6,7-dimethoxy-4-(pyridin-4-yl-methyl)-2H-phthalazin-1-one | 228869-58-7

• 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: 6,7-dimethoxy-4-(pyridin-4-yl-methyl)-2H-phthalazin-1-one
• 英文别名: 6,7-dimethoxy-4-(pyridin-4-ylmethyl)-2H-phthalazin-1-one
• CAS: 228869-58-7
• 化学式: C₁₆H₁₅N₃O₃
• 分子量: 297.313
• InChiKey: LWZZUMIGUJADKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-4-(pyridin-4-yl-methyl)-2H-phthalazin-1-one 在 POBr₃ 作用下， 以 甲醇 、 氢氧化钾 、 二氯甲烷 、 乙腈 为溶剂， 以31%的产率得到1-bromo-6,7-dimethoxy-4-pyridin-4-ylmethyl-phthalazine
  参考文献：
  名称：

  Phthalazine derivatives as phosphodiesterase 4 inhibitors

  摘要：

  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。

  公开号：

  US06589951B1
• 作为产物：
  描述：

  5,6-dimethoxy-3-pyridin-4-ylmethylene-3H-isobenzofuran-1-one 在 一水合肼 作用下， 以87%的产率得到6,7-dimethoxy-4-(pyridin-4-yl-methyl)-2H-phthalazin-1-one
  参考文献：
  名称：

  Tricyclic phthalazine derivatives as phosphodiesterase 4 inhibitors

  摘要：

  公式(I)中的三环邻苯二酮化合物，其中A是含有1至4个氮原子的5-7元杂环，可部分或完全不饱和，并且可被(C1-4)烷基基团取代，该基团也可被取代；Z是NH、亚甲基、一个C2-6烷基链，可分支和/或不饱和和/或被C5-7环烷基残基打断；Cy是苯基或杂环，可被一个或多个取代基取代，或者是一个COR4基团，其中R4是羟基、烷氧基、氨基，可被一到两个(C1-6)烷基基团或羟基取代；R是一个(C1-6)烷基或多氟化(C1-6)烷基基团；R1是氢原子；一个(C1-8)烷基、(C2-8)烯基或(C2-8)炔基，可由羟基、氧代、芳基或杂环取代，并且可被一个或多个杂原子或杂基打断；一个(C1-4)烷氧基或一个(C4-7)环烷氧基，可含有一个氧原子，并且可被环中的极性取代基取代，芳氧基芳基-(C1-10)-烷氧基；其N-O衍生物和药用盐已被描述。公式(I)中的化合物是PDE 4抑制剂。

  公开号：

  US06525055B1

文献信息

• [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：EP1371648A1

  公开（公告）日：2003-12-17

  Compounds of formula 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, 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.

  式中的化合物 其中 ----- 是单键或双键；Z 是 NH、亚甲基、任选支化和/或不饱和和/或被(C5-C7)环烷基残基打断的(C2-C6)亚烷基链；A 是苯基或杂环，任选被选自氧代、硝基、羧基和卤素原子中的一个或多个取代基或 COR4 基团取代，其中 R4 是羟基、(C1-C6)-烷氧基、任选被一个或两个(C1-C6)烷基取代的氨基或羟基；R 是(C1-C6)烷基或多氟(C1-C6)烷基；当 ----- 为双键时，R1 不存在，或当 ----- 为单键时，R1 是 (a) 氢；(b) 可选择被芳基、杂环或 COR5 基团取代的(C1-C6)烷基，其中 R5 是羟基、(C1-C4)烷氧基或羟基氨基；(c)-COR6 其中 R6 是氢、芳基、芳基-(C1-C6)烷基、任选被烷基化或单羟基 化的氨基、羟基、(C1-C4)烷氧基、羧基、(C1-C4)烷氧羰基、 (d) (C1-C4)-烷基磺酰基；当 ----- 为单键时，R2 代表两个氢原子或一个基团 =O；当 ----- 为双键时，R2 代表氢、氰基、(C1-C4)烷氧基羰基、氨基、任选取代的芳基或杂环、任选支化和/或被芳基或杂环取代的 (C1-C8)烷基、(C2-C8)烯基或(C2-C8)炔基；芳氧基、杂环氧基、芳基-(C1-C4)烷氧基、杂环-(C1-C4)烷氧基、被一个或两个 (C1-C4)- 烷基取代的氨基、芳基氨基、杂环氨基、芳基-(C1-C4)烷基氨基、杂环-(C1-C4)-烷基氨基；式 I 化合物的 N→O 衍生物及其药学上可接受的盐类是 PDE 4 抑制剂。
• 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
• PHTHALAZINE DERIVATIVES USEFUL AS PHOSPHODIESTERASE 4 INHIBITORS
  申请人：ZAMBON GROUP S.p.A.

  公开号：EP1042300B1

  公开（公告）日：2004-02-11