tert-butyl 4-(2-(dimethoxyphosphoryl)acetyl)piperidine-1-carboxylate

• 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-(2-(dimethoxyphosphoryl)acetyl)piperidine-1-carboxylate
• 英文别名: tert-butyl 4-(2-dimethoxyphosphorylacetyl)piperidine-1-carboxylate
• 化学式: C₁₄H₂₆NO₆P
• 分子量: 335.337
• InChiKey: YMTYODWFOPZEBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(2-(dimethoxyphosphoryl)acetyl)piperidine-1-carboxylate 在 甲醇 、 sodium tetrahydroborate 、 sodium hydride 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.67h， 生成 1-(4-(1-hydroxy-2-(5H-imidazo[5,1-a]isoindol-5-yl)ethyl)piperidin-1-yl)-2-phenylethan-1-one
  参考文献：
  名称：

  Discovery of Clinical Candidate (1R,4r)-4-((R)-2-((S)-6-Fluoro-5H-imidazo[5,1-a]isoindol-5-yl)-1-hydroxyethyl)cyclohexan-1-ol (Navoximod), a Potent and Selective Inhibitor of Indoleamine 2,3-Dioxygenase 1

  摘要：

  A novel class of 5-substituted 5H-imidazo[5,1-a]isoindoles are described as potent inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1). A structure-based drug design approach was used to elaborate the 5H-imidazo[5,1-a]isoindole core and to improve potency and pharmacological properties. Suitably placed hydrophobic and polar functional groups in the lead molecule allowed improvement of IDO1 inhibitory activity while minimizing off-target liabilities. Structure-activity relationship studies focused on optimizing IDO1 inhibition potency and a pharmacokinetic profile amenable to oral dosing while controlling CYP450 and hERG inhibitory properties.

  DOI：

  10.1021/acs.jmedchem.9b00662
• 作为产物：
  描述：

  N-Boc-4-哌啶甲酸甲酯 、 甲基膦酸二甲酯 在 lithium diisopropyl amide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 以96%的产率得到tert-butyl 4-(2-(dimethoxyphosphoryl)acetyl)piperidine-1-carboxylate
  参考文献：
  名称：

  制备β-酮膦酸酯的一般程序

  摘要：

  描述了制备β-酮膦酸酯的温和的高产率方法。对于酯和膦酸酯而言，缩合是普遍的，并且在0℃下在数分钟内以高收率获得产物。该反应程序操作简单并且适于大规模制备。

  DOI：

  10.1021/jo901552k

文献信息

• Fused imidazopyridine derivatives as antihyperlipidemic agents
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06235731B1

  公开（公告）日：2001-05-22

  A novel compound of the formula: wherein ring Q is an optionally substituted pyridine ring; One of R0, R1 and R2 is —Y0—Z0, and the other tow groups are a hydrogen, a halogen, an optionally substituted hydroxy group, a hydrocarbon group that may be an optionally substituted hydrocarbon group or an acyl group; Y0 is a bond or an optionally substituted bivalent hydrocarbon group; Z0 is a basic group which may be bonded via oxygen, nitrogen, —CO—, —CS—, —SO2N(R3)— (where R3 is hydrogen or an optionally substituted hydrocarbon group), or S(O)n (wherein n is to 0, 1 or 2); ......... is a single bond or a double bond, or a salt thereof, which has an excellent LDL receptor up-regulating, blood-lipids lowering, blood-sugar lowering and diabetic complication-ameliorating activity.

  其中环Q是一个可选择取代的吡啶环； R0、R1和R2中的一个是—Y0—Z0，另外两个基团是氢、卤素、可选择取代的羟基、可能是可选择取代的碳氢基团或酰基； Y0是一个键或一个可选择取代的二价碳氢基团； Z0是一种碱性基团，可以通过氧、氮、—CO—、—CS—、—SO2N(R3)—（其中R3是氢或可选择取代的碳氢基团）或S(O)n（其中n为0、1或2）与之键合； .........是一种单键或双键，或其盐，具有出色的LDL受体上调、降低血脂、降低血糖和改善糖尿病并发症的活性。
• A General Procedure for the Preparation of β-Ketophosphonates
  作者：Kevin M. Maloney、John Y. L. Chung

  DOI：10.1021/jo901552k

  日期：2009.10.2

  A mild, high-yielding procedure for the preparation of β-ketophosphonates is described. The condensation is general with respect to the ester and phosphonate, and the products are obtained in high yields within minutes at 0 °C. The reaction procedure is operationally simple and amenable to large-scale preparations.

  描述了制备β-酮膦酸酯的温和的高产率方法。对于酯和膦酸酯而言，缩合是普遍的，并且在0℃下在数分钟内以高收率获得产物。该反应程序操作简单并且适于大规模制备。
• [EN] TRICYCLIC COMPOUNDS AS INHIBITORS OF IMMUNOSUPPRESSION MEDIATED BY TRYPTOPHAN METABOLIZATION<br/>[FR] COMPOSÉS TRICYCLIQUES UTILISÉS EN TANT QU'INHIBITEURS DE L'IMMUNOSUPPRESSION DONT LA MÉDIATION EST ASSURÉE PAR LA MÉTABOLISATION DU TRYPTOPHANE
  申请人：NEWLINK GENETICS CORP

  公开号：WO2014159248A1

  公开（公告）日：2014-10-02

  Presently provided are inhibitors of IDO and TDO and pharmaceutical compositions thereof, useful for modulating an activity of indoleamine 2,3-dioxygenase and tryptophan 2,3 dioxygenase; treating immunosuppression; treating a medical conditions that benefit from the inhibition of tryptophan degradation; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosupression associated with an infectious disease.

  目前提供的是IDO和TDO的抑制剂及其药物组合物，用于调节吲哌啶2,3-二氧化酶和色氨酸2,3-二氧化酶的活性；治疗免疫抑制；治疗受益于色氨酸降解抑制的医疗状况；增强包括给予抗癌剂的抗癌治疗的有效性；治疗与癌症相关的肿瘤特异性免疫抑制；以及治疗与传染病相关的免疫抑制。
• 1-CYCLOALKYL- OR 1-HETEROCYCLYL-HYDROXYIMINO-3-PHENYL-PROPANES
  申请人：Hoffmann-La Roche Inc.

  公开号：US20130109718A1

  公开（公告）日：2013-05-02

  This invention relates to novel 1-cycloalkyl- or 1-heterocyclyl-hydroxyimino-3-phenyl-propanes of the formula wherein R 1 to R 7 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may therefore be useful as medicaments for the treatment of diseases such as type II diabetes.

  这项发明涉及新颖的1-环烷基或1-杂环烷基-羟胺基-3-苯基丙烷的化合物，其结构如下式所示：其中R1至R7如描述和权利要求中所定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，因此可能用作治疗疾病如2型糖尿病的药物。
• [EN] 1-CYCLOALKYL- OR 1-HETEROCYCLYL-HYDROXYIMINO-3-PHENYL-PROPANES<br/>[FR] 1-CYCLOALKYL- OU 1-HÉTÉROCYCLYL-HYDROXYIMINO-3-PHÉNYL-PROPANES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013060653A1

  公开（公告）日：2013-05-02

  This invention relates to novel 1-cycloalkyl- or l-heterocyclyl-hydroxyimino-3-phen propanes of the formula wherein R1 to R7 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are GPBAR1 agonists and may therefore be useful as medicaments for the treatment of diseases such as type II diabetes.

  这项发明涉及新颖的1-环烷基或1-杂环烷基-羟胺基-3-苯基丙烷类化合物的公式，其中R1至R7如描述和索赔中定义，并且其药学上可接受的盐。这些化合物是GPBAR1激动剂，因此可能作为治疗疾病如2型糖尿病的药物而有用。