3-(cyclopropylmethoxy)-4-methoxybenzeneacetonitrile | 153200-65-8

• 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-(cyclopropylmethoxy)-4-methoxybenzeneacetonitrile
• 英文别名: (3-cyclopropylmethoxy-4-methoxyphenyl)acetonitrile；2-[3-(cyclopropylmethoxy)-4-methoxyphenyl]acetonitrile
• CAS: 153200-65-8
• 化学式: C₁₃H₁₅NO₂
• 分子量: 217.268
• InChiKey: ODQLPZDHEUHLAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(cyclopropylmethoxy)-4-methoxybenzeneacetonitrile 在 sodium hydroxide 、 茴香硫醚 、 potassium carbonate 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4-(3-cyclopropylmethoxy-4-methoxyphenyl)-4-cyanopiperidin-1-yl)acetic acid
  参考文献：
  名称：

  Highly potent PDE4 inhibitors with therapeutic potential

  摘要：

  Based on the hypothesis that the dose-limiting side effects of PDE4 inhibitors could be mediated via the central nervous system (CNS), design and synthesis of a hydrophilic analogue is considered to be one approach to improving the side-effect profile of Ariflo(TM) 1. Water-soluble piperidine derivatives were found to possess therapeutic potential. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.087
• 作为产物：
  描述：

  (3-(Cyclopropylmethoxy)-4-methoxyphenyl)methanol 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.0h， 生成 3-(cyclopropylmethoxy)-4-methoxybenzeneacetonitrile
  参考文献：
  名称：

  咪唑-2-酮和2-氰基氨基咪唑衍生物的合成和生物学评估：新系列的PDE4抑制剂。

  摘要：

  该交流描述了一系列新的咪唑-2-酮和2-氰基氨基咪唑衍生物的合成和体外PDE4抑制活性。还在体内模型中测试了所描述的化合物，以评估其局部给药后的抗炎活性以及胃肠道副作用。几种化合物被证明是有效的PDE4抑制剂，某些2-氰基氨基咪唑类药物与参考化合物相比，胃肠道副作用较小，但局部给药后仍具有抗炎活性。

  DOI：

  10.1016/s0960-894x(01)00817-4

文献信息

• Compounds useful for treating allergic or inflammatory diseases
  申请人：SmithKline Beecham Corporation

  公开号：US05449686A1

  公开（公告）日：1995-09-12

  Novel cyclohexanes of Formulas (I) and (II) ##STR1## are described herein. They inhibit the production of Tumor Necrosis Factor and are useful in the treatment of disease states mediated or exacerbated by TNF production; these compounds are also useful in the mediation or inhibition of enzymatic or catalytic activity of phosphodiesterase V.

  本文描述了化学式（I）和（II）的新型环己烷化合物。它们抑制肿瘤坏死因子的产生，并可用于治疗由TNF产生介导或加重的疾病状态；这些化合物还可用于介导或抑制磷酸二酯酶V的酶活性。
• 1,3-dihydro-1-(phenylalkyl)-2H-imidazol-2-one compounds and their use
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US05994376A1

  公开（公告）日：1999-11-30

  The present invention describes 1,3-dihydro-1-(phenylalkyl)-2H-imidazol-2-one compounds and their use for treating warm-blooded animals suffering from disease states related to an abnormal enzymatic or catalytic activity of phosphodiesterase IV (PDE IV), and/or disease states related to a physiologically detrimental excess of cytokines, in particular allergic, atopic and inflammatory diseases.

  本发明描述了1,3-二氢-1-(苯基烷基)-2H-咪唑-2-酮化合物及其用于治疗患有与磷酸二酯酶IV（PDE IV）的异常酶活性或催化活性相关的疾病状态，以及与生理上有害的细胞因子过量相关的疾病状态，特别是过敏、特应性和炎症性疾病的温血动物。
• [EN] PDE IV INHIBITING 2-CYANOIMINOIMIDAZOLE DERIVATIVES<br/>[FR] DERIVES DE 2-CYANOIMINOIMIDAZOLE INHIBANT LA PHOSPHODIESTERASE IV
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1998014432A1

  公开（公告）日：1998-04-09

  (EN) The present invention concerns 2-cyanoiminoimidazole derivatives having formula (I) the $i(N)-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein R1 and R2 each independently are hydrogen; C1-6alkyl; difluoromethyl; trifluoromethyl; C3-6cycloalkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; 6,7-dihydro-5$i(H)-cyclopentapyridinyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C1-6alkylsulfonyl; arylsulfonyl; or substituted C1-10alkyl; R3 is hydrogen, halo or C1-6alkyloxy; R4 is hydrogen; halo; C1-6alkyl; trifluoromethyl; C3-6cycloalkyl; carboxyl; C1-4alkyloxycarbonyl; C3-6cycloalkylaminocarbonyl; aryl; Het1; or substituted C1-6alkyl; or R4 is -O-R7 or -NH-R8; R5 is hydrogen, halo, hydroxy, C1-6alkyl or C1-6alkyloxy; R6 is a hydrogen or C1-4alkyl; or R4 and R6, or R4 and R5 taken together may form a bivalent radical; -A-B- is -CR10=CR11- or -CHR10-CHR11-; L is hydrogen; C1-6alkyl; C1-6alkylcarbonyl; C1-6alkyloxycarbonyl; substituted C1-6alkyl; C3-6alkenyl; substituted C3-6alkenyl; piperidinyl; substituted piperidinyl; C1-6alkylsulfonyl or arylsulfonyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I) and pharmaceutical compositions thereof.(FR) L'invention concerne des dérivés de 2-cyanoiminoimidazole présentant la formule (I), les formes de $i(N)-oxyde, les sels d'addition pharmaceutiquement acceptables et les formes stéréochimiquement isomériques de ces derniers. Dans la formule, R1 et R2 sont chacun indépendamment de l'hydrogène, de l'alkyle C1-6, difluorométhyle, trifluorométhyle, cycloalkyle C3-6; un hétérocycle saturé à 5 ou 6 éléments contenant un ou deux hétéroatomes sélectionnés parmi de l'oxygène, du soufre ou de l'azote; indanyle; 6,7-dihydro-5$i(H)-cyclopentapyridinyle; bicyclo(2.2.1)-2-heptényle; bicyclo(2.2.1.)heptanyle; alkylsulfonyle C1-6; arylsulfonyle, ou de l'alkyle C1-10 substitué. R3 représente hydrogène, halo ou alkyloxy C1-6; R4 représente hydrogène, halo; alkyle C1-6, trifluorométhyle, cycloalkyle C3-6, carboxyle, alkyloxycarbonyle C1-4, cycloalkyle C3-6 aminocarbonyle; aryle; Het1, ou alkyle C1-6 substitué; ou R4 est -O-R7 ou -NH-R8. R5 est hydrogène, halo, hydroxy, alkyle C1-6 ou alkyloxy C1-6. R6 est un hydrogène ou un alkyle C1-4 ou R4 et R6, ou R4 et R5 pris ensemble forment un radical bivalent. -A-B- est -CR10=CR11- ou -CHR10-CHR11-; L est hydrogène, alkyle C1-6, alkylcarbonyle C1-6; alkyloxycarbonyle C1-6; alkyle C1-6 substitué, alkényle C3-6, alkényle C3-6 substitué, pipéridinyle, pipéridinyle substitué, alkylsulfonyle C1-6 ou arylsulfonyle, présentant une activité inhibant la cytokine et la phosphodiesterase IV. L'invention concerne aussi des procédés de préparation des composés de la formule (I) et des compositions pharmaceutiques de ces derniers.

  本发明涉及具有式(I)的2-氰基亚咪唑衍生物，它们的$i(N)-氧化物形式，药学上可接受的加成盐和其立体化学异构体，其中R1和R2各自独立地为氢; C1-6烷基; 二氟甲基; 三氟甲基; C3-6环烷基; 包含一个或两个从氧、硫或氮中选择的杂原子的饱和的5、6或7元杂环; indanyl; 6,7-二氢-5$i(H)-环戊吡啶基; bicyclo[2.2.1]-2-庚烯基; bicyclo[2.2.1]庚烷基; C1-6烷基磺酰基; 芳基磺酰基; 或取代的C1-10烷基; R3为氢、卤素或C1-6烷氧基; R4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R4为-O-R7或-NH-R8; R5为氢、卤素、羟基、C1-6烷基或C1-6烷氧基; R6为氢或C1-4烷基; 或R4和R6，或R4和R5共同形成一个双价基团; -A-B-为-CR10=CR11-或-CHR10-CHR11-; 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; 具有PDE IV和细胞因子抑制活性的制剂。本发明还涉及制备式(I)化合物和其制药组合物的方法。
• 1,3-DIHYDRO-1-(PHENYLALKYL)-2H-IMIDAZOL-2-ONE DERIVATIVES
  申请人：——

  公开号：US20020068830A1

  公开（公告）日：2002-06-06

  The present invention describes the use of compounds for the manufacture of a medicament for treating warm-blooded animals suffering from disease states related to an abnormal enzymatic or catalytic activity of phosphodiesterase IV (PDE IV), and/or disease states related to a physiologically detrimental excess of cytokines, in particular allergic, atopic and inflammatory diseases, said compounds having the formula 1 the N-oxide forms, the pharmaceutically acceptable acid or base addition salts and the stereochemically isomeric forms thereof, wherein R 1 and R 2 each independently are hydrogen; C 1-6 alkyl; difluoromethyl; trifluoromethyl; C 3-6 cycloalkyl; a saturated 5-, 6 or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; bicyclo[2.2.1]-2-heptenyl; bicyclo[2.2.1]heptanyl; C 1-6 alkylsulfonyl; arylsulfonyl; or substituted C 1-10 alkyl; R 3 is hydrogen, halo or C 1-6 alkyloxy; R 4 is hydrogen; halo; optionally substituted C 1-6 alkyl; trifluoromethyl; C 3-6 cycloalkyl; carboxyl; C 1-4 alkyloxycarbonyl; C 3-6 cycloalkylaminocarbonyl; aryl; Het 1 ; or R 4 is a radical of formula: —O—R 6 ; or —NH—R 7 ; R 5 is hydrogen, halo, hydroxy or C 1-6 alkyl; or R 4 and R 5 taken together may form a bivalent radical of formula: —(CH 2 ) n —; —CH 2 —CH 2 —O—CH 2 —CH 2 —; —CH 2 —CH 2 —N(R 8 )—CH 2 —CH 2 —; or —CH 2 —CH═CH—CH 2 —; Y is a direct bond, haloC 1-4 alkanediyl or C 1-4 alkanediyl; —A—B— is a bivalent radical of formula: —CR 9 ═CR 10 —; or —CHR 9 —CHR 10 —; and L is hydrogen; optionally substituted C 1-6 alkyl; C 1-6 alkylcarbonyl; C 1-6 alkyloxycarbonyl; optionally substituted C 3-6 alkenyl; optionally substituted piperidinyl; C 1-6 alkylsulfonyl or arylsulfonyl; aryl is optionally substituted phenyl; Het 1 is morpholinyl or optionally substituted pyridinyl, -furanyl, -thienyl, -hydroxypyridinyl, -imidazolyl, -thiazolyl, -oxazolyl, -isoquinolinyl, -quinolinonyl, -piperidinyl, or -piperazinyl ; Het 2 is morpholinyl or optionally substituted piperidinyl;, -piperazinyl, -pyridinyl, -furanyl or -thienyl. The present invention also relates to new compounds having PDE IV and cytokine inhibiting activity, processes for their preparation and compositions comprising said new compounds.

  本发明描述了使用化合物制备药物，用于治疗患有与磷酸二酯酶IV（PDE IV）的异常酶促或催化活性相关的疾病状态和/或与细胞因子生理有害过量相关的疾病状态，特别是过敏性，特应性和炎症性疾病。这些化合物的公式为1，其中包括N-氧化物形式，药学上可接受的酸或碱加成盐和立体化学异构体形式。其中，R1和R2各自独立地为氢; C1-6烷基; 二氟甲基; 三氟甲基; C3-6环烷基; 饱和的5-,6或7元杂环，其中包含一个或两个从氧，硫或氮中选择的杂原子; 印丹基; 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; R3为氢，卤素或C1-6烷氧基; R4为氢，卤素; 可选的取代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R4为式的基团：-O-R6; 或-NH-R7; R5为氢，卤素，羟基或C1-6烷基; 或R4和R5一起可以形成式的双价基团：-(CH2)n-; -CH2-CH2-O-CH2-CH2-; -CH2-CH2-N（R8）-CH2-CH2-; 或-CH2-CH=CH-CH2-; Y为直接键，卤素C1-4烷二基或C1-4烷二基; -A-B-为式的双价基团：-CR9=CR10-; 或-CHR9-CHR10-; L为氢; 可选的取代C1-6烷基; C1-6烷基羰基; C1-6烷氧羰基; 可选的取代C3-6烯基; 可选的取代哌啶基; C1-6烷基磺酰基或芳基磺酰基; 芳基为可选的取代苯基; Het1为吗啉基或可选取代的吡啶基，-呋喃基，-噻吩基，-羟基吡啶基，-咪唑基，-噻唑基，-噁唑基，-异喹啉基，-喹啉基，-哌啶基或-哌嗪基; Het2为吗啉基或可选取代的哌啶基，-哌嗪基，-吡啶基，-呋喃基或-噻吩基。本发明还涉及具有PDE IV和细胞因子抑制活性的新化合物，以及制备这些新化合物的方法和包含这些新化合物的组合物。
• 1,3-dihydro-1-(phenylalkyl)-2H-imidazol-2-one derivatves
  申请人：Janssen Pharmaceutica N.V.

  公开号：US06403805B1

  公开（公告）日：2002-06-11

  The present invention describes compounds useful for treating warm-blooded animals suffering from disease states related to an abnormal enzymatic or catalytic activity of phosphodiesterase IV (PDE IV), and/or disease states related to a physiologically detrimental excess of cytokines, in particular allergic, atopic and inflammatory diseases, said compounds having the formula the N-oxide forms, the pharmaceutically acceptable acid or base addition salts and the stereochemically isomeric forms thereof.

  本发明描述了对治疗患有与磷酸二酯酶IV（PDE IV）的异常酶活性或催化活性相关的疾病状态以及/或与生理上有害的细胞因子过量相关的疾病状态，特别是过敏、特应性和炎症性疾病的恒温动物有用的化合物，所述化合物具有N-氧化物形式、药学上可接受的酸或碱盐和其立体化学异构体形式的公式。