PB-1）蛋白通过化合物的泛素化和/或降解的方法。这些化合物是双功能分子，将结合到cereblon的部分与结合到SMARCA和/或PB1蛋白的配体连接在一起。
• METHODS OF TREATING CANCERS
  申请人：Foghorn Therapeutics Inc.

  公开号：US20220016083A1

  公开（公告）日：2022-01-20

  The present invention relates to methods and compositions for the treatment of BAF-related disorders such as melanoma, prostate cancer, breast cancer, bone cancer, renal cell carcinoma, and hematologic cancer.
• [EN] UREA DERIVATIVES<br/>[FR] DÉRIVÉS D'URÉE
  申请人：BAYER AG

  公开号：WO2020126968A2

  公开（公告）日：2020-06-25

  The present invention covers urea compounds of general formula (I) in which R1, A and B are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of hyperproliferative disorders, as a sole agent or in combination with other active ingredients.