4-{2-[6-(3-amino-piopylamino)-pyrido [3,4-d] pyrimidin-4-ylamino]-phenoxy}-butyric acid ethyl ester | 855995-84-5

• 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: 4-{2-[6-(3-amino-piopylamino)-pyrido [3,4-d] pyrimidin-4-ylamino]-phenoxy}-butyric acid ethyl ester
• 英文别名: Ethyl 4-[2-[[6-(3-aminopropylamino)pyrido[3,4-d]pyrimidin-4-yl]amino]phenoxy]butanoate
• CAS: 855995-84-5
• 化学式: C₂₂H₂₈N₆O₃
• 分子量: 424.503
• InChiKey: KFAHVTZEWCFDPH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4-{2-[6-(3-amino-piopylamino)-pyrido [3,4-d] pyrimidin-4-ylamino]-phenoxy}-butyric acid ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 以100%的产率得到4-{2-[6-(3-amino-piopylamino)-pyrido [3,4-d] pyrimidin-4-ylamino]-phenoxy}-butyric acid
  参考文献：
  名称：

  [EN] PYRIDO- AND PYRIMIDOPYRIMIDINE DERIVATIVES AS ANTI- PROLIFERATIVE AGENTS
  [FR] ANTI-PROLIFERANTS A BASE DE DERIVES PYRIDO- ET PYRIMIDOPYRIMIDINE

  摘要：

  本发明涉及公式(I)的化合物，其N-氧化物形式，药学上可接受的加合盐及其立体化异构形式，其中a1-a2=a3-a4代表从N-CH=CH-CH，N-CH N-CH或CH-CH=N-CH中选择的二价基团；Z代表NH；Y代表-C3-9烷基-，-Cl-5烷基-NR13-Cl-5烷基-，-C1-6烷基-NH-CO-或-CO-NH -C1-6烷基-；X1代表-O-或-NR11-；X2代表-C1-2烷基-，-O-C1-2烷基，-O-或-O-CH2-；R1代表氢或卤素；R2代表氢，氰基，卤素，羟基甲酰-Cl-4烷氧基甲酰-，Het16-羰基或Ar5；R3代表氢；R4代表羟基，C1-4烷氧基-，Ar4-C1-4烷氧基或R4代表Cl-4烷氧基，其中一个或可能两个或更多取代基选择自C1-4烷氧基-或Het2-；R11代表氢；R12代表氢，Cl-4烷基-或Cl-4烷氧基甲酰-；R13代表Het14-Cl-4烷基，特别是吗啡啶基-Cl-4烷基；Het2代表选择自吗啡啶基或哌啶基的杂环，可选地取代为C1-4烷基-，最好是甲基；Het14代表吗啡啶基；Het16代表选择自吗啡啶基或吡咯啉基的杂环；Ar4代表苯基；Ar5代表苯基，可选地取代为氰基。

  公开号：

  WO2005058913A1
• 作为产物：
  描述：

  4-{2-[6-(3-tert-butoxycarbonylamino-piopylamino)-pyrido [3,4-d] pyrimidin-4-ylamino]-phenoxy}-butyric acid ethyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以100%的产率得到4-{2-[6-(3-amino-piopylamino)-pyrido [3,4-d] pyrimidin-4-ylamino]-phenoxy}-butyric acid ethyl ester
  参考文献：
  名称：

  [EN] PYRIDO- AND PYRIMIDOPYRIMIDINE DERIVATIVES AS ANTI- PROLIFERATIVE AGENTS
  [FR] ANTI-PROLIFERANTS A BASE DE DERIVES PYRIDO- ET PYRIMIDOPYRIMIDINE

  摘要：

  本发明涉及公式(I)的化合物，其N-氧化物形式，药学上可接受的加合盐及其立体化异构形式，其中a1-a2=a3-a4代表从N-CH=CH-CH，N-CH N-CH或CH-CH=N-CH中选择的二价基团；Z代表NH；Y代表-C3-9烷基-，-Cl-5烷基-NR13-Cl-5烷基-，-C1-6烷基-NH-CO-或-CO-NH -C1-6烷基-；X1代表-O-或-NR11-；X2代表-C1-2烷基-，-O-C1-2烷基，-O-或-O-CH2-；R1代表氢或卤素；R2代表氢，氰基，卤素，羟基甲酰-Cl-4烷氧基甲酰-，Het16-羰基或Ar5；R3代表氢；R4代表羟基，C1-4烷氧基-，Ar4-C1-4烷氧基或R4代表Cl-4烷氧基，其中一个或可能两个或更多取代基选择自C1-4烷氧基-或Het2-；R11代表氢；R12代表氢，Cl-4烷基-或Cl-4烷氧基甲酰-；R13代表Het14-Cl-4烷基，特别是吗啡啶基-Cl-4烷基；Het2代表选择自吗啡啶基或哌啶基的杂环，可选地取代为C1-4烷基-，最好是甲基；Het14代表吗啡啶基；Het16代表选择自吗啡啶基或吡咯啉基的杂环；Ar4代表苯基；Ar5代表苯基，可选地取代为氰基。

  公开号：

  WO2005058913A1

文献信息

• Pyrido-and pyrimidopyrimidine derivatives as anti-profilerative agents
  申请人：Freyne Jean Edgard Eddy

  公开号：US20070078132A1

  公开（公告）日：2007-04-05

  The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein a 1 -a 2 =a 3 -a 4 represents a divalent radical selected from N—CH═CH—CH, N—CH═N—CH or CH—CH═N—CH; Z represents NH; Y represents —C 3-9 alkyl-, —C 1-5 alkyl-NR 13 —C 1-5 alkyl-, —C 1-6 alkyl-NH—CO— or —CO—NH—C 1-6 alkyl-; X 1 represents —O— or —NR 11 —; X 2 represents —C 1-2 alkyl-, —O—C 1-2 alkyl, —O— or —O—CH 2 —; R 1 represents hydrogen or halo; R 2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C 1-4 alkyloxycarbonyl-, Het 16 -carbonyl- or Ar 5 ; R 3 represents hydrogen; R 4 represents hydroxy, C 1-4 alkyloxy-, Ar 4 —C 1-4 alkyloxy or R 4 represents C 1-4 alkyloxy substituted with one or where possible two or more substituents selected from C 1-4 alkyloxy- or Het 2 -; R 11 represents hydrogen; R 12 represents hydrogen, C 1-4 alkyl- or C 1-4 alkyl-oxy-carbonyl-; R 13 represents Het 14 -C 1-4 alkyl, in particular morpholinyl-C 1-4 alkyl; Het 2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C 1-4 alkyl-, preferably methyl; Het 14 represents morpholinyl; Het 16 represents a heterocycle selected from morpholinyl or pyrrolidinyl; Ar 4 represents phenyl; Ar 5 represents phenyl optionally substituted with cyano.
• PYRIDO-AND PYRIMIDOPYRIMIDINE DERIVATIVES AS ANTI-PROLIFERATIVE AGENTS
  申请人：Freyne Eddy Jean Edgard

  公开号：US20100173913A1

  公开（公告）日：2010-07-08

  The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein a 1 -a 2 =a 3 -a 4 represents a divalent radical selected from N—CH═CH—CH, N—CH═N—CH or CH—CH═N—CH; Z represents NH; Y represents —C 3-9 alkyl-, —C 1-5 alkyl-NR 13 —C 1-5 alkyl-, —C 1-6 alkyl-NH—CO— or —CO—NH—C 1-6 alkyl-; X 1 represents —O— or —NR 11 —; X 2 represents —C 1-2 alkyl-, —O—C 1-2 alkyl, —O— or —O—CH 2 —; R 1 represents hydrogen or halo; R 2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C 1-4 alkyloxycarbonyl-, Het 16 -carbonyl- or Ar 5 ; R 3 represents hydrogen; R 4 represents hydroxy, C 1-4 alkyloxy-, Ar 4 —C 1-4 alkyloxy or R 4 represents C 1-4 alkyloxy substituted with one or where possible two or more substituents selected from C 1-4 alkyloxy- or Het 2 -; R 11 represents hydrogen; R 12 represents hydrogen, C 1-4 alkyl- or C 1-4 alkyl-oxy-carbonyl-; R 13 represents Het 14 -C 1-4 alkyl, in particular morpholinyl-C 1-4 alkyl; Het 2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C 1-4 alkyl-, preferably methyl; Het 14 represents morpholinyl; Het 16 represents a heterocycle selected from morpholinyl or pyrrolidinyl; Ar 4 represents phenyl; Ar 5 represents phenyl optionally substituted with cyano.
• PYRIDO- AND PYRIMIDOPYRIMIDINE DERIVATIVES AS ANTI-PROFILERATIVE AGENTS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：US20130231353A1

  公开（公告）日：2013-09-05

  The present invention concerns the compounds of formula wherein a 1 -a 2 =a 3 -a 4 represents a divalent radical selected from N—CH═CH—CH, N—CH═N—CH or CH—CH═N—CH; Z represents NH; Y represents —C 3-9 alkyl-, —C 1-5 alkyl-NR 13 —C 1-5 alkyl-, —C 1-6 alkyl-NH—CO— or —CO—NH—C 1-6 alkyl-; X 1 represents —O— or —NR 11 —; X 2 represents —C 1-2 alkyl-, —O—C 1-2 alkyl, —O— or —O—CH 2 —; R 1 represents hydrogen or halo; R 2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C 1-4 alkyloxycarbonyl-, Het 16 -carbonyl- or Ar 5 ; R 3 represents hydrogen; R 4 represents hydroxy, C 1-4 alkyloxy-, Ar 4 —C 1-4 alkyloxy or substituted C 1-4 alkyloxy; R 11 represents hydrogen; R 12 represents hydrogen, C 1-4 alkyl- or C 1-4 alkyl-oxy-carbonyl-; R 13 represents morpholinyl-C 1-4 alkyl; Het 2 represents morpholinyl or piperidinyl optionally substituted with C 1-4 alkyl-, preferably methyl; Het 14 represents morpholinyl; Het 16 represents morpholinyl or pyrrolidinyl; Ar 4 represents phenyl; Ar 5 represents phenyl optionally substituted with cyano.
• US7799772B2
  申请人：——

  公开号：US7799772B2

  公开（公告）日：2010-09-21
• US8772272B2
  申请人：——

  公开号：US8772272B2

  公开（公告）日：2014-07-08