3,4-dimethoxy-6-(2-bromo-4-pyridyl)(hydroxy)methylbenzaldehyde dimethylacetal | 186461-76-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3,4-dimethoxy-6-(2-bromo-4-pyridyl)(hydroxy)methylbenzaldehyde dimethylacetal
• 英文别名: (2-Bromopyridin-4-yl)-[2-(dimethoxymethyl)-4,5-dimethoxyphenyl]methanol；(2-bromopyridin-4-yl)-[2-(dimethoxymethyl)-4,5-dimethoxyphenyl]methanol
• CAS: 186461-76-7
• 化学式: C₁₇H₂₀BrNO₅
• 分子量: 398.254
• InChiKey: BLINJKFCKGIHPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,4-dimethoxy-6-(2-bromo-4-pyridyl)(hydroxy)methylbenzaldehyde dimethylacetal 在 sodium tetrahydroborate 、 三氟化硼乙醚 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 、 xylene 为溶剂， 反应 7.0h， 生成 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：

  6-溴藜芦醛 在 正丁基锂 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 4.5h， 生成 3,4-dimethoxy-6-(2-bromo-4-pyridyl)(hydroxy)methylbenzaldehyde dimethylacetal
  参考文献：
  名称：

  PROCESS FOR PRODUCTION OF OPTICALLY ACTIVE 4-HYDROXY-1,2,3,4 -TETRAHYDROQUINOLINES

  摘要：

  公开号：

  EP1964925B1

文献信息

• 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。
• METHOD FOR PRODUCING OPTICALLY ACTIVE NAPHTHALENE COMPOUND
  申请人：Matsuyama Koji

  公开号：US20150152082A1

  公开（公告）日：2015-06-04

  The present invention provides an industrially advantageous method for producing an optically active naphthalene compound useful as a therapeutic agent for dermatitis or the like. Specifically, the present invention provides a method for producing an optically active naphthalene compound [I], which comprises: a step of reacting a compound [a-1] and a compound [b-1] with each other in the presence of a base and a catalyst that is composed of a Pd compound and a tertiary phosphine ligand (step a); a step of asymmetrically hydrogenating a compound [c-1] in the presence of a hydrogen donor and a complex that is prepared from a ruthenium compound and a chiral ligand, or alternatively in the presence of an optically active oxazaborolidine compound (a CBS catalyst) and a boron hydride compound (step b); and a step of treating a compound [d-1] with a reducing agent (step c). (In the above formulae, R a and R b represent the same or different lower alkyl groups; and X 1 represents a halogen atom.)

  本发明提供了一种在工业上具有优势的方法，用于生产一种光学活性萘化合物，该化合物可用作治疗皮炎或类似疾病的治疗剂。具体而言，本发明提供了一种生产光学活性萘化合物[I]的方法，包括以下步骤：在碱和由Pd化合物和三级膦配体组成的催化剂存在下，将化合物[a-1]和化合物[b-1]彼此反应（步骤a）；在氢供体和由钌化合物和手性配体制备的配合物或者在光学活性氧杂硼烷化合物（CBS催化剂）和硼氢化合物存在下，对化合物[c-1]进行不对称氢化（步骤b）；以及用还原剂处理化合物[d-1]（步骤c）。 （在上述公式中，Ra和Rb表示相同或不同的低碳基团；X1表示卤素原子。）
• WO2007/40240
  申请人：——

  公开号：——

  公开（公告）日：——
• 1-Arylnaphthalene Lignan:  A Novel Scaffold for Type 5 Phosphodiesterase Inhibitor
  作者：Tatsuzo Ukita、Yoshinori Nakamura、Akira Kubo、Yasuo Yamamoto、Masami Takahashi、Jun Kotera、Tomohiro Ikeo

  DOI：10.1021/jm9807048

  日期：1999.4.1

  1-Arylnaphthalene lignan, which had been reported as a PDE4 inhibitor by Iwasaki, was disclosed as a new structural class of PDE5 inhibitors. The structural requirements for potent and specific PDE5 inhibition were revealed in a 1-arylnaphthalene lignan series, in which 1-(3-bromo-4, 5-dimethoxyphenyl)-5-chloro-3-[4-(2-hydroxyethyl)-1-piperazinylcarbonyl]-2-(methoxycarbonyl)naphthalene hydrochloride (27q) showed the most potent and specific inhibition (PDE5 inhibition IC50 = 6.2 nM, selectivity for PDE5 against PDE1, -2, -3, and -4 > 16 000). It is noteworthy that 27q has the best selectivities against PDE isoforms among PDE5 inhibitors so far reported. Compound 27q exhibited almost the same relaxant effects on rat aortic rings as sodium 1-[6-chloro-4-[(3,4-methylenedioxybenzyl)amino]quinazolin-2-yl]piperidine-4-carboxylate (35) (27q, EC50 = 0.10 mu M; 35, EC50 = 0.20 mu M) and was selected for further biological evaluation.
• US9181217B2
  申请人：——

  公开号：US9181217B2

  公开（公告）日：2015-11-10