1-(2-bromo-4-pyridyl)-6,7-dimethoxy-2,3-bis(methoxycarbonyl)naphthalene | 186461-90-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 1-(2-bromo-4-pyridyl)-6,7-dimethoxy-2,3-bis(methoxycarbonyl)naphthalene
• 英文别名: 2,3-bis(methoxycarbonyl)-1-(2-bromo-4-pyridyl)-6,7-dimethoxynaphthalene；1-(2-bromo-4-pyridyl)-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthalene；1-(2-bromo-pyridin-4-yl)-2,3-bis(methoxycarbonyl)-6,7-dimethoxynaphthalene；dimethyl 1-(2-bromopyridin-4-yl)-6,7-dimethoxynaphthalene-2,3-dicarboxylate
• CAS: 186461-90-5
• 化学式: C₂₁H₁₈BrNO₆
• 分子量: 460.281
• InChiKey: LOPOFNPBGOUOAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  84
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(2-bromo-4-pyridyl)-6,7-dimethoxy-2,3-bis(methoxycarbonyl)naphthalene 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.0h， 以72%的产率得到2,3-bis(hydroxymethyl)-1-(2-bromo-4-pyridyl)-6,7-dimethoxynaphthalene
  参考文献：
  名称：

  Novel, Potent, and Selective Phosphodiesterase-4 Inhibitors as Antiasthmatic Agents:  Synthesis and Biological Activities of a Series of 1-Pyridylnaphthalene Derivatives

  摘要：

  The structural requirements for potent and selective PDE4 inhibition were revealed in a 1-pyridylnaphthalene series, and the best compound (3kg, T-2585 . HCl) was chosen for further biological evaluation (PDE4 inhibition IC50 = 0.13 nM, selectivity PDE3/4 ratio = 14 000). Compound 3kg showed potent antispasmogenic activities (ED50 = 0.063 mg/kg for reduction of antigen-induced bronchoconstriction, intravenously; ED50 = 0.033 mg/kg for reduction of histamine-induced bronchoconstriction, intraduodenally) in guinea pigs with little cardiovascular effects. Furthermore, 3kg induced significantly weaker emetic effects than RP73401 after oral administration in ferrets and intravenous administration in dogs (3kg, none of 4 ferrets vomited at a dose of 10 mg/kg, po and none of 8 dogs vomited at; a dose of 0.3 mg/kg, iv; RP73401, 4 of 8 ferrets vomited at a dose of 3 mg/kg, po and 6 of 8 dogs vomited at a dose of 0.3 mg/kg, iv); that is compatible with the lower affinity for the high-affinity rolipram binding site (3kg, 2.6 nM; RP73401, 0.85 nM). This may imply that 3kg has an improved therapeutic ratio because of a broad margin between the K-i value of binding affinity and the IC50 value of PDE4 inhibition (ratio = 0.050).

  DOI：

  10.1021/jm980314l
• 作为产物：
  描述：

  1-溴-2-(二甲氧基甲基)-4,5-二甲氧基苯 在 正丁基锂 、 三氟化硼乙醚 、 溶剂黄146 作用下， 以 乙腈 、 xylene 为溶剂， 反应 6.0h， 生成 1-(2-bromo-4-pyridyl)-6,7-dimethoxy-2,3-bis(methoxycarbonyl)naphthalene
  参考文献：
  名称：

  Novel, Potent, and Selective Phosphodiesterase-4 Inhibitors as Antiasthmatic Agents:  Synthesis and Biological Activities of a Series of 1-Pyridylnaphthalene Derivatives

  摘要：

  The structural requirements for potent and selective PDE4 inhibition were revealed in a 1-pyridylnaphthalene series, and the best compound (3kg, T-2585 . HCl) was chosen for further biological evaluation (PDE4 inhibition IC50 = 0.13 nM, selectivity PDE3/4 ratio = 14 000). Compound 3kg showed potent antispasmogenic activities (ED50 = 0.063 mg/kg for reduction of antigen-induced bronchoconstriction, intravenously; ED50 = 0.033 mg/kg for reduction of histamine-induced bronchoconstriction, intraduodenally) in guinea pigs with little cardiovascular effects. Furthermore, 3kg induced significantly weaker emetic effects than RP73401 after oral administration in ferrets and intravenous administration in dogs (3kg, none of 4 ferrets vomited at a dose of 10 mg/kg, po and none of 8 dogs vomited at; a dose of 0.3 mg/kg, iv; RP73401, 4 of 8 ferrets vomited at a dose of 3 mg/kg, po and 6 of 8 dogs vomited at a dose of 0.3 mg/kg, iv); that is compatible with the lower affinity for the high-affinity rolipram binding site (3kg, 2.6 nM; RP73401, 0.85 nM). This may imply that 3kg has an improved therapeutic ratio because of a broad margin between the K-i value of binding affinity and the IC50 value of PDE4 inhibition (ratio = 0.050).

  DOI：

  10.1021/jm980314l

文献信息

• Naphthalene derivatives, process for the preparation thereof, and
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US05969140A1

  公开（公告）日：1999-10-19

  Naphthalene derivatives of the formula [I]: ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and are each H, protected or unprotected OH, one of R.sup.3 and R.sup.4 is protected or unprotected hydroxymethyl, and the other is H, lower alkyl, or protected or unprotected hydroxymethyl, R.sup.5 and R.sup.6 are the same or different and are each H, substituted or unsubstituted lower alkyl, substituted or unsubstituted phenyl or protected or unprotected NH.sub.2, or both combine together with the adjacent N to form substituted or unsubstituted heterocyclic group, and pharmaceutically acceptable salts thereof, these compounds showing excellent bronchoconstriction inhibitory activity, and hence, being useful in the prophylaxis or treatment of asthma.

  萘衍生物的化学式[I]：其中R.sup.1和R.sup.2相同或不同，分别为H、保护或未保护的OH，R.sup.3和R.sup.4中的一个为保护或未保护的羟甲基，另一个为H、低碳烷基，或保护或未保护的羟甲基，R.sup.5和R.sup.6相同或不同，分别为H、取代或未取代的低碳烷基、取代或未取代的苯基或保护或未保护的NH.sub.2，或者两者与相邻的N结合形成取代或未取代的杂环基，以及其药学上可接受的盐，这些化合物表现出优异的支气管收缩抑制活性，因此在哮喘的预防或治疗中具有用处。
• A synthesis of 1-pyridylnaphthalene lignan analogs
  作者：Masakatsu Sugahara、Yasunori Moritani、Yoshihiro Terakawa、Tsuyoshi Ogiku、Tatsuzo Ukita、Tameo Iwasaki

  DOI：10.1016/s0040-4039(97)10849-8

  日期：1998.3

  A new series of 1-arylnaphthalene lignan analogs having a variety of pyridyl substituents at the C-1 position were synthesized in moderate to good yields by means of the Diels-Alder reaction by utilizing 1-pyridylisobenzofuran precursors with dimethyl fumarate, methyl acrylate, or dimethyl acetylene dicarboxylate, followed by BF3·Et2O-mediated aromatization.

  利用Diels-Alder反应，利用1-吡啶基异苯并呋喃前体与富马酸二甲酯，丙烯酸甲酯或乙炔二甲酸二甲酯，然后由BF 3 ·Et 2 O介导的芳构化。
• Naphthalene derivates, process for the preparation thereof, and intermediates therefor
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US06214996B1

  公开（公告）日：2001-04-10

  Naphthalene derivatives of the formula [I]: wherein R1 and R2 are the same or different and are each H, protected or unprotected OH, one of R3 and R4 is protected or unprotected hydroxymethyl, and the other is H, lower alkyl, or protected or unprotected hydroxymethyl, R5 and R6 are, the same or different and are each H, substituted or unsubstituted lower alkyl, substituted or unsubstituted phenyl or protected or unprotected NH2, or both combine together with the adjacent N to form substituted or unsubstituted heterocyclic group, and pharmaceutically acceptable salts thereof, these compounds showing excellent bronchoconstriction inhibitory activity, and hence, being useful in the prophylaxis or treatment of asthma.

  公式为 [I] 的萘衍生物：其中R1和R2相同或不同，分别为H、保护或未保护的OH，R3和R4中的一个为保护或未保护的羟甲基，另一个为H、低碳基或保护或未保护的羟甲基，R5和R6相同或不同，分别为H、取代或未取代的低碳基、取代或未取代的苯基或保护或未保护的NH2，或两者与相邻的N结合形成取代或未取代的杂环基，以及其药学上可接受的盐。这些化合物表现出良好的支气管收缩抑制活性，因此在哮喘的预防或治疗中有用。
• Method for Preparing Optically Active 4-Hydroxy-1,2,3,4-Tetrahydroquinoline Compound
  申请人：Okamoto Masaki

  公开号：US20090269821A1

  公开（公告）日：2009-10-29

  The present invention relates to a method for preparing an optically active 4-hydroxy-1,2,3,4-tetrahydroquinoline compound [I], which comprises the steps of: treating a racemic 4-hydroxy-1,2,3,4-tetrahydroquinoline compound represented by general formula [I]: [wherein R 1 represents a hydrogen atom or a protecting group for amino group.] with an enzyme having an ability of selectively or preferentially acylating one enantiomer of the racemic compound [I] in the presence of an acyl donor; and if necessary, subjecting the reaction product to solvolysis.

  本发明涉及一种制备光学活性的4-羟基-1,2,3,4-四氢喹啉化合物[I]的方法，其包括以下步骤：在酰基供体存在下，用具有选择性或优先酰化外消旋化合物[I]的一对映体的能力的酶处理由通式[I]表示的外消旋4-羟基-1,2,3,4-四氢喹啉化合物：[其中R1表示氢原子或氨基保护基]；如有必要，将反应产物进行溶剂解。
• Dermatitis treating agent
  申请人：Mitsubishi Tanabe Pharma Corporation

  公开号：US07868019B2

  公开（公告）日：2011-01-11

  The present invention is to provide a topical dermatitis treating agent which comprises a pyridine compound represented by the following formula [I]: wherein R1 and R2 each represent a lower alkoxy group, ═X— represents a group represented by the formula: or a group represented by the formula: ═N—, Ring A represents a saturated or unsaturated bicyclic nitrogen-containing heterocyclic group having 1 to 4 substituents selected from hydroxyl group, oxo group, a lower alkoxy group, a di-lower alkylaminophenyl group, a pyperidino-lower alkoxy group, a morpholino-lower alkoxy group, a cyclo-lower alkylamino-lower alkylamino group, pyridyl group and morpholino group, and represents a single bond or a double bond, or a pharmaceutically acceptable salt thereof as an active ingredient.

  本发明提供了一种局部治疗皮炎的药剂，其包含以下式[I]所表示的吡啶化合物，其中R1和R2各代表较低的烷氧基，═X—代表由以下式表示的基团：或由以下式表示的基团：═N—，环A代表具有1到4个取代基的饱和或不饱和的含氮杂环，所述取代基从羟基、氧代基、较低的烷氧基、二较低的烷基氨基苯基、吡哆啉较低的烷氧基、吗啉较低的烷氧基、环较低的烷基氨基较低的烷基氨基基、吡啶基和吗啉基中选择，并且表示单键或双键，或其药学上可接受的盐作为活性成分。