1-(tert-butoxycarbonyl)-4-(4-cyanophenoxymethyl)piperidine | 176967-61-6

• 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: 1-(tert-butoxycarbonyl)-4-(4-cyanophenoxymethyl)piperidine
• 英文别名: 4-(4-cyanophenoxymethyl)-piperidine-1-carboxylic acid tert-butyl ester；tert-butyl 4-[(4-cyanophenoxy)methyl]piperidine-1-carboxylate
• CAS: 176967-61-6
• 化学式: C₁₈H₂₄N₂O₃
• 分子量: 316.4
• InChiKey: MUTUQAMHTGWPQI-UHFFFAOYSA-N

物化性质

• 沸点：
  456.9±15.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  62.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(tert-butoxycarbonyl)-4-(4-cyanophenoxymethyl)piperidine 在 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 96.0h， 生成 7-[(4-cyanophenoxy)methyl]-4-azoniaspiro[3.5]nonane methanesulfonate
  参考文献：
  名称：

  Utility of azetidinium methanesulfonates for radiosynthesis of 3-[18F]fluoropropyl amines

  摘要：

  观察到 3-甲磺酰氧基丙基叔胺环化形成甲磺酸氮杂环丁烷。利用 3-甲磺酰氧基丙胺的热诱导环化反应制备了氮杂环丁烷甲磺酸盐。研究发现，氮杂环丁烷甲烷磺酸盐能有效地结合放射性[18F]氟化物（衰变校正产率大于 60%），从而高效合成了 3-[18F]fluoropropyl tertiary amines（3-[18F]氟丙基叔胺）。Copyright © 2004 John Wiley & Sons, Ltd. All Rights Reserved.

  DOI：

  10.1002/jlcr.884
• 作为产物：
  描述：

  N-Boc-4-哌啶甲醇 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.17h， 生成 1-(tert-butoxycarbonyl)-4-(4-cyanophenoxymethyl)piperidine
  参考文献：
  名称：

  Synthesis of 1-(trans-[123I]Iodopropen-2-yl)-4-(4-cyanophenoxy-methyl)piperidine: A selective sigma receptor radioligand for SPECT

  摘要：

  1-(trans-[I-123]Iodopropen-2-yl)-4-(4-cyanophenoxymethyl)piperidine has been prepared as a novel sigma receptor ligand for SPECT. This ligand was found to be selective in vitro for the sigma receptor site (Ki(sigma) = 21.7 nM) when tested in a variety of neuroreceptor binding assays. The lipophilicity of this ligand (log P-7.5 = 3.36) is appropriate for good brain uptake and relatively low non-specific binding. Radioiodination was accomplished using classical electrophilic iododestannylation methods and specific activity of the purified product was > 2100 mCi/mu mole. Radiochemical yields were 60-80% EOS and radiochemical purities were > 99%. The average time of synthesis and purification was 35 minutes.

  DOI：

  10.1002/(sici)1099-1344(199603)38:3<215::aid-jlcr834>3.0.co;2-f

文献信息

• Pyrrolopyrimidine A2b selective antagonist compounds, their synthesis and use
  申请人：——

  公开号：US20030229067A1

  公开（公告）日：2003-12-11

  The subject invention provides compounds having the structure: 1 wherein, R 1 is a substituted or unsubstituted alkyl, wherein the substituent is hydroxyl, dihydroxy, carboxyl, —C(═O)NR a R b , —NR a R b , —NR a C(═O)NR a R b , —NR a C(═O)OR a , —OC(═O)NR a R b , or —NHC(═O)R a ; R 2 is hydrogen or a substituted or unsubstituted alkyl, wherein the substituent is hydroxyl, dihydroxy, carboxyl, —C(═O)NR a R b , —NR a R b , —NR a C(═O)NR a R b , —NR a C(═O)OR a , —OC(═O)NR a R b , or —NHC(═O)R a , or R 1 , R 2 and N together form a substituted piperazine, substituted azetidine ring, or a pyrrolidine ring substituted with —(CH 2 ) 2 OH or —CH 2 C(═O)OH; R 3 is a substituted or unsubstituted phenyl or a 5-6 membered heteroaryl ring, wherein the substituent is halogen, hydroxyl, cyano, (C 1 -C 15 )alkyl, (C 1 -C 15 )alkoxy, or —NR a R b ; R 4 is hydrogen or substituted or unsubstituted (C 1 -C 15 )alkyl; R 5 is —(CH 2 ) m OR 6 , —CHNOR 7 , —C(═O)NR 8 R 9 , —(CH 2 ) m C(═O)OR 10 , —(CH 2 ) k C(═O)NR 11 R 12 ; wherein R 6 is a substituted or unsubstituted (C 1 -C 30 )alkyl, (C 3 -C 10 )cycloalkyl, or an aryl, heteroaryl or 4-8 membered heterocyclic ring; R 7 is hydrogen, or a substituted or unsubstituted (C 1 -C 30 )alkyl, (C 1 -C 30 )alkylaryl; R 8 and R 9 are each independently hydrogen, or a substituted or unsubstituted (C 1 -C 30 )alkyl, (C 1 -C 30 )alkylaryl, (C 1 -C 30 )alkylamino, (C 1 -C 30 )alkoxy, or a saturated or unsaturated, monocyclic or bicyclic, carbocyclic or heterocyclic ring, or R 8 , N, and R 9 together form a substituted or unsubstituted 4-8 membered heterocyclic ring; R 10 is hydrogen or a substituted or unsubstituted (C 1 -C 30 )alkyl, (C 3 -C 10 )cycloalkyl, or an aryl, heteroaryl or heterocyclic ring; R 11 , N and R 12 together form a 4-8 membered heterocyclic ring; R a and R b are each independently hydrogen or alkyl; m is 0, 1, 2 or 3; and k is 1, 2 or 3, or a specific enantiomer thereof, or a specific tautomer thereof, or a pharmaceutically acceptable salt thereof, and a method for treating a disease associated with the A 2b adenosine receptor in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of the compounds of the invention.

  该主题发明提供具有以下结构的化合物： 1 其中， R 1 是取代或未取代的烷基，其中取代基是羟基、二羟基、羧基、—C(═O)NR a R b 、—NR a R b 、—NR a C(═O)NR a R b 、—NR a C(═O)OR a 、—OC(═O)NR a R b 或—NHC(═O)R a ； R 2 是氢或取代或未取代的烷基，其中取代基是羟基、二羟基、羧基、—C(═O)NR a R b 、—NR a R b 、—NR a C(═O)NR a R b 、—NR a C(═O)OR a 、—OC(═O)NR a R b 或—NHC(═O)R a ，或 R 1 、R 2 和N共同形成取代哌嗪、取代氮杂环丙烷环或取代的—(CH 2 ) 2 OH或—CH 2 C(═O)OH的吡咯烷环； R 3 是取代或未取代的苯基或5-6成员杂芳环，其中取代基是卤素、羟基、氰基、(C 1 -C 15 )烷基、(C 1 -C 15 )烷氧基或—NR a R b ； R 4 是氢或取代或未取代的(C 1 -C 15 )烷基； R 5 是—(CH 2 ) m OR 6 、—CHNOR 7 、—C(═O)NR 8 R 9 、—(CH 2 ) m C(═O)OR 10 、—(CH 2) k C(═O)NR 11 R 12 ； 其中R 6 是取代或未取代的(C 1 -C 30 )烷基、(C 3 -C 10 )环烷基或芳基、杂芳基或4-8成员杂环环； R 7 是氢或取代或未取代的(C 1 -C 30 )烷基、(C 1 -C 30 )烷基芳基； R 8 和R 9 各自独立地是氢或取代或未取代的(C 1 -C 30 )烷基、(C 1 -C 30 )烷基芳基、(C 1 -C 30 )烷基氨基、(C 1 -C 30 )烷氧基或饱和或不饱和的、单环或双环的、碳环或杂环环，或 R 8 、N和R 9 共同形成取代或未取代的4-8成员杂环环； R 10 是氢或取代或未取代的(C 1 -C 30 )烷基、(C 3 -C 10 )环烷基或芳基、杂芳基或杂环环； R 11 、N和R 12 共同形成4-8成员杂环环； R a 和R b 各自独立地是氢或烷基； m为0、1、2或3；和 k为1、2或3， 或其特定对映体，或其特定互变异构体，或其药学上可接受的盐，以及一种治疗与需要此类治疗的受试者相关的A 2b 腺苷受体相关疾病的方法，包括向受试者施用该发明化合物的治疗有效量。
• [EN] PIPERIDINE-BASED SIGMA RECEPTOR LIGANDS<br/>[FR] LIGANDS DE RECEPTEURS SIGMA A BASE DE PIPERIDINE
  申请人：AUSTRALIAN NUCLEAR SCIENCE & TECHNOLOGY ORGANISATION

  公开号：WO1996020928A1

  公开（公告）日：1996-07-11

  (EN) Compounds of formula (I) or pharmaceutically acceptable salts therof wherein X = O, CO or CHOH; R' is fluoroalkyl of 2 to 5 carbon atoms and 1 to 11 fluorine atoms; mono- and di-substituted benzyl wherein the substituents are selected from NO2, CN, I, Br, F, OH, OCH3 or OCH2OCH3 the substituents being at the meta or para positions; iodoalkenyl groups of 3 to 6 carbon atoms; bromoalkenyl groups of 3 to 6 carbon atoms; alkyl groups of 1 to 5 carbon atoms; or hydroxyalky containing 2 to 5 carbon atoms and 1 to 3 hydroxyl groups; R' is phenyl optionally substituted with one or two groups at the meta or para positions selected from methyl, ethyl, I, Br, CN, NO2, OH, CF3, OR wherein R is phenyl, 4-cyanophenyl, 4-nitrophenyl, CF3, methyl or ethyl; iodoalkenyl of 3 to 6 carbon atoms; bromoalkenyl of 3 to 6 carbon atoms; fluoroalkyl of 1 to 5 carbon atoms and 1 to 11 fluorine atoms; or alkyl groups of 1 to 5 carbon atoms as piperidine based sigma-1 receptor ligands suitable for use in diagnosis and therapy of diseases such as psychosis and cancer.(FR) La présente invention concerne des composés ayant la formule (I) ou des sels de ces composés acceptables sur le plan pharmaceutique, dans laquelle X = O, CO ou CHOH; R' étant un fluoroalkyle de 2 à 5 atomes de carbone et 1 à 11 atomes de fluor; du benzyle mono et bisubstitué, les substituants étant choisis parmi les suivants: NO2, CN, I, Br, F, OH, OCH3 et OCH2OCH3, et se trouvant aux positions méta ou para; des groupes iodoalcényles ayant de 3 à 6 atomes de carbone; des groupes bromoalcényles ayant de 3 à 6 atomes de carbone; des groupes alkyles ayant de 1 à 5 atomes de carbone, ou un hydroxyalkyle comportant de 2 à 5 atomes de carbone et de 1 à 3 groupes hydroxyles; R' est un phényle, avec en variante substitution avec un ou deux groupes aux positions méta ou para, choisis parmi le méthyle, l'éthyle, I, Br, CN, NO2, OH, CF3, OR, R étant phényle, 4-cyanophényle, 4-nitrophényle, CF3, méthyle ou éthyle; un iodoalcényle de 3 à 6 atomes de carbone, un bromoalcényle de 3 à 6 atomes de carbone, un fluoroalkyle de 1 à 5 atomes de carbone et 1 à 11 atomes de fluor, ou des groupes alkyle de 1 à 5 atomes de carbone. Ces composés sont utilisés comme ligands de récepteurs sigma-1 à base de pipéridine, dans le cadre du diagnostic et de la thérapie de maladies telles que les psychoses et le cancer.

  化合物的式子为（I），或其在药学上可接受的盐，其中X = O，CO或CHOH; R'是2至5个碳原子和1至11个氟原子的氟烷基；单取代和双取代苯甲基，其中取代基选择自NO2，CN，I，Br，F，OH，OCH3或OCH2OCH3，取代基位于间位或对位；3至6个碳原子的碘烯基；3至6个碳原子的溴烯基；1至5个碳原子的烷基；或含有2至5个碳原子和1至3个羟基的羟基烷基；R'是苯基，可以在间位或对位处选择一个或两个取代基，所选取代基来自甲基，乙基，I，Br，CN， ，OH，CF3，OR，其中R是苯基，4-氰基苯基，4-硝基苯基， ，甲基或乙基；3至6个碳原子的碘烯基；3至6个碳原子的溴烯基；1至5个碳原子和1至11个氟原子的氟烷基；或1至5个碳原子的烷基。这些化合物作为基于哌啶的sigma-1受体配体，适用于诊断和治疗精神病和癌症等疾病。
• PYRROLOPYRIMIDINE A2B SELECTIVE ANTAGONIST COMPOUNDS, THEIR SYNTHESIS AND USE
  申请人：Castelhano Arlindo

  公开号：US20080261943A1

  公开（公告）日：2008-10-23

  The subject invention provides compounds having the structure: wherein, R 1 is a substituted or unsubstituted alkyl, wherein the substituent is hydroxyl, dihydroxy, carboxyl, —C(═O)NR a R b , —NR a R b , —NR a C(═O)NR a R b , —NR a C(═O)OR a , —OC(═O)NR a R b , or —NH C(═O) R a ; R 2 is hydrogen or a substituted or unsubstituted alkyl, wherein the substituent is hydroxyl, dihydroxy, carboxyl, —C(═O)NR a R b , —NR a R b , —NR a C(═O)NR a R b , —NR a C(═O)OR a , —OC(═O)NR a R b , or —NHC(═O)R a , or R 1 , R 2 and N together form a substituted piperazine, substituted azetidine ring, or a pyrrolidine ring substituted with —(CH 2 ) 2 OH or —CH 2 C(═O)OH; R 3 is a substituted or unsubstituted phenyl or a 5-6 membered heteroaryl ring, wherein the substituent is halogen, hydroxyl, cyano, (C 1 -C 15 )alkyl, (C 1 -C 15 )alkoxy, or —NR a R b ; R 4 is hydrogen or substituted or unsubstituted (C 1 -C 15 )alkyl; R 5 is —(CH 2 ) m OR 6 , —CHNOR 7 , —C(═O)NR 8 R 9 , —(CH 2 ) m C(═O)OR 10 , —(CH 2 ) k C(═O)NR 11 R 12 ; wherein R 6 is a substituted or unsubstituted (C 1 -C 30 )alkyl, (C 3 -C 10 )cycloalkyl, or an aryl, heteroaryl or 4-8 membered heterocyclic ring; R 7 is hydrogen, or a substituted or unsubstituted (C 1 -C 30 )alkyl, (C 1 -C 30 )alkylaryl; R 8 and R 9 are each independently hydrogen, or a substituted or unsubstituted (C 1 -C 30 )alkyl, (C 1 -C 30 )alkylaryl, (C 1 -C 30 )alkylamino, (C 1 -C 30 )alkoxy, or a saturated or unsaturated, monocyclic or bicyclic, carbocyclic or heterocyclic ring, or R 8 , N, and R 9 together form a substituted or unsubstituted 4-8 membered heterocyclic ring; R 10 is hydrogen or a substituted or unsubstituted (C 1 -C 30 )alkyl, (C 3 -C 10 )cycloalkyl, or an aryl, heteroaryl or heterocyclic ring; R 11 , N and R 12 together form a 4-8 membered heterocyclic ring; R a and R b are each independently hydrogen or alkyl; m is 0, 1, 2 or 3; and k is 1, 2 or 3, or a specific enantiomer thereof, or a specific tautomer thereof, or a pharmaceutically acceptable salt thereof, and a method for treating a disease associated with the A 2b adenosine receptor in a subject in need of such treatment comprising administering to the subject a therapeutically effective amount of the compounds of the invention.

  本发明提供了具有以下结构的化合物：其中，R1是取代或未取代的烷基，其中取代基是羟基，二羟基，羧基，—C（═O）NRaRb，—NRaRb，—NRaC（═O）NRaRb，—NRaC（═O）ORa，—OC（═O）NRaRb或—NH C（═O） Ra；R2是氢或取代或未取代的烷基，其中取代基是羟基，二羟基，羧基，—C（═O）NRaRb，—NRaRb，—NRaC（═O）NRaRb，—NRaC（═O）ORa，—OC（═O）NRaRb或—NHC（═O）Ra，或R1，R2和N共同形成取代的哌嗪，取代的氮杂环丙烷环或取代的吡咯烷环，取代基为—（CH2）2OH或— C（═O）OH；R3是取代或未取代的苯基或5-6成员的杂芳基环，其中取代基为卤素，羟基，氰基，（C1-C15）烷基，（C1-C15）烷氧基或—NRaRb；R4是氢或取代或未取代的（C1-C15）烷基；R5是—（ ）mOR6，—CHNOR7，—C（═O）NR8R9，—（ ）mC（═O）OR10，—（ ）kC（═O）NR11R12；其中，R6是取代或未取代的（C1-C30）烷基，（C3-C10）环烷基或芳基，杂芳基或4-8成员的杂环；R7是氢或取代或未取代的（C1-C30）烷基，（C1-C30）烷基芳基；R8和R9各自独立地是氢或取代或未取代的（C1-C30）烷基，（C1-C30）烷基芳基，（C1-C30）烷基氨基，（C1-C30）烷氧基或饱和或不饱和的单环或双环，碳环或杂环，或R8，N和R9共同形成取代或未取代的4-8成员的杂环；R10是氢或取代或未取代的（C1-C30）烷基，（C3-C10）环烷基，芳基，杂芳基或杂环；R11，N和R12共同形成4-8成员的杂环；Ra和Rb各自独立地是氢或烷基；m为0，1，2或3；k为1，2或3，或其特定对映体，或其特定互变异构体，或其药学上可接受的盐，以及一种用于治疗与A2b腺苷受体相关的疾病的方法，包括向需要这种治疗的受体中施用本发明化合物的治疗有效量。
• HETEROARYL SUBSTITUTED PYRAZOLE DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS AND DISEASES ASSOCIATED WITH ANGIOGENESIS
  申请人：Boyer Stephen

  公开号：US20100249085A1

  公开（公告）日：2010-09-30

  This invention relates to novel heteroaryl substituted pyrazole compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients or therapeutic measures.

  本发明涉及新型杂环取代吡唑化合物、含有这些化合物的药物组合物以及用于治疗过度增殖和/或血管生成障碍的这些化合物或组合物的用途，作为单一药物或与其他活性成分或治疗措施联合使用。
• Heteroaryl substituted pyrazole derivatives useful for treating hyper-proliferative disorders and diseases associated with angiogenesis
  申请人：Boyer Stephen

  公开号：US08796253B2

  公开（公告）日：2014-08-05

  This invention relates to novel heteroaryl substituted pyrazole compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients or therapeutic measures.

  本发明涉及新型杂环取代吡唑化合物、含有这些化合物的药物组合物以及将这些化合物或组合物用于治疗过度增殖和/或血管生成障碍的方法，作为单一药物或与其他活性成分或治疗措施联合使用。