叔丁基2,9-二氮杂螺[5.5]十一烷-2-甲酸酯盐酸盐 | 1023301-88-3

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 中文名称: 叔丁基2,9-二氮杂螺[5.5]十一烷-2-甲酸酯盐酸盐
• 英文名称: tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride
• 英文别名: tert-butyl 2,9-diazaspiro[5.5]undecane-2-carboxylate hydrochloride；Tert-butyl 2,9-diazaspiro[5.5]undecane-2-carboxylate hydrochloride；tert-butyl 2,9-diazaspiro[5.5]undecane-2-carboxylate;hydrochloride
• CAS: 1023301-88-3
• 化学式: C₁₄H₂₆N₂O₂*ClH
• 分子量: 290.834
• InChiKey: CRHPGRDEEKJUJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.81
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  41.6
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  叔丁基2,9-二氮杂螺[5.5]十一烷-2-甲酸酯盐酸盐 在 盐酸 、 三乙胺 、 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 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 38.0h， 生成 1-isobutyl-3-[2-[4-[3-[4-[[4-methyl-1-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]indol-3-yl]methyl]phenoxy]propyl]-4,9-diazaspiro[5.5]undecan-9-yl]-2-oxoethyl]urea
  参考文献：
  名称：

  NOVEL UREA COMPOUNDS

  摘要：

  本发明提供了一种化合物I的化学式，或其药用可接受的盐。

  公开号：

  US20150126469A1

文献信息

• [EN] SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1<br/>[FR] PYRIDINES SUBSTITUÉES EN TANT QU'INHIBITEURS DE DNMT1
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2017216726A1

  公开（公告）日：2017-12-21

  The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): (Iar) wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  该发明涉及取代吡啶衍生物。具体而言，该发明涉及符合以下式（Iar）的化合物：（Iar）其中Yar、X1ar、X2ar、R1ar、R2ar、R3ar、R4ar和R5ar如本文所定义；或其药学上可接受的盐或前药。该发明的化合物是DNMT1的选择性抑制剂，可用于治疗癌症、癌前综合征、β血红蛋白病、镰状细胞病、镰状细胞贫血、β地中海贫血以及与DNMT1抑制相关的疾病。因此，该发明进一步涉及包含该发明化合物的药物组合物。该发明还进一步涉及使用该发明化合物或包含该发明化合物的药物组合物抑制DNMT1活性和治疗相关疾病的方法。
• 6-CYCLOAMINO-3-(1H-PYRROLO[2,3-b]PYRIDIN-4-YL)IMIDAZO[1,2-b]PYRIDAZINE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
  申请人：Pacaud Christophe

  公开号：US20120010208A1

  公开（公告）日：2012-01-12

  The invention relates to 6-cycloamino-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazine derivatives corresponding to the general formula (I) in which R 2 represents an aryl group optionally substituted with one or more halogen atoms or C 1-6 -alkyl, C 1-6 -alkyloxy, C 1-6 -alkylthio, C 1-6 -fluoroalkyl, C 1-6 -fluoroalkyloxy and —CN groups or R 2 represents a group chosen from C 1-6 -alkyl, C 1-6 -fluoroalkyl, C 3-7 -cycloalkyl or C 3-7 -cycloalkyl-C 1-6 -alkyl groups; A represents a C 1-7 -alkylene group; B represents a C 1-7 -alkylene group; L represents either a nitrogen atom optionally substituted with an R c or R d group, or a carbon atom substituted with an R e1 group and an R d group or two R e2 groups; the carbon atoms of A and of B being optionally substituted with one or more R f groups, which may be identical to or different from one another. Preparation process and therapeutic use.

  该发明涉及与一般式（I）相对应的6-环氨基-3-(1H-吡咯并[2,3-b]吡啶-4-基)咪唑并[1,2-b]吡啶衍生物，其中R2代表一个芳基，该芳基可选择性地取代一个或多个卤原子或C1-6-烷基、C1-6-烷氧基、C1-6-烷硫基、C1-6-氟烷基、C1-6-氟烷氧基和—CN基，或者R2代表从C1-6-烷基、C1-6-氟烷基、C3-7-环烷基或C3-7-环烷基-C1-6-烷基基团中选择的一种基团；A代表一个C1-7-烷基烯基；B代表一个C1-7-烷基烯基；L代表一个氮原子，该氮原子可选择性地取代为Rc或Rd基团，或者是一个碳原子，该碳原子取代为Re1基团和Rd基团或两个Re2基团；A和B的碳原子可选择性地取代为一个或多个Rf基团，这些基团可以相同也可以不同。制备方法和治疗用途。
• 6-cycloamino-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazine derivatives, preparation thereof and therapeutic use thereof
  申请人：Pacaud Christophe

  公开号：US08546395B2

  公开（公告）日：2013-10-01

  The invention relates to 6-cycloamino-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazine derivatives corresponding to the general formula (I) in which R2 represents an aryl group optionally substituted with one or more halogen atoms or C1-6-alkyl, C1-6-alkyloxy, C1-6-alkylthio, C1-6-fluoroalkyl, C1-6-fluoroalkyloxy and —CN groups or R2 represents a group chosen from C1-6-alkyl, C1-6-fluoroalkyl, C3-7-cycloalkyl or C3-7-cycloalkyl-C1-6-alkyl groups; A represents a C1-7-alkylene group; B represents a C1-7-alkylene group; L represents either a nitrogen atom optionally substituted with an Rc or Rd group, or a carbon atom substituted with an Re1 group and an Rd group or two Re2 groups; the carbon atoms of A and of B being optionally substituted with one or more Rf groups, which may be identical to or different from one another. Preparation process and therapeutic use.

  本发明涉及与通式（I）相对应的6-环氨基-3-(1H-吡咯[2,3-b]吡啶-4-基)咪唑[1,2-b]吡嗪衍生物，其中R2代表芳基基团，其可以选用一个或多个卤原子或C1-6-烷基，C1-6-烷氧基，C1-6-烷硫基，C1-6-氟烷基，C1-6-氟烷氧基和—CN基进行取代，或者R2代表从C1-6-烷基，C1-6-氟烷基，C3-7-环烷基或C3-7-环烷基-C1-6-烷基基团中选择的一个基团；A代表C1-7-烷基链基团；B代表C1-7-烷基链基团；L代表氮原子，其可以选用一个Rc或Rd基团进行取代，或者代表一个用Re1基团和Rd基团或两个Re2基团取代的碳原子；A和B的碳原子可以选用一个或多个Rf基团进行取代，这些基团可以相同或不同。制备方法和治疗用途。
• Substituted pyridines as inhibitors of DNMT1
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：US10975056B2

  公开（公告）日：2021-04-13

  The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代的吡啶衍生物。具体地说，本发明是针对符合式（Iar）的化合物： 其中 Yar、X1ar、X2ar、R1ar、R2ar、R3ar、R4ar 和 R5ar 如本文所定义；或其药学上可接受的盐或原药。 本发明的化合物是 DNMT1 的选择性抑制剂，可用于治疗癌症、癌前综合征、β 血红蛋白病疾病、镰状细胞病、镰状细胞性贫血和β 地中海贫血以及与 DNMT1 抑制相关的疾病。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还进一步涉及使用本发明化合物或包含本发明化合物的药物组合物抑制 DNMT1 活性和治疗与之相关疾病的方法。
• SUBSTITUTED PYRIDINES AS INHIBITORS OF DNMT1
  申请人：GlaxoSmithKline Intellectual Property Development Limited

  公开号：EP3468953A1

  公开（公告）日：2019-04-17