4-morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid ter-tbutyl ester | 217807-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 4-morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid ter-tbutyl ester
• 英文别名: N-tert-butoxycarbonyl-4-morpholino-1,2,5,6-tetrahydropyridine；tert-butyl 4-morpholino-5,6-dihydropyridine-1(2H)-carboxylate；4-Morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester；4-morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyI ester；1-t-butoxycarbonyl-4-morpholin-4-yl-1,2,5,6-tetrahydropyridine；tert-butyl-4-morpholino-5,6-dihydropyridine-1(2H)-carboxylate；tert-butyl 4-morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylate
• CAS: 217807-98-2
• 化学式: C₁₄H₂₄N₂O₃
• 分子量: 268.356
• InChiKey: FUJINOGXJWFFFI-UHFFFAOYSA-N

物化性质

• 沸点：
  386.6±42.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid ter-tbutyl ester 在 sodium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 28.0h， 生成 3-(4-chloro-3-iodo-phenyl)-1-(2-cyano-ethyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S

  摘要：

  描述了与碳相连的四氢吡唑吡啶化合物，这些化合物可作为cathepsin S调节剂。这些化合物可用于制备药物组合物和治疗疾病状态、疾病和病况的方法，这些疾病状态、疾病和病况是由cathepsin S活性介导的，如银屑病、疼痛、多发性硬化症、动脉粥样硬化和类风湿性关节炎。

  公开号：

  US20080200454A1
• 作为产物：
  描述：

  4-氧代哌啶酮盐酸盐 在 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 反应 6.0h， 生成 4-morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid ter-tbutyl ester
  参考文献：
  名称：

  N ‐methyl‐3‐(1‐hydroxy‐5‐[ ¹²³ I]iodopent‐4‐enyl)‐4‐acetoxypiperidine, a novel candidate of acetylcholinesterase activity imaging agent

  摘要：

  A novel acetylcholine radioanalog, N-methyl-3-(1-hydroxy-5-[I-123]iodopent-4-enyl)-4-acetoxypiperidine, was prepared by radioiodination of the corresponding tributylstannyl precursor that was synthesized in eight steps from 4-piperidone. The tracer has three asymmetric carbons giving eight optical isomers. Two optical isomers were isolated in the precursor synthesis by diastereomeric and enantiomeric separation. In the incubation experiments using rat cerebral cortical homogenate, one optical isomer was hydrolyzed by acetylcholinesterase with high reactivity and selectivity. The tracer is a candidate for mapping cerebral regional acetylcholinesterase activity by single photon emission computed tomography.

  DOI：

  10.1002/1099-1344(200007)43:8<753::aid-jlcr359>3.0.co;2-#
• 作为试剂：
  描述：

  N-叔丁氧羰基-4-哌啶酮 、 吗啉 、 对甲苯磺酸 、 在 oil 、 4-morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid ter-tbutyl ester 、 吗啉 、 水 作用下， 以 甲苯 为溶剂， 反应 20.0h， 生成 4-morpholin-4-yl-3,6-dihydro-2H-pyridine-1-carboxylic acid ter-tbutyl ester
  参考文献：
  名称：

  SUBSTITUTED 3-AMINO-1-OXO OR THIOXO-1,2,5,6,7,8-HEXAHYDRO-2,7-NAPHTHYRIDINE-4-CARBONITRILES ARE SELECTIVE ALPHA 2B ANTAGONISTS

  摘要：

  本发明提供的化合物是α2B肾上腺素能受体亚型选择性拮抗剂，对其他α肾上腺素能受体没有或仅有微弱的拮抗活性。这些化合物可用作工具化合物，特别是用作开发治疗慢性疼痛、内脏疼痛、角膜疼痛、神经病理性疼痛、青光眼、缺血性神经病和其他神经退行性疾病和病况的化合物的工具化合物。这些化合物还可用作治疗心肌梗死和预防急性冠状动脉事件的化合物。本发明的化合物是3-氨基-1-硫代或氧代-1,2,5,6,7,8-六氢-2,7-萘啶-4-碳腈或其取代衍生物。

  公开号：

  US20100076194A1

文献信息

• N-acylamino acid amide compounds and intermediates for preparation thereof
  申请人：Ube Industries, Ltd.

  公开号：US06265418B1

  公开（公告）日：2001-07-24

  The present invention discloses the compound represented by the formula (I): wherein A represents the following formula (a-1) or the following formula (a-2): B represents the following formula (b): (wherein the symbols are each as defined in the specification) or a pharmaceutically acceptable salts thereof, and intermediates for the preparation thereof, which have excellent platelet aggregation inhibitory activity and other properties and useful as prophylactic or therapeutic agents for diseases associated with a fibrinogen receptor, thrombosis, infarction and the like.

  本发明公开了以下公式（I）所表示的化合物： 其中A代表以下公式（a-1）或以下公式（a-2）： B代表以下公式（b）： （其中符号如规范中所定义）或其药学上可接受的盐，以及用于制备其的中间体，具有优异的血小板聚集抑制活性和其他性质，并且可用作与纤维蛋白原受体、血栓形成、梗塞等疾病相关的预防或治疗剂。
• [EN] MODULATORS OF AMYLOID BETA.<br/>[FR] MODULATEURS DE LA PROTÉINE ?-AMYLOÏDE
  申请人：ASTRAZENECA AB

  公开号：WO2010053438A1

  公开（公告）日：2010-05-14

  The present invention relates to novel compounds of formula I and therapeutically acceptable salts thereof, their pharmaceutical compositions, processes for making them and their use as therapeutic methods for treatment and/or prevention of various diseases. In particular the invention relates to compounds, which inhibit the Aβ40 and Aβ42 production, increase the Aβ37 and Aβ38 production and maintain the Notch signaling and will be used for treatment and/or prevention of Aβ-related pathologies such as Alzheimer's disease, Downs syndrome and β-amyloid angiopathy, such as but not limited to cerebral amyloid angiopathy, hereditary cerebral hemorrhage, disorders associated with cognitive impairment, such as but not limited to MCI ("mild cognitive impairment"), Alzheimer's disease, memory loss, attention deficit symptoms associated with Alzheimer's disease, neurodegeneration associated with diseases such as Alzheimer's disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.

  本发明涉及式I的新化合物及其治疗上可接受的盐，它们的药物组合物，制造它们的方法以及它们作为治疗和/或预防各种疾病的治疗方法的使用。特别是，本发明涉及抑制Aβ40和Aβ42产生，增加Aβ37和Aβ38产生并维持Notch信号传导的化合物，并将用于治疗和/或预防与Aβ相关的病理，如阿尔茨海默病、唐氏综合症和β-淀粉样蛋白血管病，例如但不限于脑淀粉样血管病、遗传性脑出血、与认知障碍相关的疾病，例如但不限于MCI（“轻度认知障碍”）、阿尔茨海默病、记忆丧失、与阿尔茨海默病相关的注意力缺陷症状、与阿尔茨海默病或包括混合血管和退行性来源的痴呆在内的疾病相关的神经退行性变、早老性痴呆、老年性痴呆和与帕金森病、进行性核上瘫或皮层基底退行性变相关的痴呆。
• HETEROBICYCLIC COMPOUNDS USEFUL AS KINASE INHIBITORS
  申请人：Dhar T.G. Murali

  公开号：US20080275052A1

  公开（公告）日：2008-11-06

  A compound of Formula (I) and enantiomers, diastereomers and pharmaceutically-acceptable salts thereof. Also disclosed are pharmaceutical compositions containing compounds of Formula I, and methods of treating conditions associated with the activity of p38 kinase.

  一种由化合物（I）及其对映体、非对映体异构体和药用可接受的盐组成的复合物。还公开了含有化合物（I）的药物组合物，以及治疗与p38激酶活性相关疾病的方法。
• [EN] FUSED PYRAZOLE DERIVATIVES AS NOVEL ERK INHIBITORS<br/>[FR] DÉRIVÉS CONDENSÉS DE PYRAZOLE UTILISÉS COMME NOUVEAUX INHIBITEURS ERK
  申请人：SCHERING CORP

  公开号：WO2012036997A1

  公开（公告）日：2012-03-22

  Disclosed are the ERK inhibitors of Formula (I): (Formula (I)) and the pharmaceutically acceptable salts thereof. All substitutents are as defined herein. Also disclosed are methods of treating cancer using the compounds of Formula (I).

  公开了化学式（I）的ERK抑制剂：（化学式（I））及其药学上可接受的盐。所有取代基如本文所定义。还公开了使用化合物（I）治疗癌症的方法。
• [EN] PROCESSES FOR THE PREPARATION OF CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S<br/>[FR] PROCÉDÉS POUR LA PRÉPARATION DE MODULATEURS CONSTITUÉS DE CATHEPSINE S DE TÉTRAHYDRO-PYRAZOLO-PYRIDINE À LIAISON CARBONE
  申请人：SUNESIS PHARMACEUTICALS INC

  公开号：WO2009102937A1

  公开（公告）日：2009-08-20

  Method of making carbon-linked tetrahydro-pyrazolo-pyridine compounds of the following Formula (I) and pharmaceutically acceptable salts thereof: comprising reacting a compound of formula (IX) with a compound of formula (X) to form a compound of Formula (I); wherein: R1 and R2 taken together with the nitrogen to which they are attached form a morpholine ring, unsubstituted or substituted with one or two methyl substituents; R3 is H or OH; R4 is -SO2CH3, -CONH2, or -COCONH2; R5 is H or methyl; R6 is a benzyl group, unsubstituted or substituted with one or two substituents independently selected from the group consisting of C1-4alkyl, CF3, halo, OH, -OC1-4alkyl, -OCF3, -OCHF2, NRddRee, -CO2C1-4alkyl, -SC1-4alkyl, and -SO2C1-4alkyl; where Rdd and Ree are each independently H or C1-4alkyl; R7 is H, fluoro, or chloro; and LG1 is iodide, bromide, or trifluoromethanesulfonate. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by cathepsin S activity, such as psoriasis, pain, multiple sclerosis, atherosclerosis, and rheumatoid arthritis.

  制备以下化合物Formula (I)及其药用可接受盐的碳连接四氢吡唑吡啶化合物的方法：将Formula (IX)的化合物与Formula (X)的化合物反应以形成Formula (I)的化合物；其中：R1和R2与它们连接的氮一起形成吗啉环，未取代或取代为一个或两个甲基取代基；R3为H或OH；R4为-SO2CH3，-CONH2或-COCONH2；R5为H或甲基；R6为苄基，未取代或取代为一个或两个从C1-4烷基，CF3，卤素，OH，-OC1-4烷基，-OCF3，-OCHF2，NRddRee，-CO2C1-4烷基，-SC1-4烷基和-SO2C1-4烷基组成的取代基中独立选择的取代基；其中Rdd和Ree各自独立为H或C1-4烷基；R7为H，氟或氯；LG1为碘化物，溴化物或三氟甲磺酸盐。这些化合物可用于药物组合物和治疗由S蛋白酶活性介导的疾病状态、紊乱和病况的方法，如牛皮癣、疼痛、多发性硬化症、动脉粥样硬化和类风湿性关节炎。