4-(4-Aminophenyl)piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester | 412332-09-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 4-(4-Aminophenyl)piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester
• 英文别名: 9H-fluoren-9-ylmethyl 4-(4-aminophenyl)piperidine-1-carboxylate
• CAS: 412332-09-3
• 化学式: C₂₆H₂₆N₂O₂
• 分子量: 398.505
• InChiKey: GAQUKPNQMAZESO-UHFFFAOYSA-N

物化性质

• 沸点：
  601.4±55.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-Aminophenyl)piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.33h， 生成
  参考文献：
  名称：

  ST7612AA1, a Thioacetate-ω(γ-lactam carboxamide) Derivative Selected from a Novel Generation of Oral HDAC Inhibitors

  摘要：

  A systematic study of medicinal chemistry aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group (ZBG) and of an amide-lactam in the ?-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new class of potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, and efficient synthetic approaches were used to synthesize a library of these new derivatives, which were then submitted to a screening for HDAC inhibition as well as to a preliminary in vitro assessment of their antiproliferative activity. Molecular docking into HDAC crystal structures suggested a binding mode for these thiol derivatives consistent with the stereoselectivity observed upon insertion of amide-lactam substituents in the ?-position. ST7612AA1 (117), selected as a drug candidate for further development, showed an in vitro activity in the nanomolar range associated with a remarkable in vivo antitumor activity, highly competitive with the most potent HDAC inhibitors, currently under clinical trials. A preliminary study of PK and metabolism is also illustrated.

  DOI：

  10.1021/jm5008209
• 作为产物：
  描述：

  4-(4-Nitrophenyl)piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester 在 5%-palladium/activated carbon 盐酸 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 6.0h， 以85%的产率得到4-(4-Aminophenyl)piperidine-1-carboxylic acid 9H-fluoren-9-ylmethyl ester
  参考文献：
  名称：

  Novel aminophenyl piperazine or aminophenyl piperidine derivatives inhibiting prenyl transferase proteins and method for preparing same

  摘要：

  该发明涉及与一般式（I）相对应的化合物，其中，特别是：W代表氢，COR6，CSR6，SO2R6，CO（CH2）nR6，（CH2）nR7；X代表CH或N；Y代表（CH2）n，CO，CH2CO，CH═CHCO，CH2CH2CO；Z代表杂环。当Z=吡啶时，Y不是CO。R1代表氢，C1-C6烷基，卤素OCH3，CF3；R2和R3，相同或不同，代表氢，C1-C6烷基；R4代表a）氢，b）C1-C6烷基，c）芳基，d）杂环；R5代表氢，COR7R8，SO2R7，CO（CH2）nSR7，CO（CH2）nOR7，CONR7R8，CO（CH2）mCOR7；R6代表a）苯基或萘基，b）C1-C6烷基，环烷基，c）杂环，d）NR7R8；R7和R8，相同或不同，代表a）氢，C1-C15烷基，b）杂环，c）芳基；n表示0到10；m表示2到10；前提是当Z代表喹唑啉或苯并咪唑基团时，R5不是CH2Ph或甲基，n不是零。

  公开号：

  US20040092524A1

文献信息

• DERIVES D'AMINOPHENYLE PIPERAZINE OU D'AMINO PHENYLE PIPERIDINE INHIBITEURS DE PROTEINES PRENYL TRANSFERASE
  申请人：PIERRE FABRE MEDICAMENT

  公开号：EP1324999A1

  公开（公告）日：2003-07-09
• [EN] NOVEL AMINOPHENYL PIPERAZINE OR AMINOPHENYL PIPERIDINE DERIVATIVES INHIBITING PRENYL TRANSFERASE PROTEINS AND METHODS FOR PREPARING SAME<br/>[FR] DERIVES D'AMINOPHENYLE PIPERAZINE OU D'AMINO PHENYLE PIPERIDINE INHIBITEURS DE PROTEINES PRENYL TRANSFERASE
  申请人：PF MEDICAMENT

  公开号：WO2002030927A1

  公开（公告）日：2002-04-18

  L'invention concerne des composés répondant à la formule générale (I), dans laquelle notamment : W représente : hydrogène, COR6, CSR6, SO2R6, CO(CH2)nR6, (CH2)nR7 ; X représente : CH ou N ; Y représente : (CH2)n, CO, CH2CO, CH=CHCO, CH2CH2CO ; Z représente un hétérocycle. Quand Z = pyridine alors Y est différent de CO. R1 représente : Hydrogène, C1-C6 alkyle, halogène, OCH3, CF3. R2 et R3, identiques ou différents représentent : Hydrogène, C1-C6 alkyle. R4 représente : a) Hydrogène ; b) C1-C6 alkyle ; c) un aryle ; d) un hétérocycle. R5 représente : Hydrogène, COR7, SO2R7, CO(CH2)nSR7, CO(CH2)nOR7, CONR7R8, CSNR7R8, CO(CH2)mCOR7. R6 représente : a) un phényle ou un naphtyle ; b) un C1-C6 alkyle, un cycloalkyle ; c) un hétérocycle ; d) NR7R8. R7 et R8, identiques ou différents, représentent : a) Hydrogène ; C1-C15 alkyle ; b) un hétérocycle ; c) un aryle. n représente : 0 à 10. m représente : 2 à 10 ; à la condition toutefois que, lorsque Z représente un groupement quinazoline ou benzimidazole, alors R5 est différent de CH2Ph ou Méthyl et n est différent de zéro.
• ST7612AA1, a Thioacetate-ω(γ-lactam carboxamide) Derivative Selected from a Novel Generation of Oral HDAC Inhibitors
  作者：Giuseppe Giannini、Loredana Vesci、Gianfranco Battistuzzi、Davide Vignola、Ferdinando M. Milazzo、Mario Berardino Guglielmi、Marcella Barbarino、Mosè Santaniello、Nicola Fantò、Marco Mor、Silvia Rivara、Daniele Pala、Maurizio Taddei、Claudio Pisano、Walter Cabri

  DOI：10.1021/jm5008209

  日期：2014.10.23

  A systematic study of medicinal chemistry aimed at identifying a new generation of HDAC inhibitors, through the introduction of a thiol zinc-binding group (ZBG) and of an amide-lactam in the ?-position of the polyethylene chain of the vorinostat scaffold, allowed the selection of a new class of potent pan-HDAC inhibitors (pan-HDACis). Simple, highly versatile, and efficient synthetic approaches were used to synthesize a library of these new derivatives, which were then submitted to a screening for HDAC inhibition as well as to a preliminary in vitro assessment of their antiproliferative activity. Molecular docking into HDAC crystal structures suggested a binding mode for these thiol derivatives consistent with the stereoselectivity observed upon insertion of amide-lactam substituents in the ?-position. ST7612AA1 (117), selected as a drug candidate for further development, showed an in vitro activity in the nanomolar range associated with a remarkable in vivo antitumor activity, highly competitive with the most potent HDAC inhibitors, currently under clinical trials. A preliminary study of PK and metabolism is also illustrated.
• Novel aminophenyl piperazine or aminophenyl piperidine derivatives inhibiting prenyl transferase proteins and method for preparing same
  申请人：——

  公开号：US20040092524A1

  公开（公告）日：2004-05-13

  The invention concerns compounds corresponding to general formula (I), wherein, in particular: W represents hydrogen, COR 6 , CSR 6 , SO 2 R 6 , CO(CH 2 ) n R 6 , (CH 2 ) n R 7 ; X represents CH or N; Y represents (CH 2 ) n , CO, CH 2 CO, CH═CHCO, CH 2 CH 2 CO; Z represents a heterocycle. When Z=pyridine, then Y is other than CO. R 1 represents hydrogen, C 1 -C 6 alkyl, halogen OCH 3 , CF 3 ; R 2 and R 3 , identical or different, represent hydrogen, C 1 -C 6 alkyl; R 4 represents a) hydrogen, b) C 1 -C 6 alkyl, c) an aryl, d) a heterocycle; R 5 represents hydrogen, COR 7 R 8 , SO 2 R 7 , CO(CH 2 ) n SR 7 , CO(CH 2 ) n OR 7 , CONR 7 R 8 , CO(CH 2 ) m COR 7 ; R 6 represents a) a phenyl or a naphthyl, b) a C 1 -C 6 alkyl, a cycloalkyl, c) a heterocycle, d) NR 7 R 8 ; R 7 and R 8 , identical or different, represent a) hydrogen, C 1 -C 15 alkyl, b) a heterocycle, c) an aryl; n represents 0 to 10; m represents 2 to 10; provided that when Z represents a quinozaline or benzimidazole group, then R 5 is other than CH 2 Ph or methyl and n is other than zero. 1

  该发明涉及与一般式（I）相对应的化合物，其中，特别是：W代表氢，COR6，CSR6，SO2R6，CO（CH2）nR6，（CH2）nR7；X代表CH或N；Y代表（CH2）n，CO，CH2CO，CH═CHCO，CH2CH2CO；Z代表杂环。当Z=吡啶时，Y不是CO。R1代表氢，C1-C6烷基，卤素OCH3，CF3；R2和R3，相同或不同，代表氢，C1-C6烷基；R4代表a）氢，b）C1-C6烷基，c）芳基，d）杂环；R5代表氢，COR7R8，SO2R7，CO（CH2）nSR7，CO（CH2）nOR7，CONR7R8，CO（CH2）mCOR7；R6代表a）苯基或萘基，b）C1-C6烷基，环烷基，c）杂环，d）NR7R8；R7和R8，相同或不同，代表a）氢，C1-C15烷基，b）杂环，c）芳基；n表示0到10；m表示2到10；前提是当Z代表喹唑啉或苯并咪唑基团时，R5不是CH2Ph或甲基，n不是零。