Tert-Butyl 6-(8-(benzo[d]thiazol-2-yl((2-(trimethylsilyl)ethoxy)methyl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-bromopicolinate | 1235036-70-0

• 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: Tert-Butyl 6-(8-(benzo[d]thiazol-2-yl((2-(trimethylsilyl)ethoxy)methyl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-bromopicolinate
• 英文别名: tert-butyl 6-[8-[1,3-benzothiazol-2-yl(2-trimethylsilylethoxymethyl)carbamoyl]-3,4-dihydro-1H-isoquinolin-2-yl]-3-bromopyridine-2-carboxylate
• CAS: 1235036-70-0
• 化学式: C₃₃H₃₉BrN₄O₄SSi
• 分子量: 695.753
• InChiKey: XWQLKUXCWMWSHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.93
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  113
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Tert-Butyl 6-(8-(benzo[d]thiazol-2-yl((2-(trimethylsilyl)ethoxy)methyl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-bromopicolinate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium fluoride 、 偶氮二甲酸二异丙酯 、 [(di(1-adamantyl)butylphosphine)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙腈 为溶剂， 反应 18.0h， 生成 tert-butyl 6-(8-(benzo[d]thiazol-2-yl((2-(trimethylsilyl)ethoxy)methyl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-(3-((8-bromooctyl)oxy)-2-methylphenyl)picolinate
  参考文献：
  名称：

  [EN] TETRAHYDROISOQUINOLINE HETEROBIFUNCTIONAL BCL-XL DEGRADERS
  [FR] AGENTS DE DÉGRADATION DE BCL-XL HÉTÉROBIFONCTIONNELS À BASE DE TÉTRAHYDROISOQUINOLÉINE

  摘要：

  This disclosure provides compounds of Formula (I) or pharmaceutically acceptable salts thereof, that induce degradation of a BCL-XLprotein. These are useful, for example, for treating a cancer in a subject (e.g., a human). This disclosure also provides compositions containing the compounds provided herein as well as methods of using and making the same.

  公开号：

  WO2023215449A1
• 作为产物：
  描述：

  3-溴-6-氯-2-吡啶甲酸 在 吡啶 、 caesium carbonate 、 三乙胺 、 对甲苯磺酰氯 作用下， 以 四氢呋喃 为溶剂， 反应 25.0h， 生成 Tert-Butyl 6-(8-(benzo[d]thiazol-2-yl((2-(trimethylsilyl)ethoxy)methyl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-bromopicolinate 、 (Z)-tert-butyl 3-bromo-6-(8-(3-((2-(trimethylsilyl)ethoxy)methyl)benzo[d]thiazol-2(3H)-ylidenecarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)picolinate
  参考文献：
  名称：

  Structure-Guided Rescaffolding of Selective Antagonists of BCL-X_L

  摘要：

  Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-X-L antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.

  DOI：

  10.1021/ml500030p

文献信息

• HETEROCYCLIC COMPOUNDS AND METHODS OF USE
  申请人：Baell Jonathan Bayldon

  公开号：US20100210622A1

  公开（公告）日：2010-08-19

  In one aspect, the present invention provides for a compound of Formula I in which the variable X 1a , X 1b , X 1c , X 1d , Q, A, R 1 , B, L, E, and the subscripts m and n have the meanings as described herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-x L proteins.

  在一个方面，本发明提供了一种式子为I的化合物，其中变量X1a，X1b，X1c，X1d，Q，A，R1，B，L，E和下标m和n的含义如此处所述。在另一个方面，本发明提供了包含式子I化合物的制药组合物，以及使用式子I化合物治疗由Bcl-2抗凋亡蛋白（例如抗凋亡Bcl-xL蛋白）的表达或过表达所特征的疾病和病状（例如癌症，血小板增多症等）的方法。
• Heterocyclic compounds and methods of use
  申请人：Genentech, Inc.

  公开号：US08232273B2

  公开（公告）日：2012-07-31

  In one aspect, the present invention provides for a compound of Formula I in which the variable X1a, X1b, X1c, X1d, Q, A, R1, B, L, E, and the subscripts m and n have the meanings as described herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-xL proteins.

  在一个方面，本发明提供了一种公式I的化合物，其中变量X1a、X1b、X1c、X1d、Q、A、R1、B、L、E和下标m和n的含义如此处所述。在另一个方面，本发明提供了包含公式I化合物的制药组合物，以及使用公式I化合物治疗表达或过度表达Bcl-2抗凋亡蛋白（例如抗凋亡Bcl-xL蛋白）的疾病和状况（例如癌症、血小板增多症等）的方法。
• Structure-Guided Rescaffolding of Selective Antagonists of BCL-X_L
  作者：Michael F. T. Koehler、Philippe Bergeron、Edna F. Choo、Kevin Lau、Chudi Ndubaku、Danette Dudley、Paul Gibbons、Brad E. Sleebs、Carl S. Rye、George Nikolakopoulos、Chinh Bui、Sanji Kulasegaram、Wilhelmus J. A. Kersten、Brian J. Smith、Peter E. Czabotar、Peter M. Colman、David C. S. Huang、Jonathan B. Baell、Keith G. Watson、Lisa Hasvold、Zhi-Fu Tao、Le Wang、Andrew J. Souers、Steven W. Elmore、John A. Flygare、Wayne J. Fairbrother、Guillaume Lessene

  DOI：10.1021/ml500030p

  日期：2014.6.12

  Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-X-L antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.
• [EN] TETRAHYDROISOQUINOLINE HETEROBIFUNCTIONAL BCL-XL DEGRADERS<br/>[FR] AGENTS DE DÉGRADATION DE BCL-XL HÉTÉROBIFONCTIONNELS À BASE DE TÉTRAHYDROISOQUINOLÉINE
  申请人：[en]TREELINE BIOSCIENCES, INC.

  公开号：WO2023215449A1

  公开（公告）日：2023-11-09

  This disclosure provides compounds of Formula (I) or pharmaceutically acceptable salts thereof, that induce degradation of a BCL-XLprotein. These are useful, for example, for treating a cancer in a subject (e.g., a human). This disclosure also provides compositions containing the compounds provided herein as well as methods of using and making the same.