1-[4-(1-hydroxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-3,6-dihydro-2H-pyridin-1-yl]-ethanone | 443131-03-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 1-[4-(1-hydroxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-3,6-dihydro-2H-pyridin-1-yl]-ethanone
• 英文别名: 1-[4-(1-hydroxy-5,6,7,8-tetrahydronaphthalen-2-yl)-3,6-dihydro-2H-pyridin-1-yl]ethanone
• CAS: 443131-03-1
• 化学式: C₁₇H₂₁NO₂
• 分子量: 271.359
• InChiKey: SALRYBRBXUHJIE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-[4-(1-hydroxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-3,6-dihydro-2H-pyridin-1-yl]-ethanone 在 palladium 10% on activated carbon 氢气 作用下， 以 乙醇 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 生成 1-[4-(1-hydroxy-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 DE PIPERIDINE-ARYLE SERVANT D'INDUCTEURS DE L'EXPRESSION DU RECEPTEUR LDL POUR LE TRAITEMENT DE L'HYPERCHOLESTEROLEMIE

  摘要：

  这项发明涉及一种新型化合物，可以上调LDL受体（LDL-r）的表达，并涉及其制备过程、含有它们的药物组合物以及它们的医疗用途。更具体地，这项发明涉及式（I）的新型芳香基哌啶及其在治疗中的应用。

  公开号：

  WO2004006922A1
• 作为产物：
  描述：

  N-乙酰基-4-哌啶酮 、 四氢萘酚 在 三氟化硼乙醚 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 以66%的产率得到1-[4-(1-hydroxy-5,6,7,8-tetrahydro-naphthalen-2-yl)-3,6-dihydro-2H-pyridin-1-yl]-ethanone
  参考文献：
  名称：

  [EN] ARYL PIPERIDINE DERIVATIVES AND USE THEREOF TO REDUCE ELEVATED LEVELS OF LDL-CHOLESTEROL
  [FR] DERIVES D'ARYLE PIPERIDINE ET UTILISATION DE CEUX-CI POUR REDUIRE DES TAUX ELEVES DE LDL-CHOLESTEROL

  摘要：

  这项发明涉及一种新型化合物，可以上调LDL受体（LDL-r）的表达，并涉及其制备方法、含有它们的药物组合物以及它们的医疗用途。更具体地说，这项发明涉及新型芳香基哌啶类化合物及其在治疗中的应用。

  公开号：

  WO2004006924A1

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。
• [EN] ARYL PIPERIDINE DERIVATIVES AND USE THEREOF TO REDUCE ELEVATED LEVELS OF LDL-CHOLESTEROL<br/>[FR] DERIVES D'ARYLE PIPERIDINE ET UTILISATION DE CEUX-CI POUR REDUIRE DES TAUX ELEVES DE LDL-CHOLESTEROL
  申请人：GLAXO GROUP LTD

  公开号：WO2004006924A1

  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 and their use in therapy.

  这项发明涉及一种新型化合物，可以上调LDL受体（LDL-r）的表达，并涉及其制备方法、含有它们的药物组合物以及它们的医疗用途。更具体地说，这项发明涉及新型芳香基哌啶类化合物及其在治疗中的应用。
• [EN] ARYL PIPERIDINE DERIVATIVES AS INDUCERS OF LDL-RECEPTOR EXPRESSION FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA<br/>[FR] DERIVES D'ARYLE PIPERIDINE SERVANT D'INDUCTEURS DE L'EXPRESSION DU RECEPTEUR LDL POUR LE TRAITEMENT DE L'HYPERCHOLESTEROLEMIE
  申请人：GLAXO GROUP LTD

  公开号：WO2004007493A1

  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 Ar1is substituted by at least one R' group selected from: -O(CRaRb)nC(O)NRxRy,. -O(CH2)nCN, -O(CH2)nO(CH2)mOR2, -O(CH2)nCO2R2, -OSO2NRXRy, -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; and Ar2 is substituted by 1-4 groups independently selected from the group consisting of: (CH2)nOH and -C02(CH2)pCH3.

  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）的新芳香哌啶类化合物及其在治疗中的应用。其中Ar1被至少一个R'基取代，所述R'基选自以下基团之一：-O(CRaRb)nC(O)NRxRy、-O(CH2)nCN、-O(CH2)nO(CH2)mOR2、-O(CH2)nCO2R2、-OSO2NRXRy、-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；Ar2被独立选择的1-4个基团取代，所述基团选自(CH2)nOH和-C02(CH2)pCH3。
• Aryl piperidine and piperazine derivatives as inducers of ldl-receptor expression
  申请人：——

  公开号：US20040077654A1

  公开（公告）日：2004-04-22

  The invention concerns Use of a compound of formula (I) or a physiologically acceptable salt, solvate or derivative thereof, in the manufacture of a medicament for the treatment of diseases ameliorated by LDL-r upregulation, to novel compounds and pharmaceutical compositions within the scope of formula (I).

  该发明涉及使用式(I)的化合物或其生理上可接受的盐、溶剂合物或衍生物，用于制造治疗通过LDL-r上调改善的疾病的药物，以及在式(I)范围内的新化合物和药物组合物。
• Aryl piperidine derivatives as inducers of ldl-receptor expression
  申请人：——

  公开号：US20040072865A1

  公开（公告）日：2004-04-15

  The invention concerns a compound of formula (I), wherein Ar 1 represents phenyl, naphthyl or phenyl fused by a C 3-8 cycloalkyl, where each group is substituted by a group —O-Z and optionally one to three further groups independently represented by R 1 ; Ar 2 represents phenyl or 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, —N(H or C 1-4 alkyl)CO— or —CON(H or C 1-4 alkyl)-; Z represents a metabolically labile group; 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; and physiologically acceptable salts, solvates and pharmaceutical compositions thereof and their use in treating disorders associated with elevated circulating levels of LDL-cholesterol.

  本发明涉及公式（I）的化合物，其中Ar1代表苯基，萘基或被C3-8环烷基融合的苯基，其中每个基都被-O-Z基取代，且可以有一到三个进一步独立表示为R1的基；Ar2代表苯基或5-6成员杂环芳基，其中每个基可选地被从卤素，C1-4烷基和C1-4烷氧基中独立选择的一到四个基取代；Ar3代表苯基或5-6成员杂环芳基，其中每个基可选地被从羟基，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酰胺基或电子提取基中独立选择的一到四个基取代；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，-N（H或C1-4烷基）CO-或-CON（H或C1-4烷基）-；Z代表代谢易变基团；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括一个氧，但前提是在任何链杂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-成员杂环芳基或1,2,3,4-四氢萘基，可选地被一到两个卤素，羟基，C1-4烷基，C1-4烷氧基取代，iii）C3-8环烷基，3-7成员杂环环烷基，iv）氨基，C1-4烷基氨基或双C1-4烷基氨基，但前提是在任何链杂原子之间至少有两个碳原子；以及其生理上可接受的盐，溶剂化物和制药组合物及其用于治疗与LDL-胆固醇循环水平升高相关的疾病。