1-[2-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-oxo-ethyl]-1,3-dihydro-2H-imidazol-2-one | 183588-51-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[2-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-oxo-ethyl]-1,3-dihydro-2H-imidazol-2-one
• 英文别名: 1-[2-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-oxoethyl]-1,3-dihydro-2H-imidazol-2-one；1-[2-[3-(cyclopentyloxy)-4methoxyphenyl]-2-oxoethyl]-1,3-dihydro-2H-imidazol-2-one；1-[2-(3-Cyclopentyloxy-4-methoxy-phenyl)-2-oxo-ethyl]-1,3-dihydro-imidazol-2-one；3-[2-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxoethyl]-1H-imidazol-2-one
• CAS: 183588-51-4
• 化学式: C₁₇H₂₀N₂O₄
• 分子量: 316.357
• InChiKey: HGWZOWHNBASINH-UHFFFAOYSA-N

物化性质

• 密度：
  1.238±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[2-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-oxo-ethyl]-1,3-dihydro-2H-imidazol-2-one 在 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成
  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
• 作为产物：
  描述：

  3-环戊氧-4-甲氧基苯甲醛 在 镍 盐酸 、 草酰氯 、 氨 、 氢气 、 三乙胺 、 zinc(II) iodide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 生成 1-[2-[3-(cyclopentyloxy)-4-methoxyphenyl]-2-oxo-ethyl]-1,3-dihydro-2H-imidazol-2-one
  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

• 1,3-dihydro-1-(phenylalkenyl)-2H-imidazol-2-one derivatives having PDE
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US05952510A1

  公开（公告）日：1999-09-14

  The present invention concerns the compounds of formula ##STR1## the N-oxide forms, the pharmaceutically acceptable acid or base addition salts and the stereochemically isomeric forms thereof, wherein R.sup.1 and R.sup.2 each independently are hydrogen; C.sub.1-6 alkyl; difluoromethyl; trifluoromethyl; C.sub.3-6 cycloalkyl; a saturated 5-, 6 or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; bicyclo\x9b2.2.1!-2-heptenyl; bicyclo\x9b2.2.1!heptanyl; C.sub.1-6 alkylsulfonyl; arylsulfonyl; or substituted C.sub.1-10 alkyl; R.sup.3 is hydrogen, halo or C.sub.1-6 alkyloxy; R.sup.4 is hydrogen; cyano; optionally substituted C.sub.1-6 alkyl; C.sub.1-6 alkyloxycarbonyl or aryl; R.sup.5 is hydrogen; cyano; optionally substituted C.sub.1-6 alkyl; C.sub.1-6 alkyloxycarbonyl or aryl; Y is a direct bond or C.sub.1-3 alkanediyl; --A--B-- is a bivalent radical of formula --CR.sup.6 .dbd.CR.sup.7 -- or --CHR.sup.6 --CHR.sup.7 --; L is hydrogen; optionally substituted C.sub.1-6 alkyl; C.sub.1-6 alkylcarbonyl; C.sub.1-6 alkyloxycarbonyl; C.sub.1-6 alkylsulfonyl or arylsulfonyl; aryl is optionally substituted phenyl; Het is morpholinyl or optionally substituted piperidinyl, -piperazinyl, -pyridinyl;, -furanyl or -thienyl; having PDE IV and cytokine inhibiting activity. Further, pharmaceutical compositions, preparations and use as a medicine are described.

  本发明涉及以下结构的化合物##STR1##其N-氧化物形式，药学上可接受的酸或碱盐及其立体化异构体形式，其中R.sup.1和R.sup.2各自独立地为氢；C.sub.1-6烷基；二氟甲基；三氟甲基；C.sub.3-6环烷基；含有一个或两个氧、硫或氮等异原子的饱和5、6或7元杂环；吲哚基；双环\x9b2.2.1!-2-庚烯基；双环\x9b2.2.1!-庚烷基；C.sub.1-6烷基磺酰基；芳基磺酰基；或取代的C.sub.1-10烷基；R.sup.3为氢、卤素或C.sub.1-6烷氧基；R.sup.4为氢；氰基；可选择取代的C.sub.1-6烷基；C.sub.1-6烷氧羰基或芳基；R.sup.5为氢；氰基；可选择取代的C.sub.1-6烷基；C.sub.1-6烷氧羰基或芳基；Y为直接键或C.sub.1-3烷二基；--A--B--为式--CR.sup.6 .dbd.CR.sup.7 --或--CHR.sup.6 --CHR.sup.7 --的二价基团；L为氢；可选择取代的C.sub.1-6烷基；C.sub.1-6烷基羰基；C.sub.1-6烷氧羰基；C.sub.1-6烷基磺酰基或芳基磺酰基；芳基为可选择取代的苯基；Het为吗啉基或可选择取代的哌啶基、-哌嗪基、-吡啶基、-呋喃基或-噻吩基；具有PDE IV和细胞因子抑制活性。此外，还描述了药物组合物、制剂和用作药物的用途。
• 1,3-dihydro-2H-imidazol-2-one compounds
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05869515A1

  公开（公告）日：1999-02-09

  The present invention concerns the compounds of formula ##STR1## the N-oxide forms, the pharmaceutically acceptable acid or base addition salts and the stereochemically isomeric forms thereof, wherein R.sup.1 and R.sup.2 each independently are hydrogen; C.sub.1-6 alkyl; difluoromethyl; trifluoromethyl; C.sub.3-6 cycloalkyl; a saturated 5-, 6- or 7-membered heterocycle containing one or two heteroatoms selected from oxygen, sulfur or nitrogen; indanyl; bicyclo\x9b2.2.1!-2-heptenyl; bicyclo\x9b2.2.1!heptanyl; C.sub.1-6 alkylsulfonyl; arylsulfonyl; or substituted C.sub.1-10 alkyl; R3 is hydrogen, halo or C.sub.1-6 alkyloxy ##STR2## is a bivalent radical of formula ##STR3## Alk is C1-4alkanediyl; --A--B-- is a bivalent radical of formula: --CR.sup.6 .dbd.CR.sup.7 -- or --CHR.sup.6 --CHR.sup.7 --; L is hydrogen; optionally substituted C.sub.1-6 alkyl; C.sub.1-6 alkylcarbonyl; C.sub.1-6 alkyloxycarbonyl; optionally substituted C.sub.3-6 alkenyl; optionally substituted piperidinyl; C.sub.1-6 alkylsulfonyl or arylsulfonyl; aryl is optionally substituted phenyl; Het.sup.1 is morpholinyl or optionally substituted pyridinyl, -furanyl, -thienyl, -hydroxypyridinyl, -imidazolyl, -thiazolyl, -oxazolyl, -isoquinolinyl, -quinolinonyl, -piperidinyl, -piperazinyl; and Het.sup.2 is morpholinyl or optionally substituted piperidinyl, -piperazinyl, -pyridinyl, -furanyl or -thienyl; having PDE IV and cytokine inhibiting activity. The invention also relates to processes for preparing the compounds of formula (I) and pharmaceutical compositions thereof.

  本发明涉及公式##STR1##的化合物，其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，其中R.sup.1和R.sup.2各自独立地为氢; C.sub.1-6烷基; 二氟甲基; 三氟甲基; C.sub.3-6环烷基; 一个含有氧，硫或氮中的一个或两个杂原子的饱和的5-，6-或7-成员杂环; 印丹基; 双环\x9b2.2.1!-2-庚烯基; 双环\x9b2.2.1!庚基; C.sub.1-6烷基磺酰基; 芳基磺酰基; 或取代的C.sub.1-10烷基; R3为氢，卤素或C.sub.1-6烷氧基；##STR2##是公式##STR3##的二价基团；Alk为C1-4烷基二亚甲基；--A--B--是公式：--CR.sup.6 .dbd.CR.sup.7 --或--CHR.sup.6 --CHR.sup.7 --的二价基团；L为氢；可选取代的C.sub.1-6烷基；C.sub.1-6烷基羰基；C.sub.1-6烷氧羰基；可选取代的C.sub.3-6烯基；可选取代的哌啶基；C.sub.1-6烷基磺酰基或芳基磺酰基；芳基为可选取代的苯基；Het.sup.1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，-氧唑基，-异喹啉基，-喹啉基，-哌啶基，-哌嗪基; Het.sup.2是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；具有PDE IV和细胞因子抑制活性。本发明还涉及制备公式（I）化合物及其药物组合物的过程。
• 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-; - - -O- - -; - - -N（R8）- - -; 或- -CH=CH- -; 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 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-酮类化合物及其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以及/或与生理上有害的细胞因子过多有关的疾病状态，特别是过敏性、特应性和炎症性疾病的温血动物。
• 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。