氢喹啉 9-菲基醚 | 135042-88-5

• 物质功能分类: 化学试剂 - 有机试剂 - 多环化合物
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 金鸡纳生物碱
• 中文名称: 氢喹啉 9-菲基醚
• 中文别名: 氢喹啉9-菲基醚
• 英文名称: dihydroquinidine 9-O-(9'-phenanthryl) ether
• 英文别名: Hydroquinidine 9-phenanthryl ether；4-[(S)-[(2R,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-phenanthren-9-yloxymethyl]-6-methoxyquinoline
• CAS: 135042-88-5
• 化学式: C₃₄H₃₄N₂O₂
• 分子量: 502.656
• InChiKey: TWOVHUYOMTVDRB-SAUGTVQKSA-N

物化性质

• 熔点：
  112 °C (dec.)(lit.)
• 沸点：
  690.3±40.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  34.6
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  6.1(b)
• 安全说明：
  S22,S24/25
• WGK Germany：
  3
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险品运输编号：
  UN 1544
• 危险性防范说明：
  P264,P270,P280,P301+P312+P330,P302+P352+P332+P313+P362+P364,P305+P351+P338+P337+P313,P501
• 危险性描述：
  H302,H315,H319
• 储存条件：
  2-8°C

反应信息

• 作为产物：
  描述：

  氢化奎尼定 、 9-碘菲 在 吡啶 、 copper(l) iodide 、 sodium hydride 作用下， 生成 氢喹啉 9-菲基醚
  参考文献：
  名称：

  New ligands double the scope of the catalytic asymmetric dihydroxylation of olefins

  摘要：

  Improved ligands render terminal olefins good substrates for the osmium-catalyzed asymmetric dihydroxylation (ADH) process, and the amounts of chiral ligand and osmium catalyst required diminish dramatically.

  DOI：

  10.1021/jo00015a001
• 作为试剂：
  描述：

  (2R)-3,3-dimethyl-2-(1-(R)-phenyl-ethylamino)-hex-5-enenitrile 在 palladium on activated charcoal 吡啶 、 盐酸 、 氢气 、 potassium carbonate 、 caesium carbonate 、 氢喹啉 9-菲基醚 、 三乙胺 、 对甲苯磺酰氯 、 potassium hexacyanoferrate(III) 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙腈 、 叔丁醇 为溶剂， 生成
  参考文献：
  名称：

  Discovery of 3,3-dimethyl-5-hydroxypipecolic hydroxamate-based inhibitors of aggrecanase and MMP-13

  摘要：

  A series of pipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was discovered based on screening known inhibitors of TNF-alpha converting enzyme (TACE). Potency versus aggrecanase was optimized by modification of the benzyloxyaryl-sulfonamide group. Incorporation of geminal alkyl substitution at the 3-position of the piperidine ring improved metabolic stability, presumably by increasing steric hindrance around the metabolically labile hydroxamic acid. This modification also resulted in dramatic improvement of aggrecanase activity with a slight reduction in selectivity versus MMP-1. Synthesis, structure activity relationships, and strategies to reduce metabolic clearance are described. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.105

文献信息

• Selective inhibition of aggrecanase in osteoarthritis treatment
  申请人：Noe C. Mark

  公开号：US20050227997A1

  公开（公告）日：2005-10-13

  This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC 50 s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs or reprolysins). This invention also relates to compounds, methods of treatment and composition of Formula I: or a therapeutically acceptable salt thereof, wherein X is carbon or nitrogen; R 1 and R 2 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, wherein at least one of R 1 and R 2 is methyl; R 3 and R 4 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, or R 3 and R 4 may be taken together to form a carbonyl group; and R 5 and R 6 are independent substituents in the ortho, meta, or para positions and are independently selected from the group consisting of hydrogen, halogen, cyano, methyl, and ethyl; with the provisos: when X is carbon, then R 7 and R 8 are both hydrogen and at least one of R 1 , R 2 , R 3 , and R 4 is hydroxy; when X is carbon and R 5 is para-halo, then at least one of R 6 , R 3 , and R 4 is not hydrogen; when X is nitrogen, then R 8 is not present and R 7 is hydrogen or a group of the formula: wherein, Y is —CH 2 —NH 2 or —NH—CH 3 ; and when X is nitrogen and R 7 is H, then R 3 and R 4 are taken together to form a carbonyl group.

  这项发明涉及一种治疗骨关节炎的方法，涉及抑制aggrecanase的抑制剂，其IC50小于20 nM，并且对基质金属蛋白酶（MMPs）和脱粒蛋白酶（ADAMs或reprolysins）表现出差异的效力。这项发明还涉及化合物、治疗方法和Formula I的组成： 或其治疗上可接受的盐，其中X为碳或氮； R1和R2分别选自氢、羟基和甲基组成的群，其中至少一个为甲基； R3和R4分别选自氢、羟基和甲基组成的群，或R3和R4可一起形成一个羰基；以及 R5和R6是正交位、间位或对位的独立取代基，分别选自氢、卤素、氰基、甲基和乙基；附加条件： 当X为碳时，R7和R8都是氢，且至少一个R1、R2、R3和R4为羟基； 当X为碳且R5为对位卤素时，至少一个R6、R3和R4不是氢； 当X为氮时，R8不存在且R7为氢或一个公式的基团： 其中，Y为—CH2—NH2或—NH—CH3；以及 当X为氮且R7为H时，R3和R4一起形成一个羰基。
• Selective inhibitors of aggrecanase in osteoarthritis treatment
  申请人：Pfizer Products Inc.

  公开号：EP1081137A1

  公开（公告）日：2001-03-07

  This invention relates to a method of treatment for osteoarthritis involving inhibitors of aggrecanase that demonstrate IC50s of less than 20 nM and demonstrate differential potency against matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinases (ADAMs or reprolysins). This invention also relates to compounds, methods of treatment and composition of Formula I: or a therapeutically acceptable salt thereof, wherein X is carbon or nitrogen; R1 and R2 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, wherein at least one of R1 and R2 is methyl; R3 and R4 are independently selected from the group consisting of hydrogen, hydroxy, and methyl, or R3 and R4 may be taken together to form a carbonyl group; and R5 and R6 are independent substituents in the ortho, meta, or para positions and are independently selected from the group consisting of hydrogen, halogen, cyano, methyl, and ethyl; with the provisos: when X is carbon, then R7 and R8 are both hydrogen and at least one of R1, R2, R3, and R4 is hydroxy; when X is carbon and R5 is para-halo, then at least one of R6, R3, and R4 is not hydrogen; when X is nitrogen, then R8 is not present and R7 is hydrogen or a group of the formula: wherein, Y is -CH2-NH2 or -NH-CH3; and when X is nitrogen and R7 is H, then R3 and R4 are taken together to form a carbonyl group.

  这项发明涉及一种治疗骨关节炎的方法，涉及抑制aggrecanase的方法，其IC50小于20 nM，并且对基质金属蛋白酶（MMPs）和脱粒蛋白酶（ADAMs或reprolysins）表现出差异的效力。该发明还涉及化合物、治疗方法和Formula I的组成： 或其治疗上可接受的盐，其中 X为碳或氮； R1和R2分别选自氢、羟基和甲基组成的群，其中至少一个为甲基； R3和R4分别选自氢、羟基和甲基组成的群，或R3和R4可一起形成羰基；以及 R5和R6是正交位、间位或对位的独立取代基，分别选自氢、卤素、氰基、甲基和乙基组成的群； 附加条件： 当X为碳时，R7和R8均为氢，且R1、R2、R3和R4中至少一个为羟基； 当X为碳且R5为对位卤素时，至少一个R6、R3和R4不是氢； 当X为氮时，R8不存在，R7为氢或下式的基团： 其中，Y为-CH2-NH2或-NH-CH3；以及 当X为氮且R7为H时，R3和R4一起形成羰基。
• Multifunctional catalyst useful in the synthesis of chiral vicinal diols and process for the preparation thereof
  申请人：Council of Scientific and Industrial Research

  公开号：EP1346767A1

  公开（公告）日：2003-09-24

  The present invention relates to a multifunctional reusable catalyst and to a process for the preparation thereof on a single matrix of the support to perform multicomponent reaction in a single pot. The multifunctional catalysts of the invention are useful for the synthesis of chiral vicinal diols by tandem and / or simultaneous reactions involving Heck coupling, N-oxidation and AD reaction of olefins in presence of cinchona alkaloid compounds both as an native one and immobilized one in the said matrix support. This invention also relates to a process for preparing vicinal diols by asymmetric dihydroxylation of olefins in presence of cinchona alkaloid compounds employing reusable multifunctional catalysts as heterogeneous catalysts in place of soluble osmium catalysts.

  本发明涉及一种多功能可重复使用的催化剂，以及一种在单一支撑基质上制备该催化剂的方法，用于在单一锅中执行多组分反应。本发明的多功能催化剂可用于在金鸡纳生物碱化合物的存在下，通过串联和/或同时反应合成手性邻二醇，涉及 Heck 偶联、N-氧化和烯烃的 AD 反应。该催化剂可以作为原生态和固定化的形式存在于所述支撑基质中。本发明还涉及一种通过在金鸡纳生物碱化合物的存在下，利用可重复使用的多功能催化剂作为异质催化剂来代替可溶性的钌催化剂，合成邻二醇的方法。
• Preparation of new layered double hydroxides exchanged with osmate for asymmetric dihydroxylation of olefins to vicinal diols
  申请人：COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH

  公开号：EP1209142A1

  公开（公告）日：2002-05-29

  Layered double hydroxides exchanged with osmate of the formula [MII(1-x)MIIIx(OH)2] [OsO42-]x/2.zH2O wherein MII is a divalent cation selected from the group consisting of Mg2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Ca2+ and MIII is a trivalent ion selected from the group consisting of Al3+, Cr3+, Mn3+, Fe3+ and Co3+, and x is the mole fraction having a value ranging from 0.2 to 0.33, and z is the number of water molecules ranging from 1 to 4, useful as a catalyst, and a process for the preparation thereof and use thereof to manufacture vicinal diols.

  与锇酸盐交换的层状双氢氧化物，其式为[MII(1-x)MIIIx(OH)2][OsO42-]x/2。zH2O 其中 MII 是选自 Mg2+、Mn2+、Fe2+、Co2+、Ni2+、Cu2+、Zn2+ 和 Ca2+ 的二价阳离子，MIII 是选自 Al3+、Cr3+、Mn3+、Fe3+ 和 Co3+ 的三价离子，x 是摩尔分数，其值范围为 0.2至0.33，z为水分子数，范围为1至4，可用作催化剂，及其制备方法和用其制造沧烷二醇的工艺。
• Syntheses and crystal structures of the cinchona alkaloid derivatives used as ligands in the osmium-catalyzed asymmetric dihydroxylation of olefins
  作者：Willi Amberg、Youssef L. Bennani、Raj K. Chadha、Gerard A. Crispino、William D. Davis、Jens Hartung、Kyu Sung Jeong、Yasukazu Ogino、Tomoyuki Shibata、K. Barry Sharpless

  DOI：10.1021/jo00056a015

  日期：1993.2

  Experimental procedures for the preparation of two classes of derivatives of the cinchona alkaloids dihydroquinine and dihydroquinidine are described. Ligands (DHQ)2-PHAL, la, and (DHQD)2-PHAL, 2a, are conveniently synthesized in good yield by the reaction of the corresponding alkaloid with 1,4-dichlorophthalazine in the presence of K2CO3 and KOH in refluxing toluene. Derivatives DHQ-PHN, lb, and DHQD-PHN, 2b, are prepared through an Ullmann-type coupling between the 9-0-alkaloid sodium alkoxide and 9-iodophenanthrene in the presence of CuI and pyridine. Crystal structures for derivatives 2a and 2b are also presented. These four alkaloid derivatives serve as highly enantioselective ligands for the osmium tetraoxide catalyzed asymmetric dihydroxylation (AD) of olefins.