[1-(6-氯吡嗪-3-基)哌啶-4-基]甲醇 | 1094223-48-9

• 物质功能分类: 医药中间体 - 哒嗪类化合物
• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: [1-(6-氯吡嗪-3-基)哌啶-4-基]甲醇
• 中文别名: [1-(6-氯哒嗪-3-基)哌啶-4-基]甲醇；[1-(6-氯-3-哒嗪基)-4-哌啶基]甲醇
• 英文名称: (1-(6-chloropyridazin-3-yl)piperidin-4-yl)methanol
• 英文别名: [1-(6-chloropyridazin-3-yl)piperidin-4-yl]methanol
• CAS: 1094223-48-9
• 化学式: C₁₀H₁₄ClN₃O
• 分子量: 227.694
• InChiKey: PTLASJDXVKFBFX-UHFFFAOYSA-N

物化性质

• 沸点：
  455.7±30.0 °C(Predicted)
• 密度：
  1.274±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  49.2
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  [1-(6-氯吡嗪-3-基)哌啶-4-基]甲醇 在 Oxone 、 tris-(dibenzylideneacetone)dipalladium(0) 、 三乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 sodium t-butanolate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 9-((1r,4r)-4-methylcyclohexyl)-N-(6-(4-((methylsulfonyl)methyl)-piperidin-1-yl)pyridazin-3-yl)-9H-pyrido[4′,3′:4,5]pyrrolo[2,3-d]pyrimidin-2-amine
  参考文献：
  名称：

  Discovery of AMG 925, a FLT3 and CDK4 Dual Kinase Inhibitor with Preferential Affinity for the Activated State of FLT3

  摘要：

  We describe the structural optimization of a lead compound 1 that exhibits dual inhibitory activities against FLT3 and CDK4. A series of pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidine derivatives was synthesized, and SAR analysis, using cell-based assays, led to the discovery of 28 (AMG 925), a potent and orally bioavailable dual inhibitor of CDK4 and FLT3, including many FLT3 mutants reported to date. Compound 28 inhibits the proliferation of a panel of human tumor cell lines including Colo205 (Rb+) and U937 (FLT3(WT)) and induced cell death in MOLM13 (FLT3(ITD)) and even in MOLM13 (FLT3(ITD, D835Y), which exhibits resistance to a number of FLT3 inhibitors currently under clinical development. At well-tolerated doses, compound 28 leads to significant growth inhibition of MOLM13 xenografts in nude mice, and the activity correlates with inhibition of STAT5 and Rb phosphorylation.

  DOI：

  10.1021/jm500118j
• 作为产物：
  描述：

  4-哌啶甲醇 、 3,6-二氯哒嗪 在 N,N-二异丙基乙胺 作用下， 反应 2.0h， 以98%的产率得到[1-(6-氯吡嗪-3-基)哌啶-4-基]甲醇
  参考文献：
  名称：

  Discovery of AMG 925, a FLT3 and CDK4 Dual Kinase Inhibitor with Preferential Affinity for the Activated State of FLT3

  摘要：

  We describe the structural optimization of a lead compound 1 that exhibits dual inhibitory activities against FLT3 and CDK4. A series of pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidine derivatives was synthesized, and SAR analysis, using cell-based assays, led to the discovery of 28 (AMG 925), a potent and orally bioavailable dual inhibitor of CDK4 and FLT3, including many FLT3 mutants reported to date. Compound 28 inhibits the proliferation of a panel of human tumor cell lines including Colo205 (Rb+) and U937 (FLT3(WT)) and induced cell death in MOLM13 (FLT3(ITD)) and even in MOLM13 (FLT3(ITD, D835Y), which exhibits resistance to a number of FLT3 inhibitors currently under clinical development. At well-tolerated doses, compound 28 leads to significant growth inhibition of MOLM13 xenografts in nude mice, and the activity correlates with inhibition of STAT5 and Rb phosphorylation.

  DOI：

  10.1021/jm500118j

文献信息

• Antipicornaviral pyridazinamines
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0435381A1

  公开（公告）日：1991-07-03

  Piperidinyl, pyrrolidinyl, azepinyl and piperazinyl pyridazines of formula wherein X represents CH or N; R¹ represents hydrogen, C₁₋₄alkyl, halo, hydroxy, trifluoromethyl, cyano, C₁₋₄alkyloxy, C₁₋₄alkylthio, C₁₋₄alkylsulfinyl, C₁₋₄alkylsulfonyl, C₁₋₄alkyloxycarbonyl, C₁₋₄alkylcarbonyl or aryl; R² and R³ represent hydrogen or C₁₋₄alkyl; Alk represents C₁₋₄alkanediyl; R⁴ and R⁵ represent hydrogen, C₁₋₄alkyl or halo; and Het represents the addition salts and stereochemically isomeric forms thereof, said compounds having antipicornaviral activity. Pharmaceutical compositions containing these compounds as active ingredient, and methods of preparing said compounds and pharmaceutical compositions.

  式中的哌啶基、吡咯烷基、氮杂环哌啶基和哌嗪基哒嗪化合物 其中 X 代表 CH 或 NR¹ 代表氢、C₁₋₄烷基、卤代、羟基、三氟甲基、氰基、C₁₋₄烷氧基、C₁₋₄烷硫基、C₁₋₄烷磺基、C₁₋₄烷氧基羰基、C₁₋₄烷羰基或芳基；R² 和 R³ 代表氢或 C₁₋₄ 烷基；烷基代表 C₁₋₄ 烷二基； R⁴ 和 R⁵ 代表氢、C₁₋₄烷基或卤素；以及 Het 代表 其加成盐和立体异构体，所述化合物具有抗逆转录病毒活性。含有这些化合物作为活性成分的药物组合物，以及制备所述化合物和药物组合物的方法。
• US5100893A
  申请人：——

  公开号：US5100893A

  公开（公告）日：1992-03-31
• US5196535A
  申请人：——

  公开号：US5196535A

  公开（公告）日：1993-03-23