SB1317（TG02）抑制剂 | 1204918-72-8

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: SB1317（TG02）抑制剂
• 英文名称: TG02
• 英文别名: SB 1317；zotiraciclib；(16E)-14-methyl-20-oxa-5,7,14,27-tetrazatetracyclo[19.3.1.12,6.18,12]heptacosa-1(25),2(27),3,5,8,10,12(26),16,21,23-decaene
• CAS: 1204918-72-8
• 化学式: C₂₃H₂₄N₄O
• 分子量: 372.47
• InChiKey: VXBAJLGYBMTJCY-NSCUHMNNSA-N

物化性质

• 溶解度：
  DMSO：26.5 mg/mL（71.15 mM；需要超声波和加热）

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  50.3
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  SB1317（TG02）抑制剂 在 盐酸 作用下， 以 水 为溶剂， 以78%的产率得到SB 1317 dihydrochloride
  参考文献：
  名称：

  Discovery of Kinase Spectrum Selective Macrocycle (16E)-14-Methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a Potent Inhibitor of Cyclin Dependent Kinases (CDKs), Janus Kinase 2 (JAK2), and Fms-like Tyrosine Kinase-3 (FLT3) for the Treatment of Cancer

  摘要：

  Herein, we describe the design, synthesis, and SAR of a series of unique small molecule macrocycles that show spectrum selective kinase inhibition of CDKs, JAK2, and FLT3. The most promising leads were assessed in vitro for their inhibition of cancer cell proliferation, solubility, CYP450 inhibition, and microsomal stability. This screening cascade revealed 26h as a preferred compound with target IC50 of 13, 73, and 56 nM for CDK2, JAK2 and FLT3, respectively. Pharmacokinetic (PK) studies of 26h in preclinical species showed good oral exposures. Oral efficacy was observed in colon (HCT-116) and lymphoma (Ramos) xenograft studies, in line with the observed PK/PD correlation. 26h (SB1317/TG02) was progressed into development in 2010 and is currently undergoing phase 1 clinical trials in advanced leukemias and multiple myeloma.

  DOI：

  10.1021/jm201112g
• 作为产物：
  描述：

  3-羟基苯硼酸 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 盐酸 、 四(三苯基膦)钯 、 caesium carbonate 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 4.0h， 生成 SB1317（TG02）抑制剂
  参考文献：
  名称：

  Acid Mediated Ring Closing Metathesis: A Powerful Synthetic Tool Enabling the Synthesis of Clinical Stage Kinase Inhibitors

  摘要：

  强大的烯烃转化反应被用于合成晚期临床药剂SB1317和SB1518。在这两种情况下，环戊烯烃开环反应似乎只在酸的存在下进行，并主要生成反异构体。对于SB1518，它在HCl酸的存在下进行，而对于SB1317，主要在三氟乙酸（TFA）的存在下进行。

  DOI：

  10.2533/chimia.2015.142

文献信息

• HETEROALKYL LINKED PYRIMIDINE DERIVATIVES
  申请人：Blanchard Stephanie

  公开号：US20090258886A1

  公开（公告）日：2009-10-15

  The present invention relates to pyrimidine compounds that are useful as anti-proliferative agents. More particularly, the present invention relates to heteroalkyl linked and substituted pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders. These compounds may be useful as medicaments for the treatment of a number of proliferative disorders including tumours and cancers as well as other conditions or disorders associated with kinases.

  本发明涉及用作抗增殖剂的嘧啶化合物。更具体地说，本发明涉及杂原子烷基连接和取代的嘧啶化合物，其制备方法，含有这些化合物的制药组合物以及在治疗增殖性疾病中使用这些化合物的用途。这些化合物可能作为药物对许多增殖性疾病，包括肿瘤和癌症以及与激酶相关的其他疾病或疾病的治疗有用。
• Polymorphic form of TG02
  申请人：Tragara Pharmaceuticals, Inc.

  公开号：US20190055263A1

  公开（公告）日：2019-02-21

  The present disclosure provides crystalline polymorphic forms of TG02 free base and TG02 acid addition salts, pharmaceutical compositions comprising crystalline polymorphic forms of TG02 free base and TG02 acid addition salts, and methods of treating cancer and other diseases in a patient with crystalline polymorphic forms of TG02 free base and TG02 acid addition salts.

  本公开提供了TG02游离基和TG02酸盐加成盐的晶态多态形式，包括晶态多态形式的TG02游离基和TG02酸盐加成盐的药物组合物以及使用晶态多态形式的TG02游离基和TG02酸盐加成盐治疗癌症和其他疾病的方法。
• Formylated N-heterocyclic derivatives as FGFR4 inhibitors
  申请人：Buschmann Nicole

  公开号：US10189813B2

  公开（公告）日：2019-01-29

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing said compound, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition comprising said compound.

  本发明提供了一种式（I）化合物或其药学上可接受的盐； 一种制造所述化合物的方法及其治疗用途。本发明进一步提供了一种药理活性剂组合和包含所述化合物的药物组合物。
• Aza-indazole compounds for use in tendon and/or ligament injuries
  申请人：NOVARTIS AG

  公开号：US10766894B2

  公开（公告）日：2020-09-08

  The present invention provides a compound of formula (I) in free form or in pharmaceutically acceptable salt form, a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了游离形式或药学上可接受的盐形式的式 (I) 化合物、制造本发明化合物的方法及其治疗用途。本发明进一步提供了药理活性剂的组合和药物组合物。
• Use of TG02 for treating gliomas in pediatric subjects
  申请人：UNIVERSITY OF PITTSBURGH—OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

  公开号：US11173160B2

  公开（公告）日：2021-11-16

  The present disclosure relates to uses of TG02, for treating a glioma in a pediatric human subject. In certain embodiments, the glioma can be a pediatric high-grade glioma (PHGG), e.g., a diffuse intrinsic pontine glioma (DIPG), and/or a H3.3-mutated glioma (e.g., a H3K27M-mutated glioma). The present disclosure further provides pharmaceutical compositions and kits that include an ERK5 inhibitor.

  本公开涉及TG02治疗小儿神经胶质瘤的用途。在某些实施方案中，胶质瘤可以是小儿高级别胶质瘤（PHGG），例如弥漫性内生性桥脑胶质瘤（DIPG），和/或H3.3突变胶质瘤（例如H3K27M突变胶质瘤）。本公开进一步提供了包括ERK5抑制剂的药物组合物和试剂盒。