3-(6-Methoxy-naphthalen-2-yl)-propionyl chloride | 114318-43-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-(6-Methoxy-naphthalen-2-yl)-propionyl chloride
• 英文别名: 3-(6-Methoxynaphthalen-2-yl)propanoyl chloride
• CAS: 114318-43-3
• 化学式: C₁₄H₁₃ClO₂
• 分子量: 248.709
• InChiKey: POYVLGKVWFALGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(6-Methoxy-naphthalen-2-yl)-propionyl chloride 在 sodium azide 、 三氟化硼乙醚 作用下， 反应 16.0h， 生成 3,4-Dihydro-8-methoxybenz[h]isoquinolin-1(2H)-one
  参考文献：
  名称：

  Examination of the Role of the Acidic Hydrogen in Imparting Selectivity of 7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) Toward Inhibition of Phenylethanolamine N-Methyltransferase vs the α₂-Adrenoceptor^1a

  摘要：

  7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661, 1) is a potent inhibitor of the enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), In contrast to other inhibitors of PNMT, it is also highly selective toward PNMT in comparison with its affinity toward the alpha(2)-adrenoceptor (PNMT K-i = 0.55 mu M, alpha(2) K-i = 100 mu M, selectivity [alpha(2) K-i/PNMT K-i] = 180). A diverse set of compounds was synthesized and evaluated to probe the role of the acidic hydrogen of the aminosulfonyl group of 1 in imparting this selectivity. Compounds were designed to investigate the effect on selectivity of the acidity of the NH group [the 7-N-methyl (compound 5) and 7-N-(p-chlorophenyl) (compound 4) derivatives of 1], the relative spatial position of the acidic hydrogen [7-(N-(methylsulfonyl)amino)-1,2,3,4-tetrahydroisoquinoline (6) and 7-((N-(methylsulfonyl)amino)methyl)-1,2,3,4-tetrahydroisoquinoline (8)], or the effect of the substitution of an acidic phenolic group for the aminosulfonyl moiety [1-(aminomethyl)-6-hydroxynaphthalene (23) and 8-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline (9)]. All of the compounds studied displayed lower affinity for PNMT than I, and nine of the eleven compounds studied showed increased, rather than the desired decreased, affinity for the alpha(2)-adrenoceptor. Specifically, compound 4, in which the aminosulfonyl NH group is more acidic than that in 1, showed greatly reduced selectivity on account of increased alpha(2)-adrenoceptor affinity as compared to 1 (PNMT K-i = 2.6 mu M, alpha(2) K-i = 6.3 mu M, selectivity = 2.4). Compound 8, in which the acidic NH group is in the same region of space as that in 1, although the aminosulfonyl group is reversed with respect to the aromatic ring, showed poor PNMT affinity and modest alpha(2)-adrenoceptor affinity (PNMT K-i = 330 mu M, alpha(2) K-i = 18 mu M, selectivity = 0.055). Compound 9, in which a phenolic group is in the same region of space as the acidic NH of 1, exhibited the best alpha(2)-adrenoceptor affinity of any of the compounds studied (PNMT K-i = 0.98 mu M, alpha(2) K-i = 0.078 mu M, selectivity = 0.080). Results from this study suggest that the selectivity of 1 is not solely due to the presence of an acidic hydrogen on the 7-aminosulfonyl group of 1 but is likely also dependent on some other property (e.g.electron-withdrawing character) of the aminosulfonyl group.

  DOI：

  10.1021/jm960235e
• 作为产物：
  描述：

  3-(6-methoxynaphthalen-2-yl)propanoic acid 在 草酰氯 作用下， 反应 2.0h， 生成 3-(6-Methoxy-naphthalen-2-yl)-propionyl chloride
  参考文献：
  名称：

  Examination of the Role of the Acidic Hydrogen in Imparting Selectivity of 7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661) Toward Inhibition of Phenylethanolamine N-Methyltransferase vs the α₂-Adrenoceptor^1a

  摘要：

  7-(Aminosulfonyl)-1,2,3,4-tetrahydroisoquinoline (SK&F 29661, 1) is a potent inhibitor of the enzyme phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), In contrast to other inhibitors of PNMT, it is also highly selective toward PNMT in comparison with its affinity toward the alpha(2)-adrenoceptor (PNMT K-i = 0.55 mu M, alpha(2) K-i = 100 mu M, selectivity [alpha(2) K-i/PNMT K-i] = 180). A diverse set of compounds was synthesized and evaluated to probe the role of the acidic hydrogen of the aminosulfonyl group of 1 in imparting this selectivity. Compounds were designed to investigate the effect on selectivity of the acidity of the NH group [the 7-N-methyl (compound 5) and 7-N-(p-chlorophenyl) (compound 4) derivatives of 1], the relative spatial position of the acidic hydrogen [7-(N-(methylsulfonyl)amino)-1,2,3,4-tetrahydroisoquinoline (6) and 7-((N-(methylsulfonyl)amino)methyl)-1,2,3,4-tetrahydroisoquinoline (8)], or the effect of the substitution of an acidic phenolic group for the aminosulfonyl moiety [1-(aminomethyl)-6-hydroxynaphthalene (23) and 8-hydroxy-1,2,3,4-tetrahydrobenz[h]isoquinoline (9)]. All of the compounds studied displayed lower affinity for PNMT than I, and nine of the eleven compounds studied showed increased, rather than the desired decreased, affinity for the alpha(2)-adrenoceptor. Specifically, compound 4, in which the aminosulfonyl NH group is more acidic than that in 1, showed greatly reduced selectivity on account of increased alpha(2)-adrenoceptor affinity as compared to 1 (PNMT K-i = 2.6 mu M, alpha(2) K-i = 6.3 mu M, selectivity = 2.4). Compound 8, in which the acidic NH group is in the same region of space as that in 1, although the aminosulfonyl group is reversed with respect to the aromatic ring, showed poor PNMT affinity and modest alpha(2)-adrenoceptor affinity (PNMT K-i = 330 mu M, alpha(2) K-i = 18 mu M, selectivity = 0.055). Compound 9, in which a phenolic group is in the same region of space as the acidic NH of 1, exhibited the best alpha(2)-adrenoceptor affinity of any of the compounds studied (PNMT K-i = 0.98 mu M, alpha(2) K-i = 0.078 mu M, selectivity = 0.080). Results from this study suggest that the selectivity of 1 is not solely due to the presence of an acidic hydrogen on the 7-aminosulfonyl group of 1 but is likely also dependent on some other property (e.g.electron-withdrawing character) of the aminosulfonyl group.

  DOI：

  10.1021/jm960235e

文献信息

• [EN] PROCESS FOR PREPARING NITROOXYDERIVATIVES OF NAPROXEN<br/>[FR] PROCEDE DE PREPARATION DE DERIVES NITROOXY DU NAPROXENE
  申请人：NICOX SA

  公开号：WO2004020384A1

  公开（公告）日：2004-03-11

  The present invention refers to a process for preparing a compound of general formula (A), wherein R is a radical of naproxen or bromonaproxen and R1-R12 are hydrogen or alkyl groups, m, n, o, q, r and s are each independently an integer from 0 to 6, and p is 0 or 1, and X is O, S, SO, SO2, NR13 or PR13 or an aryl, heteroaryl group, said process comprising reacting a compound of formula (B) : R-COOZ wherein R is as defined above and Z is hydrogen or a cation selected from: Li+, Na+, K+, Ca++, Mg++, tetralkylammonium, tetralkylphosphonium, with a compound of formula (C), as reported in the description, wherein R1-R12 and m, n, o, p, q, r, s are as defined above and Y is a suitable leaving group.

  本发明涉及一种制备通式（A）化合物的方法，其中R是萘普洛芬或溴萘普洛芬的基团，R1-R12为氢或烷基，m、n、o、q、r和s分别独立地为0到6的整数，p为0或1，X为O、S、SO、SO2、NR13或PR13或芳基、杂环芳基团，所述方法包括将通式（B）化合物：R-COOZ其中R如上定义，Z为氢或从Li+、Na+、K+、Ca++、Mg++、四烷基铵、四烷基磷酸盐中选择的阳离子，与通式（C）化合物反应，如描述中所述，其中R1-R12和m、n、o、p、q、r、s如上定义，Y为适当的脱离基团。
• Optcally active compounds
  申请人：SANYO CHEMICAL INDUSTRIES LTD.

  公开号：EP0385692A2

  公开（公告）日：1990-09-05

  Optically active compounds represented by the following formula (1), (2) or (3) are disclosed. wherein R and R are C1-20 alkyl groups; X and Y1 are -, O, S, or divalent groups such as COO, OOC and OCOO; m is 0 or 1; n is 0 to 5; A2 is a cyclic group, such as p,p'-biphenylene, 2,6-naphthylene, 2,5-pyrimidinylene-1,4-phenylene, A1-Y2-pyridylene or A4-Y2-A5; Y2 is CH2CH2 or C-C triple bond; A3 is 2,6-naphthylene, A1-Y2-pyridylene or A6-CH2CH2-A7; A1, A4, As, A6 and A7 are cyclic groups, such as 1,4-phenylene and/or 4,4 -biphenylene.

  本发明公开了下式（1）、（2）或（3）所代表的光学活性化合物。 其中 R 和 R 是 C1-20 烷基；X 和 Y1 是-、O、S 或二价基团，如 COO、OOC 和 OCOO；m 是 0 或 1；n 是 0 至 5；A2 是环状基团，如 p,p'-联苯、2,6-萘、2,5-嘧啶-1,4-亚苯基、A1-Y2-吡啶或 A4-Y2-A5；Y2 是 CH2CH2 或 C-C 三键；A3 是 2，6-萘、A1-Y2-吡啶或 A6-CH2CH2-A7；A1、A4、As、A6 和 A7 是环状基团，如 1，4-亚苯基和/或 4，4-联苯。
• PROCESS FOR PREPARING NITROOXYDERIVATIVES OF NAPROXEN
  申请人：NicOx S.A.

  公开号：EP1532098A1

  公开（公告）日：2005-05-25
• US4605659A
  申请人：——

  公开号：US4605659A

  公开（公告）日：1986-08-12
• US4704392A
  申请人：——

  公开号：US4704392A

  公开（公告）日：1987-11-03