1-chloro-5-cyclopentyloxy-6-methoxy-2H-phthalazine | 1027966-28-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-chloro-5-cyclopentyloxy-6-methoxy-2H-phthalazine
• 英文别名: 1-chloro-5-cyclopentyloxy-6-methoxy-phthalazine；1-chloro-5-cyclopentyloxy-6-methoxyphthalazine
• CAS: 1027966-28-4
• 化学式: C₁₄H₁₅ClN₂O₂
• 分子量: 278.738
• InChiKey: GYKJQVOISLTTLX-UHFFFAOYSA-N

物化性质

• 沸点：
  469.5±40.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-chloro-5-cyclopentyloxy-6-methoxy-2H-phthalazine 在 sodium p-thiocresolate 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 5-Cyclopentyloxy-1-(3,5-dichloropyridin-4-yl-methyl)-6-hydroxy-phthalazine
  参考文献：
  名称：

  The synthesis and biological evaluation of a novel series of phthalazine PDE4 inhibitors I

  摘要：

  This communication describes the synthesis and in vitro evaluation of a novel and potent series of phosphodiesterase type IV (PDE4) inhibitors. The compounds described represent conformationally constrained analogues of RP 73401, Piclamilast. Preliminary evidences of reduced side effects of 11 compared to standards are also reported. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00449-2
• 作为产物：
  描述：

  4-甲氧基-3-苯基甲氧基苯甲酰氯 在 盐酸 、 仲丁基锂 、 sodium carbonate 、 一水合肼 、 溶剂黄146 、 potassium iodide 、 三氯氧磷 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， 反应 40.08h， 生成 1-chloro-5-cyclopentyloxy-6-methoxy-2H-phthalazine
  参考文献：
  名称：

  The synthesis and biological evaluation of a novel series of phthalazine PDE4 inhibitors I

  摘要：

  This communication describes the synthesis and in vitro evaluation of a novel and potent series of phosphodiesterase type IV (PDE4) inhibitors. The compounds described represent conformationally constrained analogues of RP 73401, Piclamilast. Preliminary evidences of reduced side effects of 11 compared to standards are also reported. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00449-2

文献信息

• Phthalazine derivatives as phosphodiesterase 4 inhibitors
  申请人：Zambon Group S.p.A.

  公开号：US06340684B1

  公开（公告）日：2002-01-22

  The present invention provides a compound selected from the group including: N-3-acetyl-1-(3,5-dichloropyridin-4-ylmethyl)-5-cyclopentyloxy-6-methoxy-4H-phthalazine; 6,7-dimethoxy-1-pyridin-4-ylmethyl-4-thiazol-2-yl-phthalazine; 1-(6,7-dimethoxy-4-pyridin-4-ylmethyl-1H-phthalazin-2-yl)ethanone; 2-methanesulphonyl-6,7-dimethoxy-4-pyridin-4-ylmethyl-1,2-dihydrophthalazine; 2-formyl-6,7-dimethoxy-4-pyridin-4-ylmethyl-1,2-dihydrophthalazine; 1-(6,7-dimethoxy-4-pyridin-4-ylmethyl-1H-phthalazin-2-yl)-1-imidazol-1-ylmethanone; 1-(3,5-dichloro-pyridin-4-ylmethyl)-3-methansulphonyl-6-difluoromethoxy-5-(tetrahydro-furan-2-yloxy)-4H-phthalazine; N→O derivatives thereof; and pharmaceutically acceptable salts thereof. The invention also provides a pharmaceutical composition, which contains a therapeutically effective amount of the above compound in admixture with a pharmaceutically acceptable carrier.

  本发明提供了一种从以下组中选择的化合物：N-3-乙酰基-1-(3,5-二氯吡啶-4-基甲基)-5-环戊氧基-6-甲氧基-4H-邻苯二嗪；6,7-二甲氧基-1-吡啶-4-基甲基-4-噻唑-2-基-邻苯二嗪；1-(6,7-二甲氧基-4-吡啶-4-基甲基-1H-邻苯二嗪-2-基)乙酮；2-甲磺酰基-6,7-二甲氧基-4-吡啶-4-基甲基-1,2-二氢邻苯二嗪；2-甲酰基-6,7-二甲氧基-4-吡啶-4-基甲基-1,2-二氢邻苯二嗪；1-(6,7-二甲氧基-4-吡啶-4-基甲基-1H-邻苯二嗪-2-基)-1-咪唑-1-基甲酮；1-(3,5-二氯吡啶-4-基甲基)-3-甲磺酰基-6-二氟甲氧基-5-(四氢呋喃-2-氧基)-4H-邻苯二嗪；以及其N→O衍生物和其药学上可接受的盐。本发明还提供了一种药物组合物，其含有上述化合物的治疗有效量与药学上可接受的载体混合。
• PHTHALAZINE DERIVATIVES AS PHOSPHODIESTERASE 4 INHIBITORS
  申请人：ZAMBON GROUP S.p.A.

  公开号：EP1098886A1

  公开（公告）日：2001-05-16
• US6340684B1
  申请人：——

  公开号：US6340684B1

  公开（公告）日：2002-01-22
• US6498160B2
  申请人：——

  公开号：US6498160B2

  公开（公告）日：2002-12-24
• [EN] PHTHALAZINE DERIVATIVES AS PHOSPHODIESTERASE 4 INHIBITORS<br/>[FR] DERIVES PHTALAZINE UTILISES EN TANT QU'INHIBITEURS DE PHOSPHODIESTERASES 4
  申请人：ZAMBON SPA

  公开号：WO2000005219A1

  公开（公告）日：2000-02-03

  Compounds of formula (I) wherein B is NH, methylene, a C2-6 alkylene chain optionally branched and/or unsaturated and/or interrupted by a C5-7 cycloalkyl residue; A is phenyl or heterocycle optionally substituted; R represents two hydrogen atoms or a C=O group when ----- is a single bond or, when ----- is a double bond, is hydrogen, optionally substituted aryl or heterocycle, (C1-8)-alkyl, (C2-8)-alkenyl or (C2-8)-alkynyl optionally substituted by aryl or heterocycle; aryloxy, heterocyclyloxy, aryl-C1-4-alkoxy, heterocyclyl-C1-4-alkoxy, amino substituted by 1 or 2 C1-4-alkyl group(s), aryl-amino, heterocyclyl-amino, aryl-C1-4-alkylamino, heterocyclyl-C1-4-alkylamino; R1 is a C1-6-alkyl, aryl, aryl-C1-10-alkyl, C4-7-cycloalkyl group optionally containing an oxygen atom and/or substituted; R2 is a C1-6-alkyl, polyfluoroC1-6-alkyl group; R3, when ----- is a single bond, is (a) hydrogen; (b) C1-6-alkyl optionally substituted by aryl, by heterocycle or by a COR5 group wherein R5 is hydroxy, C1-4-alkoxy or hydroxyamino; (c) -COR6 wherein R6 is hydrogen, aryl, aryl-C1-6-alkyl, amino optionally alkylated or monohydroxylated, hydroxy, C1-4-alkoxy, carboxy, C1-4-alkoxycarbonyl, formula (II) or C1-4-alkyl optionally substituted by heterocycle; (d) C1-4 alkyl-sulfonyl; the N→O derivatives of the compounds of formula (I) and the pharmaceutically acceptable salts thereof; are PDE 4 inhibitors.