1-(2-chloro-5-(hydroxymethyl)pyridin-4-yl)-3-(3-(difluoromethyl)isothiazol-5-yl)urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(2-chloro-5-(hydroxymethyl)pyridin-4-yl)-3-(3-(difluoromethyl)isothiazol-5-yl)urea
• 英文别名: 1-[2-Chloro-5-(hydroxymethyl)pyridin-4-yl]-3-[3-(difluoromethyl)-1,2-thiazol-5-yl]urea；1-[2-chloro-5-(hydroxymethyl)pyridin-4-yl]-3-[3-(difluoromethyl)-1,2-thiazol-5-yl]urea
• 化学式: C₁₁H₉ClF₂N₄O₂S
• 分子量: 334.734
• InChiKey: AVHFGSYJGSZHIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4,6-二氯烟酸甲酯 在 吡啶 、 咪唑 、 lithium aluminium tetrahydride 、 四丁基氟化铵 、 三乙胺 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 120.0h， 生成 1-(2-chloro-5-(hydroxymethyl)pyridin-4-yl)-3-(3-(difluoromethyl)isothiazol-5-yl)urea
  参考文献：
  名称：

  WO2020035779A5

  摘要：

  公开号：

  WO2020035779A5

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。
• Discovery of Orally Active Inhibitors of Brahma Homolog (BRM)/SMARCA2 ATPase Activity for the Treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers
  作者：Julien P. N. Papillon、Katsumasa Nakajima、Christopher D. Adair、Jonathan Hempel、Andriana O. Jouk、Rajeshri G. Karki、Simon Mathieu、Henrik Möbitz、Rukundo Ntaganda、Troy Smith、Michael Visser、Susan E. Hill、Felipe Kellermann Hurtado、Gregg Chenail、Hyo-Eun C. Bhang、Anka Bric、Kay Xiang、Geoffrey Bushold、Tamara Gilbert、Anthony Vattay、Julie Dooley、Emily A. Costa、Isabel Park、Ailing Li、David Farley、Eugen Lounkine、Q. Kimberley Yue、Xiaoling Xie、Xiaoping Zhu、Raviraj Kulathila、Daniel King、Tiancen Hu、Katarina Vulic、John Cantwell、Catherine Luu、Zainab Jagani

  DOI：10.1021/acs.jmedchem.8b01318

  日期：2018.11.21

  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.
• UREA COMPOUNDS AND COMPOSITIONS AS SMARCA2/BRM ATPASE INHIBITORS
  申请人：Novartis AG

  公开号：US20210323956A1

  公开（公告）日：2021-10-21

  A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a BRM-mediated and/or BRG1-mediated disease or disorder: Formula (I) wherein R 1 through R 6 are as defined herein.
• 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.