5-hydroxy-6-methoxy-2H-phthalazin-1-one | 228869-39-4

• 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: 5-hydroxy-6-methoxy-2H-phthalazin-1-one
• CAS: 228869-39-4
• 化学式: C₉H₈N₂O₃
• 分子量: 192.174
• InChiKey: HLAFJIQGDZUSDI-UHFFFAOYSA-N

物化性质

• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  70.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-hydroxy-6-methoxy-2H-phthalazin-1-one 在 sodium hydride 、 sodium carbonate 、 potassium iodide 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 1-(3,5-dichloropyridin-4-yl-methyl)-5-cyclopentyloxy-6-methoxy-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：

  3-苄氧基-4-甲氧基苯甲醛 在 吡啶 、 盐酸 、 氯化亚砜 、 Bu₄N⁺KMnO₄^- 、 仲丁基锂 、 一水合肼 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 28.08h， 生成 5-hydroxy-6-methoxy-2H-phthalazin-1-one
  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 phosphodiesterase 4 inhibitors
  申请人：Zambon Group S.p.A.

  公开号：US06329370B1

  公开（公告）日：2001-12-11

  The present invention provides a compound selected from the group including: 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-4-phenyl-phthalazine; 4-(3,5-dichloro-pyridin-4-ylmethyl)-7-methoxy-1H-phthalazin-2-carboxylic acid methyl ester; benzyl-{3-{1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazin-5-yl}-prop-2-ynyl}-methyl-amine; 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-5-(5-morpholin-4-yl-pent-1-ynyl)-phthalazine dihydrochloride; 3-{1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazin-5-yl}-prop-2-yn-1-ol; 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-4-morpholin-4-yl-phthalazine; 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-4-(1,2,4)triazol-1-yl-phthalazine; N→O derivatives thereof; and pharmaceutically acceptable salts thereof. The invention also provides a pharmaceutical composition which includes a therapeutically effective amount of the above compound in admixture with a suitable carrier.

  本发明提供了一种从以下组中选择的化合物：1-(3,5-二氯-吡啶-4-基甲基)-6-甲氧基-4-苯基-酞嗪；4-(3,5-二氯-吡啶-4-基甲基)-7-甲氧基-1H-酞嗪-2-羧酸甲酯；苄基-{3-{1-(3,5-二氯-吡啶-4-基甲基)-6-甲氧基-酞嗪-5-基}-丙-2-炔基}-甲基-胺；1-(3,5-二氯-吡啶-4-基甲基)-6-甲氧基-5-(5-吗啉-4-基-戊-1-炔基)-酞嗪二氢氯酸盐；3-{1-(3,5-二氯-吡啶-4-基甲基)-6-甲氧基-酞嗪-5-基}-丙-2-炔-1-醇；1-(3,5-二氯-吡啶-4-基甲基)-6-甲氧基-4-吗啉-4-基-酞嗪；1-(3,5-二氯-吡啶-4-基甲基)-6-甲氧基-4-(1,2,4)三唑-1-基-酞嗪；其N→O衍生物；及其药用可接受盐。本发明还提供了一种药物组合物，包括与适宜载体混合的上述化合物的治疗有效量。
• Phthalazine derivatives as phosphodiesterase 4 inhibitors
  申请人：Zambon Group S.p.A.

  公开号：US06589951B1

  公开（公告）日：2003-07-08

  Compounds of formula (I) wherein B is alkylene, amino, CONH or a bond; Cy is optionally substituted phenyl or heteroaryl; R is H, phenyl or (C1-4)alkyl optionally substituted; R1 is (C1-6)alkyl or polyfluoro(C1-6)-alkyl; R2 is (C4-7)cycloalkyl optionally containing an oxygen atom and optionally substituted; and the N→O derivatives and pharmaceutically acceptable salt thereof are PDE 4 and TNF&agr; inhibitors.

  式（I）中的化合物，其中B是烷基，氨基，CONH或键；Cy是可选择地取代的苯基或杂环芳基；R是H，苯基或（C1-4）烷基可选择地取代；R1是（C1-6）烷基或多氟（C1-6）-烷基；R2是（C4-7）环烷基，可选地含有一个氧原子并可选择地取代；它们的N→O衍生物及其药用可接受的盐是PDE 4和TNF&agr;抑制剂。
• [EN] PHTHALAZINE DERIVATIVES PHOSPHODIESTERASE 4 INHIBITORS<br/>[FR] DERIVES DE PHTALAZINE COMME INHIBITEURS DE PHOSPHODIESTERASE 4
  申请人：ZAMBON SPA

  公开号：WO2000005218A1

  公开（公告）日：2000-02-03

  Compounds of formula (I), wherein ------ is a single or double bond; Z is NH, methylene, a (C2-C6)alkylene chain optionally branched and/or unsaturated and/or interrupted by a (C5-C7)cycloalkyl residue; A is phenyl or heterocycle optionally substituted by one or more substituent(s) selected among oxo, nitro, carboxy groups and halogen atoms, or a COR4 group wherein R4 is hydroxy, (C1-C6)-alkoxy, amino optionally substituted by one or two (C1-C6)alkyl group(s) or by hydroxy; R is a (C1-C6)alkyl or polyfluoro(C1-C6)alkyl group; R1 is absent when ------ is a double bond or, when ------ is a single bond, is (a) hydrogen; (b) (C1-C6)alkyl optionally substituted by aryl, by heterocycle or by a COR5 group wherein R5 is hydroxy, (C1-C4)alkoxy or hydroxamino; (c) -COR6 wherein R6 is hydrogen, aryl, aryl-(C1-C6)alkyl, amino optionally alkylated or monohydroxylated, hydroxy, (C1-C4)alkoxy, carboxy, (C1-C4)alkoxycarbonyl, formula (1), or (C1-C4)alkyl optionally substituted by heterocycle; (d) (C1-C4)-alkylsulfonyl; R2 represents two hydrogen atoms or a group =O when ------ is a single bond, or, when ------ is a double bond, R2 is hydrogen, cyano, (C1-C4)alkoxycarbonyl, amido, optionally substituted aryl or heterocycle, (C1-C8)alkyl, (C2-C8)alkenyl or (C2-C8)alkynyl optionally branched and/or substituted by aryl or heterocycle; aryloxy, heterocyclyloxy, aryl-(C1-C4)alkoxy, heterocyclyl-(C1-C4) alkoxy, amino substituted by one or two (C1-C4)-alkyl group(s), arylamino, heterocyclylamino, aryl-(C1-C4)alkylamino, heterocyclyl-(C1-C4)-alkylamino; R3 is hydrogen, or a (C1-C8)alkyl, (C2-C8)alkenyl or (C2-C8)alkynyl group optionally substituted by hydroxy, oxo, aryl or heterocycle, and optionally interrupted by one or more heteroatom(s) or heterogroup(s); the N→O derivatives of the compounds of formula (I) and the pharmaceutically acceptable salts thereof are PDE 4 inhibitors.

  化合物的公式（I），其中------是单键或双键；Z是NH，亚甲基，（C2-C6）烷基链，可选地分支和/或不饱和和/或由（C5-C7）环烷基残基中断；A是苯基或杂环，可选地被氧代基，硝基，羧基和卤原子中的一个或多个取代基取代，或者是COR4基团，其中R4是羟基，（C1-C6）烷氧基，氨基，可选地被一种或两种（C1-C6）烷基基团或羟基取代；R是（C1-C6）烷基或聚氟（C1-C6）烷基团；当------是双键时，R1不存在；当------是单键时，R1是（a）氢；（b）（C1-C6）烷基，可选地被芳基，杂环或COR5基团取代，其中R5是羟基，（C1-C4）烷氧基或羟胺基；（c）-COR6，其中R6是氢，芳基，芳基-(C1-C6)烷基，氨基，可选地烷基化或单羟基化，羟基，（C1-C4）烷氧基，羧基，（C1-C4）烷氧基羰基，公式（1），或可选地被杂环取代的（C1-C4）烷基；（d）（C1-C4）烷基磺酰基；R2代表两个氢原子或一个=O基团，当------是单键时，或者当------是双键时，R2是氢，氰基，（C1-C4）烷氧基羰基，酰胺基，可选地被芳基或杂环取代，（C1-C8）烷基，（C2-C8）烯基或（C2-C8）炔基，可选地被芳基或杂环取代和/或分支；芳基氧基，杂环氧基，芳基-(C1-C4)烷氧基，杂环基-(C1-C4)烷氧基，氨基取代的一种或两种（C1-C4）烷基基团，芳基氨基，杂环基氨基，芳基-(C1-C4)烷基氨基，杂环基-(C1-C4)-烷基氨基；R3是氢，或者是（C1-C8）烷基，（C2-C8）烯基或（C2-C8）炔基，可选地被羟基，氧代基，芳基或杂环取代，并且可选地由一个或多个杂原子或杂基中断；公式（I）化合物的N→O衍生物及其药学上可接受的盐是PDE4抑制剂。
• Phthalazine derivatives as phosphodiesterase 4-inhibitors
  申请人：Zambon Group S.p.A

  公开号：US20040043999A1

  公开（公告）日：2004-03-04

  A process for preparing a compound of formula I: 1 wherein G is methylene, ethylene, CONH, amino or a bond; R is H, phenyl or a (C 1-4 )alkyl group optionally substituted by phenyl; Cy is phenyl or a 5- or 6-membered heterocycle of the group consisting of pyrrole, imidazole, pyrazole, pyrrolidine, pyrroline, imidazoline, imidazolidine, pyrazolidine, pyrazoline, pyridine, pyrazine, pyrimidine, pyridazine, piperazine, piperidine, and triazine, the Cy residue being optionally substituted by one or more substituent(s) selected from the group consisting of keto, nitro, carboxy, fluorine, chlorine, bromine, or iodine; R 1 is a (C 1-6 )alkyl or polyfluoro(C 1-6 )alkyl group; and R 2 is aryl, aryl-(C 1-10 )-alkyl, (C 4-7 )cycloalkyl or (C 4-7 )heterocycle wherein the heteroatom is an oxygen atom.

  一种制备化合物I的方法：其中，G为亚甲基，乙烯基，CONH，氨基或键；R为氢，苯基或(C1-4)烷基，可选地被苯基取代；Cy为苯基或由吡咯，咪唑，吡唑啉，吡咯烷，吡咯烷，咪唑啉，咪唑烷，吡唑烷，吡唑啉，吡啶，吡嗪，嘧啶，吡嗪，哌嗪，哌啶和三嗪组成的5-或6-成员杂环，Cy残基可选地被氧，硝基，羰基，氟，氯，溴或碘中的一个或多个取代基取代；R1为(C1-6)烷基或多氟(C1-6)烷基；R2为芳基，芳基-(C1-10)-烷基，(C4-7)环烷基或(C4-7)杂环，其中杂原子为氧原子。
• PHTHALAZINE DERIVATIVES PHOSPHODIESTERASE 4 INHIBITORS
  申请人：ZAMBON GROUP S.p.A.

  公开号：EP1042300A1

  公开（公告）日：2000-10-11