1-[4-(1-methoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-piperidin-1-yl]-ethanone | 648897-82-9

• 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-[4-(1-methoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-piperidin-1-yl]-ethanone
• 英文别名: 4-(1-Methoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-piperidin-1-yl-ethanone；1-[4-(1-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl)piperidin-1-yl]ethanone
• CAS: 648897-82-9
• 化学式: C₁₈H₂₅NO₂
• 分子量: 287.402
• InChiKey: ISQUWANUVCLWRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-[4-(1-methoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-piperidin-1-yl]-ethanone 在 sodium hydroxide 、 水 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以88.5%的产率得到4-(1-methoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-piperidine
  参考文献：
  名称：

  [EN] ARYL PIPERIDINE DERIVATIVES AS INDUCERS OF LDL-RECEPTOR EXPRESSION FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA
  [FR] DERIVES D'ARYL PIPERIDINE UTILISES COMME INDUCTEURS D'EXPRESSION DES RECEPTEURS DES LIPOPROTEINES DE BASSE DENSITE (LDL) PERMETTANT DE TRAITER L'HYPERCHOLESTEROLEMIE

  摘要：

  这项发明涉及促进低密度脂蛋白受体（LDL-r）表达的新化合物，以及它们的制备方法、含有它们的药物组合物和它们的医疗用途。更具体地说，这项发明涉及式（I）的新芳香基哌啶及其在治疗中的应用。其中Ar1被至少一个R1基团取代，所述R1基团选自：-O(CRaRb)nC(O)NRXRy，-O(CH2)nCN，-O(CH2)nO(CH2)mOR2，-O(CH2)nCO2R2，-OS02NRxRy，-OSO2(CH2)pCH3，-(CRaRb)nC(O)NRXRy，-(CH2)nCN，-(CH2)nO(CH2)mOR2，-(CH2)nCO2R2，-(CH2)nC(O)R2，-SO2NRxRy，-SO2(CH2)pCH3，-CH=CHC(O)NRxRy，-CH=CHCN，-CH=CHCO2R2，-CO2R2，-C(O)R2，-C(O)NRxRy和C2-5烯基。

  公开号：

  WO2004006923A1
• 作为产物：
  描述：

  1-[4-(1-hydroxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-piperidin-1-yl]-ethanone 、 碘甲烷 在 sodium hydride 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 2.0h， 以100%的产率得到1-[4-(1-methoxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-piperidin-1-yl]-ethanone
  参考文献：
  名称：

  [EN] ARYL PIPERIDINE DERIVATIVES AS INDUCERS OF LDL-RECEPTOR EXPRESSION FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA
  [FR] DERIVES D'ARYL PIPERIDINE UTILISES COMME INDUCTEURS D'EXPRESSION DES RECEPTEURS DES LIPOPROTEINES DE BASSE DENSITE (LDL) PERMETTANT DE TRAITER L'HYPERCHOLESTEROLEMIE

  摘要：

  这项发明涉及促进低密度脂蛋白受体（LDL-r）表达的新化合物，以及它们的制备方法、含有它们的药物组合物和它们的医疗用途。更具体地说，这项发明涉及式（I）的新芳香基哌啶及其在治疗中的应用。其中Ar1被至少一个R1基团取代，所述R1基团选自：-O(CRaRb)nC(O)NRXRy，-O(CH2)nCN，-O(CH2)nO(CH2)mOR2，-O(CH2)nCO2R2，-OS02NRxRy，-OSO2(CH2)pCH3，-(CRaRb)nC(O)NRXRy，-(CH2)nCN，-(CH2)nO(CH2)mOR2，-(CH2)nCO2R2，-(CH2)nC(O)R2，-SO2NRxRy，-SO2(CH2)pCH3，-CH=CHC(O)NRxRy，-CH=CHCN，-CH=CHCO2R2，-CO2R2，-C(O)R2，-C(O)NRxRy和C2-5烯基。

  公开号：

  WO2004006923A1

文献信息

• [EN] ARYL PIPERIDINE DERIVATIVES AS INDUCERS OF LDL-RECEPTOR EXPRESSION FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA<br/>[FR] DERIVES D'ARYL PIPERIDINE UTILISES COMME INDUCTEURS D'EXPRESSION DES RECEPTEURS DES LIPOPROTEINES DE BASSE DENSITE (LDL) PERMETTANT DE TRAITER L'HYPERCHOLESTEROLEMIE
  申请人：GLAXO GROUP LTD

  公开号：WO2004006923A1

  公开（公告）日：2004-01-22

  This invention relates to novel compounds which up-regulate LDL receptor (LDL-r) expression. and to processes for their preparation, pharmaceutical compositions containing them and their medical use. More particularly, this invention relates to novel aromatic piperidines of formula (I) and their use in therapy. wherein Ar1 is substituted, by at least one R1 group selected from: -O(CRaRb)nC(O)NRXRy, -O(CH2)nCN, -O(CH2)nO(CH2)mOR2, -O(CH2)nCO2R2, -OS02NRxRy, -OSO2(CH2)pCH3, -(CRaRb)nC(O)NRXRy, -(CH2)nCN, -(CH2)nO(CH2)mOR2, -(CH2)nCO2R2, -(CH2)nC(O)R2, - SO2NRxRy, -SO2(CH2)pCH3, -CH=CHC(O)NRxRy, -CH=CHCN, -CH=CHCO2R2, -CO2R2, - C(O)R2, -C(O)NRxRy and C2-5alkenyl.

  这项发明涉及促进低密度脂蛋白受体（LDL-r）表达的新化合物，以及它们的制备方法、含有它们的药物组合物和它们的医疗用途。更具体地说，这项发明涉及式（I）的新芳香基哌啶及其在治疗中的应用。其中Ar1被至少一个R1基团取代，所述R1基团选自：-O(CRaRb)nC(O)NRXRy，-O(CH2)nCN，-O(CH2)nO(CH2)mOR2，-O(CH2)nCO2R2，-OS02NRxRy，-OSO2(CH2)pCH3，-(CRaRb)nC(O)NRXRy，-(CH2)nCN，-(CH2)nO(CH2)mOR2，-(CH2)nCO2R2，-(CH2)nC(O)R2，-SO2NRxRy，-SO2(CH2)pCH3，-CH=CHC(O)NRxRy，-CH=CHCN，-CH=CHCO2R2，-CO2R2，-C(O)R2，-C(O)NRxRy和C2-5烯基。
• Aryl piperidine derivatives as inducers of ldl-receptor expression
  申请人：——

  公开号：US20040147557A1

  公开（公告）日：2004-07-29

  The invention relates to a compound of formula (I), wherein Ar 1 represents phenyl, naphthyl or phenyl fused by a C 3-8 cycloalkyl, where each group is optionally substituted by methylenedioxy or one or two groups independently represented by R 1 ; Ar 2 represents phenyl or a 5-6 membered heteroaromatic group, where each group is optionally substituted by one to four groups independently selected from halogen, C 1-4 alkyl and C 1-4 alkoxy; Ar 3 represents a phenyl or a 5-6 membered heteroaromatic group, where each group is optionally substituted by one to four groups independently selected from hydroxy, alkyl, C 1-4 alkoxy, C 2-4 alkenyl, C 2-4 alkenyloxy, C 1-4 perfluoroalkoxy, C 1-4 acylamino or an electron withdrawing group; A represents —C(H)—; E represents —C 1-6 alkylene-; X represents —CON(H or C 1-4 alkyl)- or —N(H or C 1-4 alkyl)CO—; Y represents a direct link; R 1 represents halogen, —S(C 1-4 alkyl)-, —O—(C 0-4 alkylene)-R 2 or —(C 0-4 alkylene)-R 2 , where each alkylene group may additionally incorporate an oxygen in the chain, with the proviso that there are at least two carbon atoms between any chain heteroatoms; R 2 represents: i) hydrogen, C 1-4 perfluoroalkyl, C 2-3 alkenyl, ii) phenyl, naphthyl, a 5- or 6-membered heteroaromatic group or 1,2,3,4-tetrahydronaphthyl, optionally substituted by one or two halogen, hydroxy, C 1-4 alkyl, C 1-4 alkoxy groups, iii) C 3-8 cycloalkyl, a 3-7 membered heterocycloalkyl, iv) amino, C 1-4 alkylamino or di-C 1-4 alkylamino, with the proviso that there are at least two carbon atoms between any chain heteroatoms; to salts, solvates and compositions thereof and their use in treating disorders associated with elevated levels of circulating LDL-cholesterol. 1

  本发明涉及一种式（I）的化合物，其中Ar1代表苯基，萘基或由C3-8环烷基融合的苯基，其中每个基团可以被甲亚氧基或由R1独立表示的一或两个基团取代；Ar2代表苯基或5-6成员杂芳基，其中每个基团可以被从卤素、C1-4烷基和C1-4烷氧基中独立选择的1到4个基团取代；Ar3代表苯基或5-6成员杂芳基，其中每个基团可以被从羟基、烷基、C1-4烷氧基、C2-4烯基、C2-4烯氧基、C1-4全氟烷氧基、C1-4酰胺基或电子吸引基中独立选择的1到4个基团取代；A代表-C（H）-；E代表-C1-6烷基-；X代表—CON（H或C1-4烷基）-或—N（H或C1-4烷基）CO-；Y代表直接连接；R1代表卤素、—S（C1-4烷基）-、—O—（C0-4烷基）-R2或—（C0-4烷基）-R2，其中每个烷基组可能在链中还包含一个氧原子，但必须保证链中任何异原子之间至少有两个碳原子；R2代表：i）氢、C1-4全氟烷基、C2-3烯基，ii）苯基、萘基、5-或6-成员杂芳基或1,2,3,4-四氢萘基，可以选择地被1或2个卤素、羟基、C1-4烷基、C1-4烷氧基取代，iii）C3-8环烷基、3-7成员杂环烷基，iv）氨基、C1-4烷基氨基或二-C1-4烷基氨基，但必须保证链中任何异原子之间至少有两个碳原子；以及其盐、溶剂化合物和组合物及其用于治疗与循环低密度脂蛋白胆固醇水平升高相关的疾病的用途。
• Aryl piperidine derivatives as inducers of ldl-receptor expression for the treatment of hypercholesterolemia
  申请人：Bouillot Jeanne Anne Marie

  公开号：US20060052384A1

  公开（公告）日：2006-03-09

  This invention relates to novel compounds which up-regulate LDL receptor (LDL-r) expression and to processes for their preparation, pharmaceutical compositions containing them and their medical use. More particularly, this invention relates to novel aromatic piperidines and their use in therapy.

  本发明涉及一种新型化合物，其上调LDL受体（LDL-r）表达，并涉及其制备过程、含有它们的制药组合物及其医学用途。更具体地说，本发明涉及新型芳香基哌啶及其在治疗中的应用。
• ARYL PIPERIDINE DERIVATIVES AS INDUCERS OF LDL-RECEPTOR EXPRESSION
  申请人：GLAXO GROUP LIMITED

  公开号：EP1351937A1

  公开（公告）日：2003-10-15
• [EN] ARYL PIPERIDINE DERIVATIVES AS INDUCERS OF LDL-RECEPTOR EXPRESSION<br/>[FR] DERIVES D'ARYLEPIPERIDINE UTILISES COMME INDUCTEURS D'EXPRESSION DE LDL
  申请人：GLAXO GROUP LTD

  公开号：WO2002055497A1

  公开（公告）日：2002-07-18

  The invention relates to a compound of formula (I), wherein Ar1 represents phenyl, naphthyl or phenyl fused by a C3-8cycloalkyl, where each group is optionally substituted by methylenedioxy or one or two groups independently represented by R1; Ar2 represents phenyl or a 5-6 membered heteroaromatic group, where each group is optionally substituted by one to four groups independently selected from halogen, C1-4 alkyl and C1-4 alkoxy; Ar3 represents a phenyl or a 5-6 membered heteroaromatic group, where each group is optionally substituted by one to four groups independently selected from hydroxy, alkyl, C1-4 alkoxy, C2-4 alkenyl, C2-4 alkenyloxy, C1-4 perfluoroalkoxy, C1-4 acylamino or an electron withdrawing group; A represents -C(H)-; E represents -C1-6 alkylene-; X represents -CON(H or C1-4alkyl)- or -N(H or C1-4alkyl)CO-; Y represents a direct link; R1 represents halogen, -S(C¿1-4? alkyl)-, -O-(C0-4 alkylene)-R?2¿ or -(C¿0-4?alkylene)-R?2¿, where each alkylene group may additionally incorporate an oxygen in the chain, with the proviso that there are at least two carbon atoms between any chain heteroatoms; R2 represents: i) hydrogen, C¿1-4? perfluoroalkyl, C2-3 alkenyl, ii) phenyl, naphthyl, a 5- or 6-membered heteroaromatic group or 1,2,3,4-tetrahydronaphthyl, optionally substituted by one or two halogen, hydroxy, C1-4 alkyl, C1-4 alkoxy groups, iii) C3-8cycloalkyl, a 3-7 membered heterocycloalkyl, iv) amino, C1-4 alkylamino or di-C1-4alkylamino, with the proviso that there are at least two carbon atoms between any chain heteroatoms; to salts, solvates and compositions thereof and their use in treating disorders associated with elevated levels of circulating LDL-cholesterol.