methyl ­2-­(6-­methoxynaphthalen-­2-­yl)-­2-­methylpropanoate | 69337-84-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl ­2-­(6-­methoxynaphthalen-­2-­yl)-­2-­methylpropanoate
• 英文别名: methyl 2-(6-methoxynaphthalen-2-yl)-2-methylpropanoate；methyl α-(6-methoxynaphthalen-2-yl)isobutyrate；α,α-dimethyl-6-methoxy-2-naphthaleneacetic acid methyl ester；alpha,alpha-Dimethyl-6-methoxy-2-naphthaleneacetic acid methyl ester
• CAS: 69337-84-4
• 化学式: C₁₆H₁₈O₃
• 分子量: 258.317
• InChiKey: XAHFBCKECDPBLV-UHFFFAOYSA-N

物化性质

• 沸点：
  370.9±17.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl ­2-­(6-­methoxynaphthalen-­2-­yl)-­2-­methylpropanoate 在 potassium trimethylsilonate 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以92%的产率得到2-(6-甲氧基-2-萘)-2-甲基丙酸
  参考文献：
  名称：

  Substrate-Selective Inhibition of Cyclooxygenase-2: Development and Evaluation of Achiral Profen Probes

  摘要：

  Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds and evaluated them for substrate-selective inhibition using in vitro and cellular assays. The size of the substituents dictated the inhibitory strength of the analogs, with smaller substituents enabling greater potency but less selectivity. Inhibitors based on the flurbiprofen scaffold possessed the greatest potency and selectivity, with desmethylflurbiprofen (3a) exhibiting an IC50 of 0.11 mu M for inhibition of 2-AG oxygenation. The crystal structure of desmethylflurbiprofen complexed to mCOX-2 demonstrated a similar binding mode to other profens. Desmethylflurbiprofen exhibited a half-life in mice comparable to that of ibuprofen. The data presented suggest that achiral profens can act as lead molecules toward in vivo probes of substrate-selective COX-2 inhibition.

  DOI：

  10.1021/ml3001616
• 作为产物：
  描述：

  2-(6-甲氧基-2-萘基)丙酸 在 硫酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 methyl ­2-­(6-­methoxynaphthalen-­2-­yl)-­2-­methylpropanoate
  参考文献：
  名称：

  Substrate-Selective Inhibition of Cyclooxygenase-2: Development and Evaluation of Achiral Profen Probes

  摘要：

  Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds and evaluated them for substrate-selective inhibition using in vitro and cellular assays. The size of the substituents dictated the inhibitory strength of the analogs, with smaller substituents enabling greater potency but less selectivity. Inhibitors based on the flurbiprofen scaffold possessed the greatest potency and selectivity, with desmethylflurbiprofen (3a) exhibiting an IC50 of 0.11 mu M for inhibition of 2-AG oxygenation. The crystal structure of desmethylflurbiprofen complexed to mCOX-2 demonstrated a similar binding mode to other profens. Desmethylflurbiprofen exhibited a half-life in mice comparable to that of ibuprofen. The data presented suggest that achiral profens can act as lead molecules toward in vivo probes of substrate-selective COX-2 inhibition.

  DOI：

  10.1021/ml3001616

文献信息

• Quinoline substituted naphthalenepropionic acid derivatives as
  申请人：American Home Products Corporation

  公开号：US05084575A1

  公开（公告）日：1992-01-28

  There are disclosed compounds of the formula ##STR1## wherein a is alkyl 3-19 carbon atoms, diloweralkyl allyl, diahaloallyl, diphenylallyl, lower alkynyl, ##STR2## W is --CR.sub.2 O--, --CH.dbd.CH-- or --CH.dbd.CHCH.sub.2 O-- X is N or CR; Z is ##STR3## R is hydrogen or lower alkyl; Y is ##STR4## R.sup.1 is hydrogen, lower alkyl or phenyl; R.sup.2 is hydrogen or lower alkyl; or R.sup.1 and R.sup.2 taken together form a benzene ring, optionally substituted by halo; R.sup.3 is --OR, ##STR5## -- NHSO.sub.2 R.sup.4 ; R.sup.4 is phenyl or loweralkyl substituted phenyl; R.sup.5 is halo; and the pharmaceutically acceptable salts thereof, and their use in the treatment of leukotriene-mediated naso-bronchial obstructive airpassageway conditions, such as alelrgic rhinitis, allergic bronchial asthma and the like, in psoriasis, ulcerative colitis, rheumatoid arthritis as well as in other immediate hypersensitivity reactions.

  给定的化合物公式为##STR1##，其中a是烷基，含有3-19个碳原子，二次烷基烯丙基，二卤代烯丙基，二苯基烯丙基，低炔基，##STR2## W是--CR.sub.2 O--，--CH.dbd.CH--或--CH.dbd.CHCH.sub.2 O-- X是N或CR；Z是##STR3## R是氢或低烷基；Y是##STR4## R.sup.1是氢，低烷基或苯基；R.sup.2是氢或低烷基；或者R.sup.1和R.sup.2一起形成苯环，可以选择地被卤素取代；R.sup.3是--OR，##STR5## -- NHSO.sub.2 R.sup.4；R.sup.4是苯基或低烷基取代的苯基；R.sup.5是卤素；以及它们的药用盐，以及它们在治疗白三烯介导的鼻支气管阻塞气道疾病中的用途，例如过敏性鼻炎，过敏性支气管哮喘等，在牛皮癣，溃疡性结肠炎，类风湿性关节炎以及其他即时超敏反应中。
• Quinolinylmethoxy naphthalenepropionic acid derivatives as
  申请人：American Home Products Corporation

  公开号：US05250693A1

  公开（公告）日：1993-10-05

  There are disclosed compounds of the formula ##STR1## wherein R is hydrogen or lower alkyl; Y is ##STR2## or a pharmaceutically acceptable salt thereof, and its use in the treatment of leukotriene-mediated naso-bronchial obstructive airpassageway conditions, such as allergic rhinitis, allergic bronchial asthma and the like, in psoriasis, ulcerative colitis, rheumatoid arthritis as well as in other immediate hypersensitivity reactions.

  公开了化合物的结构式为##STR1##其中R是氢或较低的烷基；Y是##STR2##或其药学上可接受的盐，并且其在治疗白三烯介导的鼻支气管阻塞性气道疾病，如过敏性鼻炎，过敏性支气管哮喘等，牛皮癣，溃疡性结肠炎，类风湿性关节炎以及其他即时型超敏反应中的用途。
• Efficient Synthesis of α-Aryl Esters by Room-Temperature Palladium-Catalyzed Coupling of Aryl Halides with Ester Enolates
  作者：Morten Jørgensen、Sunwoo Lee、Xiaoxiang Liu、Joanna P. Wolkowski、John F. Hartwig

  DOI：10.1021/ja027643u

  日期：2002.10.1

  arylation of alpha,alpha-disubstituted esters were developed with LiNCy(2) as base and P(t-Bu)(3) as ligand. In addition, tert-butyl esters, such as those of Naproxen and Flurbiprofen, were prepared from tert-butyl propionate and aryl bromides in high yields in the presence of Pd(dba)(2) and the hindered, saturated heterocyclic carbene ligand precursor.

  催化量的 Pd(dba)(2) 由卡宾前体 N,N'-双(2,6-二异丙基苯基)-4,5-二氢咪唑鎓 (1) 或 P(t-Bu)(3) 介导芳基卤化物和酯烯醇化物在室温下以高产率偶联产生α-芳基酯。该反应对芳基卤化物上的官能团和取代模式具有高度耐受性。使用 LiNCy(2) 作为基础和 P(t-Bu)(3) 作为配体开发了用于选择性单芳基化乙酸叔丁酯和 α、α-二取代酯的有效芳基化的改进方案。此外，在 Pd(dba)(2) 和受阻饱和杂环卡宾配体前体存在下，由丙酸叔丁酯和芳基溴化物以高产率制备叔丁酯，例如萘普生和氟比洛芬。
• Naphthalenepropionic acid derivatives as anti-inflammatory/antiallergic
  申请人：American Home Products Corporation

  公开号：US05208344A1

  公开（公告）日：1993-05-04

  There are disclosed compounds of the formula ##STR1## wherein A is alkyl of 3-19 carbon atoms, diloweralkyl allyl, dihaloallyl, diphenylallyl, lower alkynyl, ##STR2## with the proviso that A is not quinolinyl; W is --CR.sub.2 O--, --CH.dbd.CH-- or --CH.dbd.CHCH.sub.2 O--; X is N or CR; Z is ##STR3## --S-- or --O--; R is hydrogen or lower alkyl; Y is ##STR4## R.sup.1 is hydrogen, lower alkyl or phenyl; R.sup.2 is hydrogen or lower alkyl; or R.sup.1 and R.sup.2 taken together form a benzene ring, optionally substituted by halo; R.sup.3 is --OR, ##STR5## or --NHSO.sub.2 R.sup.4 ; R.sup.4 is phenyl or loweralkyl substituted phenyl; and the pharmaceutically acceptable salts thereof, and their use in the treatment of leukotriene-mediated naso-bronchial obstructive airpassageway conditions, such as allergic rhinitis, allergic bronchial asthma and the like, in psoriasis, ulcerative colitis, rheumatoid arthritis as well as in other immediate hypersensitivity reactions.

  已披露的化合物的结构式如下：其中A是含有3-19个碳原子的烷基，低烷基烯丙基，二卤代烯丙基，二苯基烯丙基，低炔基，除了喹啉基外的其他结构；W是--CR.sub.2 O--, --CH.dbd.CH--或--CH.dbd.CHCH.sub.2 O--；X是N或CR；Z是--S--或--O--；R是氢或低烷基；Y是；R.sup.1是氢，低烷基或苯基；R.sup.2是氢或低烷基；或者R.sup.1和R.sup.2共同形成一个苯环，该苯环可以选择性地被卤素取代；R.sup.3是--OR，或--NHSO.sub.2 R.sup.4；R.sup.4是苯基或低烷基取代的苯基；以及它们的药用盐，以及它们在治疗白三烯介导的鼻支气管阻塞症状，如过敏性鼻炎，过敏性支气管哮喘等，牛皮癣，溃疡性结肠炎，类风湿性关节炎以及其他即时过敏反应中的用途。
• The geminal dimethyl analogue of Flurbiprofen as a novel Aβ42 inhibitor and potential Alzheimer’s disease modifying agent
  作者：Nicholas Stock、Benito Munoz、Jonathan D.J. Wrigley、Mark S. Shearman、Dirk Beher、James Peachey、Toni L. Williamson、Gretchen Bain、Weichao Chen、Xiaohui Jiang、René St-Jacques、Peppi Prasit

  DOI：10.1016/j.bmcl.2006.01.033

  日期：2006.4

  The subtle modification of a selection of A beta(42) inhibiting non-steroidal anti-inflammatory drugs (NSAIDs), through synthesis of the geminal dimethyl analogues, was anticipated to ablate their cyclooxygenase activity whilst maintaining A beta(42) inhibition. Methylflurbiprofen 6 exhibited similar in vitro A beta(42) inhibition to its parent NSAID Flurbiprofen and was further evaluated in the Tg2576 mouse model of Alzheimer's disease and an animal model of gastro-intestinal (GI) impairment, but proved unviable for further clinical development. (C) 2006 Elsevier Ltd. All rights reserved.