叔丁基(3R,4R)-1-苄基-4-甲基哌啶-3-基氨基甲酸酯 | 1092578-34-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 叔丁基(3R,4R)-1-苄基-4-甲基哌啶-3-基氨基甲酸酯
• 英文名称: tert-butyl (3R,4R)-1-benzyl-4-methylpiperidin-3-ylcarbamate
• 英文别名: tert-butyl rac-[(3R,4R)-1-benzyl-4-methylpiperidin-3-yl]carbamate；Carbamicacid,N-[(3R,4R)-4-methyl-1-(phenylmethyl)-3-piperidinyl]-,1,1-dimethylethylester,rel-；tert-butyl N-[(3R,4R)-1-benzyl-4-methylpiperidin-3-yl]carbamate
• CAS: 1092578-34-1
• 化学式: C₁₈H₂₈N₂O₂
• 分子量: 304.433
• InChiKey: RTLUVFHYTBTICI-ZBFHGGJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  叔丁基(3R,4R)-1-苄基-4-甲基哌啶-3-基氨基甲酸酯 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 顺式1-苄基-4-甲基-3-甲氨基-哌啶
  参考文献：
  名称：

  Examining the Chirality, Conformation and Selective Kinase Inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550)

  摘要：

  Here, we examine the significance that stereochemistry plays within the clinically relevant Janus kinase 3 (Jak3) inhibitor 1 (CP-690,550). A synthesis of all four enantiopure stereoisomers of the drug was carried out and an examination of each compound revealed that only the enantiopure 3R,4R isomer was capable of blocking Stat5 phosphorylation (Jak3 dependent). Each compound was profiled across a panel of over 350 kinases, which revealed a high level of selectivity for the Jak family kinases for these related compounds. Each stereoisomer retained a degree of binding to Jak3 and Jak2 and the 3R,4S and 3S,4R stereoisomers were further revealed to have binding affinity for selected members of the STE7 and STE20 subfamily of kinases. finally, an appraisal of the minimum energy conformation of each stereoisomer and molecular docking at Jak3 was performed in an effort to better understand each compounds selectivity and potency profiles.

  DOI：

  10.1021/jm801142b
• 作为产物：
  描述：

  (R)-tert-butyl 1-benzyl-4-methyl-1,2,3,6-tetrahydropyridin-3-ylcarbamate 在 platinum(IV) oxide 、 氢气 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以57%的产率得到叔丁基(3R,4R)-1-苄基-4-甲基哌啶-3-基氨基甲酸酯
  参考文献：
  名称：

  Examining the Chirality, Conformation and Selective Kinase Inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550)

  摘要：

  Here, we examine the significance that stereochemistry plays within the clinically relevant Janus kinase 3 (Jak3) inhibitor 1 (CP-690,550). A synthesis of all four enantiopure stereoisomers of the drug was carried out and an examination of each compound revealed that only the enantiopure 3R,4R isomer was capable of blocking Stat5 phosphorylation (Jak3 dependent). Each compound was profiled across a panel of over 350 kinases, which revealed a high level of selectivity for the Jak family kinases for these related compounds. Each stereoisomer retained a degree of binding to Jak3 and Jak2 and the 3R,4S and 3S,4R stereoisomers were further revealed to have binding affinity for selected members of the STE7 and STE20 subfamily of kinases. finally, an appraisal of the minimum energy conformation of each stereoisomer and molecular docking at Jak3 was performed in an effort to better understand each compounds selectivity and potency profiles.

  DOI：

  10.1021/jm801142b

文献信息

• CONDENSED PYRROLOPYRIDINE DERIVATIVE
  申请人：Shirakami Shohei

  公开号：US20120034250A1

  公开（公告）日：2012-02-09

  [Problem] The present invention provides a condensed pyrrolopyridine derivative which is useful as an active ingredient for a pharmaceutical composition, in particular, a pharmaceutical composition for preventing or treating diseases caused by undesirable cytokine signal transduction or diseases caused by abnormal cytokine signal transduction. [Means for Solution] The present inventors have extensively studied a compound having a JAK inhibitory action, and as a result, they have found that a condensed pyrrolopyridine derivative which is the compound of the present invention has an excellent JAK inhibitory action, and is therefore useful as an agent for preventing or treating diseases caused by undesirable cytokine signal transduction or diseases caused by abnormal cytokine signal transduction, thereby completing the present invention.

  本发明提供了一种浓缩的吡咯吡啶衍生物，可用作制药组合物的活性成分，特别是用于预防或治疗由不良细胞因子信号传导或异常细胞因子信号传导引起的疾病的制药组合物。本发明的解决方案是，本发明的发明者广泛研究了一种具有JAK抑制作用的化合物，结果发现，本发明的一种浓缩的吡咯吡啶衍生物具有优异的JAK抑制作用，因此可用作预防或治疗由不良细胞因子信号传导或异常细胞因子信号传导引起的疾病的药剂，从而完成了本发明。
• FUSED PYRROLOPYRIDINE DERIVATIVE
  申请人：Astellas Pharma Inc.

  公开号：EP2420502A1

  公开（公告）日：2012-02-22

  [Problem] The present invention provides a condensed pyrrolopyridine derivative which is useful as an active ingredient for a pharmaceutical composition, in particular, a pharmaceutical composition for preventing or treating diseases caused by undesirable cytokine signal transduction or diseases caused by abnormal cytokine signal transduction. [Means for Solution] The present inventors have extensively studied a compound having a JAK inhibitory action, and as a result, they have found that a condensed pyrrolopyridine derivative which is the compound of the present invention has an excellent JAK inhibitory action, and is therefore useful as an agent for preventing or treating diseases caused by undesirable cytokine signal transduction or diseases caused by abnormal cytokine signal transduction, thereby completing the present invention.

  问题 本发明提供了一种缩合吡咯并吡啶衍生物，该衍生物可作为药物组合物的活性成分，特别是用于预防或治疗由不良细胞因子信号转导引起的疾病或由异常细胞因子信号转导引起的疾病的药物组合物。 [解决方法］ 本发明人广泛研究了具有 JAK 抑制作用的化合物，结果发现本发明化合物的缩合吡咯并吡啶衍生物具有极好的 JAK 抑制作用，因此可用作预防或治疗由不良细胞因子信号转导引起的疾病或由异常细胞因子信号转导引起的疾病的药剂，从而完成了本发明。
• Substituted pyrrolopyridine JAK inhibitors and methods of making and using the same
  申请人：ACLARIS THERAPEUTICS, INC.

  公开号：US10981906B2

  公开（公告）日：2021-04-20

  The present invention relates to new pyrrolopyridine compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibition of JAK1 and JAK3 kinase activity in a human or animal subject are also provided for the treatment diseases such as pruritus, alopecia, androgenetic alopecia, alopecia areata, vitiligo and psoriasis.

  本发明涉及新的吡咯并吡啶化合物和组合物及其作为药物治疗疾病的应用。本发明还提供了抑制人或动物体内 JAK1 和 JAK3 激酶活性的方法，用于治疗瘙痒症、脱发、雄激素性脱发、斑秃、白癜风和银屑病等疾病。
• SUBSTITUTED PYRROLOPYRIDINE JAK INHIBITORS AND METHODS OF MAKING AND USING THE SAME
  申请人：ACLARIS THERAPEUTICS, INC.

  公开号：US20190135808A1

  公开（公告）日：2019-05-09

  The present invention relates to new pyrrolopyridine compounds and compositions and their application as pharmaceuticals for the treatment of disease. Methods of inhibition of JAK1 and JAK3 kinase activity in a human or animal subject are also provided for the treatment diseases such as pruritus, alopecia, androgenetic alopecia, alopecia areata, vitiligo and psoriasis.
• Examining the Chirality, Conformation and Selective Kinase Inhibition of 3-((3<i>R</i>,4<i>R</i>)-4-methyl-3-(methyl(7H-pyrrolo[2,3-<i>d</i>]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550)
  作者：Jian-kang Jiang、Kamran Ghoreschi、Francesca Deflorian、Zhi Chen、Melissa Perreira、Marko Pesu、Jeremy Smith、Dac-Trung Nguyen、Eric H. Liu、William Leister、Stefano Costanzi、John J. O’Shea、Craig J. Thomas

  DOI：10.1021/jm801142b

  日期：2008.12.25

  Here, we examine the significance that stereochemistry plays within the clinically relevant Janus kinase 3 (Jak3) inhibitor 1 (CP-690,550). A synthesis of all four enantiopure stereoisomers of the drug was carried out and an examination of each compound revealed that only the enantiopure 3R,4R isomer was capable of blocking Stat5 phosphorylation (Jak3 dependent). Each compound was profiled across a panel of over 350 kinases, which revealed a high level of selectivity for the Jak family kinases for these related compounds. Each stereoisomer retained a degree of binding to Jak3 and Jak2 and the 3R,4S and 3S,4R stereoisomers were further revealed to have binding affinity for selected members of the STE7 and STE20 subfamily of kinases. finally, an appraisal of the minimum energy conformation of each stereoisomer and molecular docking at Jak3 was performed in an effort to better understand each compounds selectivity and potency profiles.