1-(6-benzyloxynaphthalen-2-yl)piperidin-4-ol | 1381986-28-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(6-benzyloxynaphthalen-2-yl)piperidin-4-ol
• 英文别名: 1-(6-(benzyloxy)naphthalen-2-yl)piperidin-4-ol；1-(6-Phenylmethoxynaphthalen-2-yl)piperidin-4-ol
• CAS: 1381986-28-2
• 化学式: C₂₂H₂₃NO₂
• 分子量: 333.43
• InChiKey: DGPMMUICIWBWDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(6-benzyloxynaphthalen-2-yl)piperidin-4-ol 在 palladium 10% on activated carbon 、 三氟化硼乙醚 、 氢气 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 52.0h， 生成 1-(5-(4-(2-morpholinoethoxy)benzyl)-6-hydroxynaphthalen-2-yl)piperidin-4-ol
  参考文献：
  名称：

  Design, synthesis and bioevaluation of novel 6-(4-Hydroxypiperidino)naphthalen-2-ol-based potential Selective Estrogen Receptor Modulators for breast cancer

  摘要：

  In a study directed towards development of novel Selective Estrogen Receptor Modulators (SERMs), 1-(4-(2-(dialkylamino)ethoxy)benzyl)-6-(4-hydroxypiperidin-1-yl)-2-naphthol and corresponding aryl methyl ethers were synthesized and bioevaluated against the estrogen-responsive human MCF-7 breast cancer cell line. The phenolic analogs displayed little or no activity, but aryl methyl ether analogs showed significant cytotoxic potency. Also, representative compounds from the aryl methyl ether series showed significant binding and antagonistic activity against ER alpha. Two representative compounds were also evaluated for in vitro membrane permeability, plasma stability as well as in-vivo toxicity in mice. The compounds displayed well-acceptable drug-like in vitro membrane permeability as well as plasma stability and were well-tolerated in experimental mice at 300 mg/kg dose. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.037
• 作为产物：
  描述：

  4-羟基哌啶 、 2-苄氧基-6-溴萘 在 copper(l) iodide 、 potassium carbonate 、 L-脯氨酸 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 以69%的产率得到1-(6-benzyloxynaphthalen-2-yl)piperidin-4-ol
  参考文献：
  名称：

  Design, synthesis and bioevaluation of novel 6-(4-Hydroxypiperidino)naphthalen-2-ol-based potential Selective Estrogen Receptor Modulators for breast cancer

  摘要：

  In a study directed towards development of novel Selective Estrogen Receptor Modulators (SERMs), 1-(4-(2-(dialkylamino)ethoxy)benzyl)-6-(4-hydroxypiperidin-1-yl)-2-naphthol and corresponding aryl methyl ethers were synthesized and bioevaluated against the estrogen-responsive human MCF-7 breast cancer cell line. The phenolic analogs displayed little or no activity, but aryl methyl ether analogs showed significant cytotoxic potency. Also, representative compounds from the aryl methyl ether series showed significant binding and antagonistic activity against ER alpha. Two representative compounds were also evaluated for in vitro membrane permeability, plasma stability as well as in-vivo toxicity in mice. The compounds displayed well-acceptable drug-like in vitro membrane permeability as well as plasma stability and were well-tolerated in experimental mice at 300 mg/kg dose. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.12.037

文献信息

• [EN] SELECTIVE ESTROGEN RECEPTOR MODULATORS<br/>[FR] MODULATEURS SÉLECTIFS DES RÉCEPTEURS DES OESTROGÈNES
  申请人：UNIV DALHOUSIE

  公开号：WO2012079154A1

  公开（公告）日：2012-06-21

  The invention provides compounds of Formula (I) : wherein R1 is hydrogen, OH, halo, -CN, -NO2, -N=0, -NHOQ2, -OQ2, -SOQ2, -SO2Q2, -SON(Q2)2, - SO2N(Q2)2, -N(Q2)2, -C(O)OQ2, -C(O)Q2, -C(O)N(Q2)2, -C(=NQ2)NQ2, -NQ2C(=NQ2)NQ2, - C(O)N(Q2)(OQ2), -N(Q2)C(O)-Q2, -N(Q2)C(O)N(Q2)2, -N(Q2)C(O)O-Q2, -N(Q2)SO2Q2, -N(Q2)SOQ2, aliphatic, alkoxy, cycloaliphatic, aryl, arylalkyl, heterocyclic, or heteroaryl ring, each aliphatic, alkoxy, cycloaliphatic, aryl, arylalkyl, heterocyclic, and heteroaryl ring optionally including 1-3 substituents independently selected Q3; R2 and R3 are each independently hydrogen, OH, oxo, aliphatic, cycloaliphatic, heterocycloaliphatic, aryl, or heteroaryl, optionally substituted with 1-3 of Q1 or Q2; X is a branched or straight C1-12 aliphatic chain wherein up to two carbon units are optionally and independently replaced by -C(Q1)2-, -C(Q2)2-, CHQ1, CHQ2-, -CO-, -CS-, -CONQ2, -CO2-, -OCO-, -NQ2-, -NQ2CO2-, - O-, -NQ2CONQ2-, -OCONQ2-, -NQ2CO-, -S-, -SO-, -SO2-, -SO2NQ2-, -NQ2SO2-, or -NQ2SO2NQ2-; G and G1 are each independently a branched or straight C1-2 aliphatic chain, or heterocycloalkyl, wherein up to two carbon units are optionally and independently replaced by -C(Q1)2-, -C(Q2)2-, CHQ1, CHQ2-, -CO-, - CS-, -CONQ2, -CO2-, -OCO-, -NQ2-, -NQ2CO2-, -O-, -NQ2CONQ2-, -OCONQ2-, -NQ2CO-, -S-, -SO-, - SO2-, -SO2NQ2-, -NQ2SO2-, or -NQ2SO2NQ2-, and pharmaceutically acceptable salts, solvates or prodaigs thereof, as well as methods of treating estrogen receptor mediated diseases and disorders using the compounds of Formula (I).

  该发明提供了Formula (I)的化合物：其中R1是氢、OH、卤素、-CN、-NO2、-N=0、-NHOQ2、-OQ2、-SOQ2、-SO2Q2、-SON(Q2)2、-SO2N(Q2)2、-N(Q2)2、-C(O)OQ2、-C(O)Q2、-C(O)N(Q2)2、-C(=NQ2)NQ2、-NQ2C(=NQ2)NQ2、-C(O)N(Q2)(OQ2)、-N(Q2)C(O)-Q2、-N(Q2)C(O)N(Q2)2、-N(Q2)C(O)O-Q2、-N(Q2)SO2Q2、-N(Q2)SOQ2、脂肪族、烷氧基、环脂肪族、芳基、芳基烷基、杂环、或杂芳基环，每个脂肪族、烷氧基、环脂肪族、芳基、芳基烷基、杂环和杂芳基环可选地包括1-3个独立选择的Q3取代基；R2和R3分别独立地是氢、OH、氧化物、脂肪族、环脂肪族、杂环脂肪族、芳基或杂芳基，可选地取代为1-3个Q1或Q2；X是分支或直链C1-12脂肪链，其中最多两个碳单位可选地和独立地被-C(Q1)2-、-C(Q2)2-、CHQ1、CHQ2-、-CO-、-CS-、-CONQ2、-CO2-、-OCO-、-NQ2-、-NQ2 -、-O-、-NQ2CONQ2-、-OCONQ2-、-NQ2CO-、-S-、-SO-、-SO2-、-SO2NQ2-、-NQ2SO2-或-NQ2SO2NQ2-取代；G和G1分别独立地是分支或直链C1-2脂肪链，或杂环脂肪族，其中最多两个碳单位可选地和独立地被-C(Q1)2-、-C(Q2)2-、CHQ1、CHQ2-、-CO-、-CS-、-CONQ2、- -、-OCO-、-NQ2-、-NQ2 -、-O-、-NQ2CONQ2-、-OCONQ2-、-NQ2CO-、-S-、-SO-、-SO2-、-SO2NQ2-、-NQ2SO2-或-NQ2SO2NQ2-取代；以及药学上可接受的盐、溶剂或其制品，以及使用Formula (I)的化合物治疗雌激素受体介导的疾病和疾病的方法。