5-methoxy-4-[(tetrahydro-3-furanyl)oxy]-2-pyridinecarboxaldehyde | 244629-41-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-methoxy-4-[(tetrahydro-3-furanyl)oxy]-2-pyridinecarboxaldehyde
• 英文别名: 5-Methoxy-4-(oxolan-3-yloxy)pyridine-2-carbaldehyde
• CAS: 244629-41-2
• 化学式: C₁₁H₁₃NO₄
• 分子量: 223.229
• InChiKey: RZVOGWQTTXJDAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  57.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-methoxy-4-[(tetrahydro-3-furanyl)oxy]-2-pyridinecarboxaldehyde 、 三甲基氰硅烷 在 zinc(II) iodide 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以100%的产率得到(+/-)-5-methoxy-4-[(tetrahydro-3-furanyl)oxy]-α-[(trimethylsilyl) oxy]-2-pyridineacetonitrile
  参考文献：
  名称：

  PDE IV inhibiting pyridine derivatives

  摘要：

  本发明涉及具有以下式的吡啶衍生物的N-氧化物形式，其药学上可接受的加合物盐和其立体化学异构体形式，其中L为氢；C1-6烷基；C1-6烷基羰基；C1-6烷氧羰基；取代的C1-6烷基；C3-6烯基；取代的C3-6烯基；哌啶基；取代的哌啶基；C1-6烷基磺酰基或芳基磺酰基；—A—B—为—CR8═CR5—或—CHR4—CHR5—；D为O或NR6；R1为氢或C1-4烷基；R2为氢；卤素；C1-6烷基；三氟甲基；C3-6环烷基；羧基；C1-4烷氧羰基；C3-6环烷基氨基羰基；芳基；Het1；或取代的C1-6烷基；或R2为—O—R9或—NH—R10；R3为氢，卤素，羟基，C1-6烷基或C1-6烷氧基；或R2和R1，或R2和R3一起可以形成二价基团；Q为二取代的吡啶；R7和R8各自独立地为氢；C1-6烷基；二氟甲基；三氟甲基；C3-6环烷基；含有一个或两个氧、硫或氮的饱和的5、6或7元杂环；茚基；6,7-二氢-5H-环戊吡啶基；双环[2.2.1]-2-庚烯基；双环[2.2.1]庚基；C1-6烷基磺酰基；芳基磺酰基；或取代的C1-10烷基；具有PDE IV和细胞因子抑制活性。本发明还涉及制备式(I)化合物的方法，其制药组成物以及其作为药物的用途。

  公开号：

  US06656959B1

文献信息

• PDE IV INHIBITING PYRIDINE DERIVATIVES
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1068194B1

  公开（公告）日：2003-11-05
• US6656959B1
  申请人：——

  公开号：US6656959B1

  公开（公告）日：2003-12-02
• [EN] PDE IV INHIBITING PYRIDINE DERIVATIVES<br/>[FR] DERIVES DE PYRIDINE INHIBITEURS DE PDE IV
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1999050262A1

  公开（公告）日：1999-10-07

  (EN) The present invention concerns pyridine derivatives having formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein L is hydrogen; C1-6alkyl; C1-6alkyl carbonyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl; C3-6alkenyl; substituted C3-6alkenyl; piperidyl; substituted piperidyl; C1-6alkylsulfonyl or arylsulfonyl; -A-B- is -CR4=CR5- or -CHR4-CHR5-; D is O or NR6; R1 is a hydrogen or C1-4alkyl; R2 is hydrogen; halo; C1-6alkyl; trifluoromethyl; C3-6cycloalkyl; carboxyl; C1-4alkyl oxycarbonyl; C3-6cycloalkylaminocarbonyl; aryl; HET1; or substituted C1-6alkyl; or R2 is O-R9 or NH-R10; R3 is hydrogen, halo, hydroxy, C1-6alkyl or C1-6alkyloxy; or R2 and R1, or R2 and R3 taken together may form a bivalent radical; Q is disubstituted pyridine; R7 and R8 each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cyclo alkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; 6,7-dihydro-5H-cyclopentapyridyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C1-10alkyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I), pharmaceutical compositions thereof and their use as a medicament.(FR) Cette invention se rapporte à des dérivés de pyridine représentés par la formule (I), aux formes N-oxyde, aux sels d'addition acceptables sur le plan pharmaceutique et aux formes stéréochimiquement isomères de ces composés, formule dans laquelle L représente hydrogène; C1-6alkyle; C1-6alkyle carbonyle; C1-6alkyloxycarbonyle; C1-6alkyle substitué; C3-6alcényle; C3-6alcényle substitué; pipéridyle; pipéridyle substitué; C1-6alkylsulfonyle ou arylsulfonyle; -A-B- représente -CR4=CR5- ou -CHR4-CHR5-; D représente O ou NR6; R1 représente hydrogène ou C1-4alkyle; R2 représente hydrogène; halo; C1-6alkyle; trifluorométhyle; C3-6cycloalkyle; carboxyle; C1-4alkyloxycarbonyle; C3-6cycloalkylaminocarbonyle; aryle; Het1; ou C1-6alkyle substitué; ou R2 représente -O-R9 ou -NH-R10; R3 représente hydrogène, halo, hydroxy, C1-6alkyle ou C1-6alkyloxy; ou R2 et R1, ou R2 et R3 ensemble peuvent former un radical bivalent; Q représente pyridine disubstitué; R7 et R8 représentent chacun séparément hydrogène; C1-6alkyle; difluorométhyle; trifluorométhyle; C3-6cycloalkyle; un hétérocycle à 5, 6 ou 7 éléments saturé contenant un ou deux hétéroatomes choisis parmi oxygène, soufre ou azote; indanyle; 6,7-dihydro-5H-cyclopentrapyridyle; bicyclo[2.2.1]-2-heptényle; bicyclo[2.2.1]heptanyle; C1-6 alkylesulfonyle; arylsulfonyle; ou C1-10alkyle substitué. Ces composés ont un pouvoir d'inhibition de la PDE IV (phosphodiestérase IV) et de la cytokine. Cette invention se rapporte également à des procédés de préparation des composés de la formule (I), à des compositions pharmaceutiques de ces composés et à leur utilisation comme médicament.
• PDE IV inhibiting pyridine derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：US06656959B1

  公开（公告）日：2003-12-02

  The present invention concerns pyridine derivatives having the formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein L is hydrogen; C1-6alkyl; C1-6alkyl carbonyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl; C3-6alkenyl; substituted C3-6alkenyl; piperidyl; substituted piperidyl; C1-6alkylsulfonyl or arylsulfonyl; —A—B— is —CR8═CR5— or—CHR4—CHR5—; D is O or NR6; R1 is a hydrogen or C1-4alkyl; R2 is hydrogen; halo; C1-6alkyl; trifluoromethyl; C3-6cycloalkyl; carboxyl; C1-4alkyl oxycarbonyl; C3-6cycloalkylaminocarbonyl; aryl; Het1; or substituted C1-6alkyl; or R2 is —O—R9 or —NH—R10; R3 is hydrogen, halo, hydroxy, C1-6alkyl or C1-6alkyloxy; or R2 and R1, or R2 and R3 taken together may form a bivalent radical; Q is disubstituted pyridine; R7 and R8 each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cyclo alkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; 6,7-dihydro-5H-cyclopentapyridyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C1-10alkyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I), pharmaceutical compositions thereof and their use as a medicament.

  本发明涉及具有以下式的吡啶衍生物的N-氧化物形式，其药学上可接受的加合物盐和其立体化学异构体形式，其中L为氢；C1-6烷基；C1-6烷基羰基；C1-6烷氧羰基；取代的C1-6烷基；C3-6烯基；取代的C3-6烯基；哌啶基；取代的哌啶基；C1-6烷基磺酰基或芳基磺酰基；—A—B—为—CR8═CR5—或—CHR4—CHR5—；D为O或NR6；R1为氢或C1-4烷基；R2为氢；卤素；C1-6烷基；三氟甲基；C3-6环烷基；羧基；C1-4烷氧羰基；C3-6环烷基氨基羰基；芳基；Het1；或取代的C1-6烷基；或R2为—O—R9或—NH—R10；R3为氢，卤素，羟基，C1-6烷基或C1-6烷氧基；或R2和R1，或R2和R3一起可以形成二价基团；Q为二取代的吡啶；R7和R8各自独立地为氢；C1-6烷基；二氟甲基；三氟甲基；C3-6环烷基；含有一个或两个氧、硫或氮的饱和的5、6或7元杂环；茚基；6,7-二氢-5H-环戊吡啶基；双环[2.2.1]-2-庚烯基；双环[2.2.1]庚基；C1-6烷基磺酰基；芳基磺酰基；或取代的C1-10烷基；具有PDE IV和细胞因子抑制活性。本发明还涉及制备式(I)化合物的方法，其制药组成物以及其作为药物的用途。