tert-butyl 4-benzyl-2-(hydroxymethyl)piperazine-1-carboxylate | 936553-15-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-benzyl-2-(hydroxymethyl)piperazine-1-carboxylate
• 英文别名: 4-benzyl-2-(hydroxymethyl)-1-tert-butoxycarbonylpiperazine
• CAS: 936553-15-0
• 化学式: C₁₇H₂₆N₂O₃
• 分子量: 306.405
• InChiKey: YFBKIGOBELWXJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-benzyl-2-(hydroxymethyl)piperazine-1-carboxylate 在 硫酸 、 三溴化硼 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 1,2-二氯乙烷 为溶剂， 反应 27.0h， 生成 2-[2-(Ethoxymethyl)piperazin-1-yl]-6-nitroquinoline
  参考文献：
  名称：

  Syntheses and binding affinities of 6-nitroquipazine analogues for serotonin transporter. Part 5: 2′-Substituted 6-nitroquipazines

  摘要：

  Five C2'-substituted 6-nitroquipazine (6-NQ) derivatives were prepared and evaluated in terms of their biological abilities (K) to displace [3 H]citalopram binding to serotonin transporter. The relationship between their structure and biological activities revealed that shorter alkyl groups tend to possess higher binding affinity. Both compounds 12a and 12c were found to have the equally highest binding affinity (K-i = 0.43 +/- 0.02 nM). (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.001
• 作为产物：
  描述：

  1-Boc-哌嗪-2-羧酸 在 sodium tetrahydroborate 、 calcium(II) chloride dihydrate 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 40.0h， 生成 tert-butyl 4-benzyl-2-(hydroxymethyl)piperazine-1-carboxylate
  参考文献：
  名称：

  新型N-芳基哌嗪CXCR4拮抗剂的发现

  摘要：

  描述了具有取代的哌嗪作为苯并咪唑替代物的一系列新的CXCR4拮抗剂。这些化合物在CXCR4介导的功能和HIV检测中显示出微摩尔至纳摩尔的效价，即在MAGI-CCR5 / CXCR4细胞中抑制X4 HIV-1 IIIB病毒和在Schem- 1细胞中抑制SDF-1诱导的钙释放。SAR的初步研究导致鉴定出一系列N-芳基哌嗪为最有效的化合物。结果表明，SAR表示芳香环的类型和位置，以及接头和立体化学的类型对于活性均很重要。对几种先导化合物进行分析表明，一种（49b）降低了对CYP450和hERG的敏感性，同时考虑了SDF-1和HIV效力（6–20 nM）时获得了最佳的总体特征。

  DOI：

  10.1016/j.bmcl.2015.04.036

文献信息

• [EN] HETEROCYCLIC DERIVATIVES OF PYRAZOL-4-YL-PYRROLO[2,3-D]PYRIMIDINES AS JANUS KINASE INHIBITORS<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES DE PYRAZOL-4-YL-PYRROLO[2,3-D] PYRIMIDINES EN TANT QU'INHIBITEURS DE JANUS KINASE
  申请人：INCYTE CORP

  公开号：WO2011028685A1

  公开（公告）日：2011-03-10

  The present invention provides heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3 djpyrimidines of Formula Ia or a pharmaceutically acceptable salt thereof; wherein: A is H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-I4 cycloalkyl, C2-13 heterocycloalkyl, C6-14 aryl, C1-14 heteroaryl, C3-14 cycloalkyl-C1-4 alkyl, C2-13 heterocycloalkyl-C1-4 alkyl, C6-14 aryl-C1-4 alkyl, or C14 heteroaryl-C14 alkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-14 cycloalkyl, C2-13 heterocycloalkyl, C6-14 aryl, C1-14 heteroaryl, C3-14 cycloalkyl-C1-4 alkyl, C2-13 heterocycloalkyl-C1-4 alkyl, C6-14 aryl-C1-4 alkyl, and C1-14 heteroaryl-C1-4 alkyl are each optionally substituted with I, 2, 3, 4, 5, or 6 independently selected R8 substituents; L is absent, C(=O), C(=O)NH, S(=O), or S(O)2; X is CH or N; Y is H, cyano, halo, C1-4 alkyl, or C1-4 haloalkyl; Z is CR7 or N; R1, R2, and R3 are each independently H, hydroxyl, halo, C1-3 alkyl, or C1-3 haloalkyl; R4 and R5 are each independently H, C1-3 alkyl, or C1-3 haloalkyl; or R4 and R5 together with the carbon atom to which they are attached can form a 3-, 4-, 5-, 6- υr 7-membered cycloalkyl ring; as well as their compositions and methods of use, that modulate the activity of Janus kinases (JAKs) and are useful in the treatment of diseases related to the activity of JAKs including, for example inflammatory disorders, autoimmune disorders, cancer, and other diseases.

  本发明提供了Formula Ia的嘧啶并咪唑-4-基-吡咯[2,3-d]嘧啶的杂环衍生物或其药学上可接受的盐；其中：A为H、C1-6烷基、C2-6烯基、C2-6炔基、C3-I4环烷基、C2-13杂环烷基、C6-14芳基、C1-14杂芳基、C3-14环烷基-C1-4烷基、C2-13杂环烷基-C1-4烷基、C6-14芳基-C1-4烷基或C14杂芳基-C14烷基，其中所述的C1-6烷基、C2-6烯基、C2-6炔基、C3-14环烷基、C2-13杂环烷基、C6-14芳基、C1-14杂芳基、C3-14环烷基-C1-4烷基、C2-13杂环烷基-C1-4烷基、C6-14芳基-C1-4烷基和C1-14杂芳基-C1-4烷基中的每一个可以选择地取代为1、2、3、4、5或6个独立选择的R8取代基；L为空、C(=O)、C(=O)NH、S(=O)或S(O)2；X为CH或N；Y为H、氰基、卤素、C1-4烷基或C1-4卤代烷基；Z为CR7或N；R1、R2和R3分别独立地为H、羟基、卤素、C1-3烷基或C1-3卤代烷基；R4和R5分别独立地为H、C1-3烷基或C1-3卤代烷基；或者R4和R5与它们连接的碳原子一起可以形成3、4、5、6或7成员环烷基环；以及它们的组合物和使用方法，调节Janus激酶（JAKs）的活性，并且在治疗与JAKs活性相关的疾病方面具有用处，例如炎症性疾病、自身免疫性疾病、癌症和其他疾病。
• General Procedures for the Lithiation/Trapping of <i>N</i>-Boc Piperazines
  作者：James D. Firth、Peter O’Brien、Leigh Ferris

  DOI：10.1021/acs.joc.7b00913

  日期：2017.7.7

  stage medicinal chemistry studies, a simple, general synthetic approach is required. Here, we report the development of two general and simple procedures for the racemic lithiation/trapping of N-Boc piperazines. Optimum lithiation times were determined using in situ IR spectroscopy, and the previous complicated and diverse literature procedures were simplified. Subsequent trapping with electrophiles

  为了提供用于早期药物化学研究的α-取代的哌嗪，需要一种简单的通用合成方法。在这里，我们报告了N- Boc哌嗪的外消旋锂化/捕获的两种通用和简单程序的开发。使用原位红外光谱确定了最佳锂化时间，并简化了先前复杂多样的文献程序。随后用亲电试剂进行捕集，得到了多种α-官能化的N - Boc哌嗪。研究了远端N-组的范围和局限性。报道了通过锂化/ Negishi偶联的N- Boc哌嗪的选择性α-和β-芳基化。
• HETEROCYCLIC DERIVATIVES OF PYRAZOL-4-YL-PYRROLO[2,3-d]PYRIMIDINES AS JANUS KINASE INHIBITORS
  申请人：Rodgers James D.

  公开号：US20110059951A1

  公开（公告）日：2011-03-10

  The present invention provides heterocyclic derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines, as well as their compositions and methods of use, that modulate the activity of Janus kinases (JAKs) and are useful in the treatment of diseases related to the activity of JAKs including, for example, inflammatory disorders, autoimmune disorders, cancer, and other diseases.

  本发明提供了吡唑-4-基-吡咯[2,3-d]嘧啶的杂环衍生物，以及它们的组合物和使用方法，可以调节Janus激酶（JAKs）的活性，并且在治疗与JAKs活性相关的疾病方面有用，例如炎症性疾病、自身免疫性疾病、癌症和其他疾病。
• Water-soluble activatable molecular probes, intermediates for the synthesis thereof and associated detection methods
  申请人：ECOLE NORMALE SUPERIEURE DE LYON

  公开号：US10179929B2

  公开（公告）日：2019-01-15

  The invention provides probes with formula (I): in which: X1═NH, O, or S; X2═O or S; SE is a labile group, which may be eliminated under the action of a stimulus that may in particular be the presence of an enzyme, a chemical compound, or a physicochemical characteristic of the medium in which the probe is located; A is an aromatic group that, following cleavage of the C(X2)—O bond in aqueous solution, leads to the liberation of a chromophore or a fluorophore, R represents a hydrogen atom or -(L)n-GP, in which n is equal to 0 or 1, L is a linker arm, and GP is a hydrosolubilizing group; as well as their physiologically acceptable salts, solvates, or hydrates. The invention also provides intermediates for the synthesis thereof and detection methods employing them.

  本发明提供了式 (I) 的探针： 其中 X1═NH、O 或 S；X2═O 或 S；SE 为易变基团，在刺激物的作用下可被消除，刺激物尤其可能是酶的存在、化合物或探针所在介质的物理化学特性；R 代表氢原子或-(L)n-GP，其中 n 等于 0 或 1，L 是连接臂，GP 是水溶性基团； 以及它们生理上可接受的盐、溶液或水合物。本发明还提供了用于合成它们的中间体以及使用它们的检测方法。
• Compounds that inhibit MCL-1 protein
  申请人：AMGEN INC.

  公开号：US10300075B2

  公开（公告）日：2019-05-28

  Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

  本文提供了髓细胞白血病 1 蛋白（Mcl-1）抑制剂、其制备方法、相关药物组合物以及使用方法。例如，本文提供了式 I 的化合物、 或其立体异构体；以及其药学上可接受的盐类和含有这些化合物的药物组合物。本文提供的化合物和组合物可用于治疗癌症等疾病或病症。