tert-butyl 4-(3-hydroxyphenyl)piperidine-1-carboxylate | 940305-06-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(3-hydroxyphenyl)piperidine-1-carboxylate
• CAS: 940305-06-6
• 化学式: C₁₆H₂₃NO₃
• 分子量: 277.364
• InChiKey: JPPUHXYDIMKBOL-UHFFFAOYSA-N

物化性质

• 沸点：
  406.3±45.0 °C(Predicted)
• 密度：
  1.121±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-hydroxyphenyl)piperidine-1-carboxylate 在 四(三苯基膦)钯 、 potassium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 4-[3-(2,4-dichlorophenyl)phenyl]piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Integrating Fragment Assembly and Biophysical Methods in the Chemical Advancement of Small-Molecule Antagonists of IL-2:  An Approach for Inhibiting Protein−Protein Interactions

  摘要：

  Fragment assembly has shown promise for discovering small-molecule antagonists for difficult targets, including protein-protein interactions. Here, we describe a process for identifying a 60 nM inhibitor of the interleukin-2 (IL-2)/IL-2 receptor (IL-2Ralpha) interaction. By use of fragment-based approaches, a compound with millimolar affinity was evolved to a hit series with low micromolar activity, and these compounds were optimized into a lead series with nanomolar affinity. Fragment assembly was useful not only for hit identification, but also for lead optimization. Throughout the discovery process, biophysical methods and structural biology demonstrated that compounds bound reversibly to IL-2 at the IL-2 receptor binding site.

  DOI：

  10.1021/jm049967u
• 作为产物：
  描述：

  tert-butyl 4-(3-hydroxyphenyl)-3,6-dihydro-2H-pyridine-1-carboxylate 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 30.0 ℃ 、275.8 kPa 条件下， 反应 4.0h， 生成 tert-butyl 4-(3-hydroxyphenyl)piperidine-1-carboxylate
  参考文献：
  名称：

  CEREBLON LIGANDS AND BIFUNCTIONAL COMPOUNDS COMPRISING THE SAME

  摘要：

  该描述涉及cereblon E3连接酶结合化合物，包括包含相同成分的双功能化合物，这些化合物作为靶向泛素化的调节剂具有实用价值，尤其是抑制剂，可降解和/或以其他方式抑制根据本公开的双功能化合物。特别是，该描述提供了化合物，其一端含有与cereblon E3泛素连接酶结合的配体，另一端含有与目标蛋白结合的部分，使目标蛋白位于泛素连接酶附近以降解（和抑制）该蛋白。可以合成表现出广泛药理活性的化合物，与几乎所有类型的靶向多肽的降解/抑制一致。

  公开号：

  US20180215731A1

文献信息

• [EN] PIPERIDINE COMPOUNDS HAVING MULTIMODAL ACTIVITY AGAINST PAIN<br/>[FR] COMPOSÉS PIPÉRIDINE À ACTIVITÉ MULTIMODALE CONTRE LA DOULEUR
  申请人：ESTEVE LABOR DR

  公开号：WO2015091988A1

  公开（公告）日：2015-06-25

  The present invention relates to compounds having dual pharmacological activity towards both the sigma (σ) receptor, and the μ-opiod receptor and more particularly to piperidene compounds having this pharmacological activity, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use in therapy, in particular for the treatment of pain.

  本发明涉及具有对σ受体和μ-阿片受体具有双重药理活性的化合物，更具体地涉及具有这种药理活性的哌啶化合物，以及制备这类化合物的方法、包含它们的药物组合物，以及它们在治疗中的使用，特别是用于疼痛治疗。
• Design, Synthesis, and Pharmacological Characterization of Heterobivalent Ligands for the Putative 5-HT_2A/mGlu₂ Receptor Complex
  作者：Christian B. M. Poulie、Na Liu、Anders A. Jensen、Lennart Bunch

  DOI：10.1021/acs.jmedchem.0c01058

  日期：2020.9.10

  We report the synthesis of the first series of heterobivalent ligands targeting the putative heteromeric 5-HT2A/mGlu2 receptor complex, based on the 5-HT2A antagonist MDL-100,907 and the mGlu2 ago-PAM JNJ-42491293. The functional properties of monovalent and heterobivalent ligands were characterized in 5-HT2A-, mGlu2/Gqo5-, 5-HT2A/mGlu2-, and 5-HT2A/mGlu2/Gqo5-expressing HEK293 cells using a Ca2+ imaging

  我们报告了针对5-HT 2A拮抗剂MDL-100,907和mGlu 2 ago-PAM JNJ-42491293的推定异聚5 -HT 2A / mGlu 2受体复合物的第一系列异二价配体的合成。使用Ca 2在表达5-HT 2A-，mGlu 2 / Gqo5-，5-HT 2A / mGlu 2-和5-HT 2A / mGlu 2 / Gqo5的HEK293细胞中表征一价和异二价配体的功能特性。+成像分析和[ 3H]酮色林结合测定。在5-HT 2A / mGlu 2和5-HT 2A / mGlu 2 / Gqo5细胞中的两个受体之间观察到明显的功能性串扰。虽然合成的一价配体保留了5-HT 2A拮抗剂和mGlu 2 ago-PAM的功能，但七个二价配体抑制了5-HT 2A / mGlu 2细胞中5-HT诱导的应答以及5-HT和Glu诱导的应答5-HT 2A / mGlu 2中的响应/ Gqo5细
• ARYL GPR119 AGONISTS AND USES THEREOF
  申请人：Song Jiangao

  公开号：US20120184572A1

  公开（公告）日：2012-07-19

  Aryl GPR119 agonists are provided. These compounds are useful for the treatment of diabetic diseases, including Type II diabetes and other diseases associated with poor glycemic control.

  提供了芳基GPR119激动剂。这些化合物对于治疗糖尿病等疾病非常有用，包括II型糖尿病和其他与血糖控制不佳有关的疾病。
• [EN] GLP-1 RECEPTOR AGONIST AND USE THEREOF<br/>[FR] AGONISTE DU RÉCEPTEUR GLP-1 ET SON UTILISATION
  申请人：ILDONG PHARMACEUTICAL CO LTD

  公开号：WO2021096304A1

  公开（公告）日：2021-05-20

  Disclosed are novel compounds of Chemical Formula 1, optical isomers of the compounds, and pharmaceutically acceptable salts of the compounds or the optical isomers. The compounds, isomers, and salts exhibit excellent activity as GLP-1 receptor agonists. In particular, they, as GLP-1 receptor agonists, exhibit excellent glucose tolerance, thus having a great potential to be used as therapeutic agents for metabolic diseases. Moreover, they exhibit excellent pharmacological safety for cardiovascular systems.

  披露了化学式1的新化合物，这些化合物的光学异构体，以及这些化合物或光学异构体的药用盐。这些化合物、异构体和盐作为GLP-1受体激动剂表现出优异的活性。特别是作为GLP-1受体激动剂，它们表现出优异的葡萄糖耐量，因此具有作为代谢性疾病治疗药物的巨大潜力。此外，它们对心血管系统表现出卓越的药理安全性。
• FUSED HETEROCYCLIC COMPOUND
  申请人：Ishikawa Tomoyasu

  公开号：US20100216788A1

  公开（公告）日：2010-08-26

  The present invention provides a compound represented by the formula: wherein R 1a is a hydrogen atom, R 2a is a C 1-6 alkyl group substituted by a group represented by —NR 6a —CO—(CH 2 ) n —SO 2 — optionally halogenated C 1-4 alkyl wherein n is an integer of 1 to 4, R 6a is a hydrogen atom or a C 1-4 alkyl group, and —(CH 2 ) n — is optionally substituted by C 1-4 alkyl, R 3a is a hydrogen atom or a C 1-6 alkyl group, R 4a is a halogen atom or a C 1-6 alkyl group, R 5a is a halogen atom or a C 1-6 alkyl group, and X a is a hydrogen atom or a halogen atom, or a salt thereof. The compound of the present invention has a superior tyrosine kinase inhibitory action, is highly safe, and is sufficiently satisfactory as a pharmaceutical product.

  本发明提供了一种化合物，其表示为以下式子：其中，R1a是氢原子，R2a是一个C1-6烷基，被一个表示为—NR6a—CO—（CH2）n—SO2—的基团取代，该基团可选地卤代C1-4烷基，其中n是1至4的整数，R6a是氢原子或C1-4烷基，—（ ）n—可选地被C1-4烷基取代，R3a是氢原子或C1-6烷基，R4a是卤原子或C1-6烷基，R5a是卤原子或C1-6烷基，Xa是氢原子或卤原子，或其盐。本发明的化合物具有卓越的酪氨酸激酶抑制作用，高度安全，并且作为药物产品完全令人满意。