6-(4-dimethylamino-piperidin-1-yl)-pyridin-2,3-diyl-diamine | 1254163-25-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 6-(4-dimethylamino-piperidin-1-yl)-pyridin-2,3-diyl-diamine
• 英文别名: 6-[4-(Dimethylamino)piperidin-1-yl]pyridine-2,3-diamine
• CAS: 1254163-25-1
• 化学式: C₁₂H₂₁N₅
• mdl: MFCD24907446
• 分子量: 235.332
• InChiKey: ILGUIXPUABKEHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.583
• 拓扑面积：
  71.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(4-dimethylamino-piperidin-1-yl)-pyridin-2,3-diyl-diamine 在 丁二酸酐 、 potassium carbonate 、 苯磺酸 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 生成 [1-(3-dimethylaminomethyl-3H-imidazo[4,5-b]pyridin-5-yl)-piperidin-4-yl]-dimethyl-amine
  参考文献：
  名称：

  Fragment-Based Discovery of 7-Azabenzimidazoles as Potent, Highly Selective, and Orally Active CDK4/6 Inhibitors

  摘要：

  Herein, we describe the discovery of potent and highly selective inhibitors of both CDK4 and CDK6 via structure-guided optimization of a fragment-based screening hit. CDK6 X-ray crystallography and pharmacokinetic data steered efforts in identifying compound 6, which showed >1000-fold selectivity for CDK4 over CDKs 1 and 2 in an enzymatic assay. Furthermore, 6 demonstrated in vivo inhibition of pRb-phosphorylation and oral efficacy in a Jeko-1 mouse xenograft model.

  DOI：

  10.1021/ml200241a
• 作为产物：
  描述：

  2-氨基-3-硝基-6-氯吡啶 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 100.0 ℃ 、344.75 kPa 条件下， 反应 123.0h， 生成 6-(4-dimethylamino-piperidin-1-yl)-pyridin-2,3-diyl-diamine
  参考文献：
  名称：

  Fragment-Based Discovery of 7-Azabenzimidazoles as Potent, Highly Selective, and Orally Active CDK4/6 Inhibitors

  摘要：

  Herein, we describe the discovery of potent and highly selective inhibitors of both CDK4 and CDK6 via structure-guided optimization of a fragment-based screening hit. CDK6 X-ray crystallography and pharmacokinetic data steered efforts in identifying compound 6, which showed >1000-fold selectivity for CDK4 over CDKs 1 and 2 in an enzymatic assay. Furthermore, 6 demonstrated in vivo inhibition of pRb-phosphorylation and oral efficacy in a Jeko-1 mouse xenograft model.

  DOI：

  10.1021/ml200241a

文献信息

• [EN] IMIDAZOLE DERIVATIVES AND THEIR USE AS MODULATORS OF CYCLIN DEPENDENT KINASES<br/>[FR] DÉRIVÉS D'IMIDAZOLE ET LEUR UTILISATION COMME MODULATEURS DES KINASES DÉPENDANTES DES CYCLINES
  申请人：NOVARTIS AG

  公开号：WO2010125402A1

  公开（公告）日：2010-11-04

  The invention provides compounds of the formula (I): and salts, tautomers, solvates and N-oxides thereof; wherein Q is CH or N; X is N, N+-O- or CR3; Y is N, N+-O- or CR3a; R1 and R2 are independently selected from hydrogen and various substituents as defined in the claims; or R1 and R2 together with the atoms to which they are attached, link to form an optionally substituted carbocyclic or heterocyclic aromatic or non-aromatic ring of 4 to 7 members; R3 is selected from hydrogen and various substituents; and R3a is selected from hydrogen and various substituents as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds. The compounds of formula (I) have activity as inhibitors of CDK kinases and are useful in the treatment of inter alia proliferative diseases such as cancers.

  该发明提供了式(I)的化合物及其盐、互变异构体、溶剂合物和N-氧化物；其中Q为CH或N；X为N、N+-O-或CR3；Y为N、N+-O-或CR3a；R1和R2分别选自氢和各种定义中的取代基；或R1和R2与它们连接的原子一起，形成一个可选择地取代的含氢碳环或杂环芳香或非芳香环，成员数为4到7；R3选自氢和各种取代基；R3a选自氢和各种定义中的取代基。还提供了含有式(I)的化合物的药物组合物，制备该化合物的方法以及该化合物的医药用途。式(I)的化合物具有作为CDK激酶抑制剂的活性，并可用于治疗癌症等增殖性疾病。
• IMIDAZOLE DERIVATIVES AND THEIR USE AS MODULATORS OF CYCLIN DEPENDENT KINASES
  申请人：Howard Steven

  公开号：US20120101064A1

  公开（公告）日：2012-04-26

  The invention provides compounds of the formula (I): and salts, tautomers, solvates and N-oxides thereof; wherein Q is CH or N; X is N, N + —O − or CR 3 ; Y is N, N + —O − or CR 3a ; R 1 and R 2 are independently selected from hydrogen and various substituents as defined in the claims; or R 1 and R 2 together with the atoms to which they are attached, link to form an optionally substituted carbocyclic or heterocyclic aromatic or non-aromatic ring of 4 to 7 members; R 3 is selected from hydrogen and various substituents; and R 3a is selected from hydrogen and various substituents as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds. The compounds of formula (I) have activity as inhibitors of CDK kinases and are useful in the treatment of inter alia proliferative diseases such as cancers.

  本发明提供了式（I）的化合物及其盐，互变异构体，溶剂合物和N-氧化物；其中Q为CH或N；X为N，N+—O−或CR3；Y为N，N+—O−或CR3a；R1和R2分别选自氢和定义在权利要求中的各种取代基；或者R1和R2与它们附着的原子一起连接形成一个可选取代的4到7个成员的碳环芳香族或杂环芳香族或非芳香族环；R3选自氢和各种取代基；而R3a选自氢和定义在权利要求中的各种取代基。还提供了含有式（I）化合物的药物组合物，制备化合物的过程以及化合物的医药用途。式（I）化合物具有作为CDK激酶抑制剂的活性，并可用于治疗增殖性疾病，如癌症等。
• Fragment-Based Discovery of 7-Azabenzimidazoles as Potent, Highly Selective, and Orally Active CDK4/6 Inhibitors
  作者：Young Shin Cho、Hayley Angove、Christopher Brain、Christine Hiu-Tung Chen、Hong Cheng、Robert Cheng、Rajiv Chopra、Kristy Chung、Miles Congreve、Claudio Dagostin、Deborah J. Davis、Ruth Feltell、John Giraldes、Steven D. Hiscock、Sunkyu Kim、Steven Kovats、Bharat Lagu、Kim Lewry、Alice Loo、Yipin Lu、Michael Luzzio、Wiesia Maniara、Rachel McMenamin、Paul N. Mortenson、Rajdeep Benning、Marc O'Reilly、David C. Rees、Junqing Shen、Troy Smith、Yaping Wang、Glyn Williams、Alison J.-A. Woolford、Wojciech Wrona、Mei Xu、Fan Yang、Steven Howard

  DOI：10.1021/ml200241a

  日期：2012.6.14

  Herein, we describe the discovery of potent and highly selective inhibitors of both CDK4 and CDK6 via structure-guided optimization of a fragment-based screening hit. CDK6 X-ray crystallography and pharmacokinetic data steered efforts in identifying compound 6, which showed >1000-fold selectivity for CDK4 over CDKs 1 and 2 in an enzymatic assay. Furthermore, 6 demonstrated in vivo inhibition of pRb-phosphorylation and oral efficacy in a Jeko-1 mouse xenograft model.