glycine-4-phenylpiperazin-1-ylamide | 359821-44-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: glycine-4-phenylpiperazin-1-ylamide
• 英文别名: 2-Amino-1-(4-phenylpiperazin-1-yl)ethan-1-one；2-amino-1-(4-phenylpiperazin-1-yl)ethanone
• CAS: 359821-44-6
• 化学式: C₁₂H₁₇N₃O
• mdl: MFCD06742064
• 分子量: 219.286
• InChiKey: ZIKLEKHJFFJJOZ-UHFFFAOYSA-N

物化性质

• 沸点：
  411.9±40.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  49.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  异喹啉-5-磺酰氯 、 glycine-4-phenylpiperazin-1-ylamide 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-(2-oxo-2-(4-phenylpiperazin-1-yl)ethyl)isoquinoline-5-sulfonamide
  参考文献：
  名称：

  From Tyrosine to Glycine:  Synthesis and Biological Activity of Potent Antagonists of the Purinergic P2X₇ Receptor

  摘要：

  The characterization of the native and recombinant P2X(7) receptor continues to be hindered by the lack of specific and subtype-selective antagonists with a "druglike" profile. However, a tyrosine derivative named KN-62 exhibits selective P2X(7) receptor-blocking properties. As a molecular simplification of KN-62, the present study was designed to evaluate the functional antagonistic properties of a novel series of glycine derivatives characterized by the presence of different phenyl-substituted piperazine moieties. Antagonistic activity of these glycine derivatives was tested on HEK293 cells transfected with the human P2X(7) receptor. The most potent P2X(7) receptor antagonist identified in this study (compound 4g) contains an o-fluorine substituent on the phenylpiperazine moiety and had an IC50 of 12.1 nM. The biological responses investigated were ATP-dependent Ca2+ influx across the plasma membrane and ethidium bromide uptake.

  DOI：

  10.1021/jm070443e
• 作为产物：
  描述：

  2-氯-1-(4-苯基哌唑)乙酮 在 盐酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 glycine-4-phenylpiperazin-1-ylamide
  参考文献：
  名称：

  取代的尿嘧啶衍生物可有效抑制聚（ADP-核糖）聚合酶-1（PARP-1）。

  摘要：

  合成了一类新的PARP-1抑制剂，即取代的稠合尿嘧啶衍生物。从IC（50）= 2microM的衍生物开始，化学优化程序导致化合物的效力增加了100倍以上（IC（50）<20nM）。另外，评估了理化和药代动力学性质。可以证明带有哌嗪或苯基取代的βAla-Gly侧链的化合物表现出最佳的整体性能。

  DOI：

  10.1016/s0960-894x(02)00602-9

文献信息

• Chemical compounds
  申请人：——

  公开号：US20030225094A1

  公开（公告）日：2003-12-04

  Compounds of the general structural formula (I) and use of the compounds and salts and solvates thereof, as therapeutic agents. 1

  通用结构式（I）的化合物及其盐和溶剂合物的用途，作为治疗剂。
• Malawska, Barbara; Kulig, Katarzyna; Gajda, Justyna, Acta poloniae pharmaceutica, 2007, vol. 64, # 2, p. 127 - 137
  作者：Malawska, Barbara、Kulig, Katarzyna、Gajda, Justyna、Szczeblewski, Dominik、Musial, Anna、Wieckowski, Krzysztof、Maciag, Dorota、Stables, James P.

  DOI：——

  日期：——
• Design, Synthesis, and Structure−Activity Relationships of Macrocyclic Hydroxamic Acids That Inhibit Tumor Necrosis Factor α Release in Vitro and in Vivo
  作者：Chu-Biao Xue、Matthew E. Voss、David J. Nelson、James J.-W. Duan、Robert J. Cherney、Irina C. Jacobson、Xiaohua He、John Roderick、Lihua Chen、Ronald L. Corbett、Li Wang、Dayton T. Meyer、Kenneth Kennedy、William F. DeGrado、Karl D. Hardman、Christopher A. Teleha、Bruce D. Jaffee、Rui-Qin Liu、Robert A. Copeland、Maryanne B. Covington、David D. Christ、James M. Trzaskos、Robert C. Newton、Ronald L. Magolda、Ruth R. Wexler、Carl P. Decicco

  DOI：10.1021/jm010127e

  日期：2001.8.1

  To search for TNF-alpha (tumor necrosis factor alpha) converting enzyme (TACE) inhibitors, we designed a new class of macrocyclic hydroxamic acids by linking the PI and P2 ' residues of acyclic anti-succinate-based hydroxamic acids. A variety of residues including amide, carbamate, alkyl, sulfonamido, Boc-amino, and amino were found to be suitable P1-P2 ' linkers. With an N-methylamide at P3 ', the 13-16-membered macrocycles prepared exhibited low micromolar activities in the inhibition of TNF-alpha release from LPS-stimulated human whole blood. Further elaboration in the P3 ' -P4 ' area using the cyclophane and cyclic carbamate templates led to the identification of a number of potent analogues with IC50 values of less than or equal to 0.2 muM in whole blood assay (WBA). Although the P3 ' area can accommodate a broad array of structurally diversified functional groups including polar residues, hydrophobic residues, and amino and carboxylic acid moieties, in both the cyclophane series and the cyclic carbamate series, a glycine residue at P3 ' was identified as a critical structural component to achieve both good in vitro potency and good oral activity. With a glycine residue at P3 ', an N-methylamide at P4 ' provided the best cyclophane analogue, SL422 (WBA IC50 = 0.22 muM, LPS-mouse ED50 = 15 mg/kg, po), whereas a morpholinylamide at P4 ' afforded the most potent and most orally active cyclic carbamate analogue, SP057 (WBA IC50 = 0.067 muM, LPS-mouse ED50 = 2.3 mg/kg, po). Further profiling for SL422 and SP057 showed that these macrocyclic compounds are potent TACE inhibitors, with K-i values of 12 and 4.2 nM in the porcine TACE assay, and are broad-spectrum MMP inhibitors. Pharmacokinetic studies in beagle dogs revealed that SL422 and SP057 are orally bioavailable, with oral bioavailabilities of 11% and 23%, respectively.
• [EN] METHOD FOR MODULATING ACTIVITY OF HCV PROTEASE THROUGH USE OF A NOVEL HCV PROTEASE INHIBITOR TO REDUCE DURATION OF TREATMENT PERIOD<br/>[FR] PROCEDE DE MODULATION DE L'ACTIVITE DE LA PROTEASE DU VHC AU MOYEN D'UN NOUVEL INHIBITEUR DE LA PROTEASE DU VHC AUX FINS DE LA REDUCTION DE LA DUREE DU TRAITEMENT
  申请人：SCHERING CORP

  公开号：WO2006130626A2

  公开（公告）日：2006-12-07

  [EN] Methods are provided for using at least one novel hepatitis C ("HCV") protease inhibitor in combination with at least one antiviral and/or immunomodulatory agent, which is different from the at least one HCV protease inhibitor, for treating a wide variety of diseases or disorders associated with hepatitis C virus by modulating the activity of HCV protease (for example HCV NS3/NS4a serine protease) and reducing HCV viral load in a subject in a reduced treatment period. With the present invention, a hepatitis C viral load is reduced in a subject to a concentration of less than 6 x10^-5 HCV virions per milliliter of plasma in a time period of less than or equal to about 24 weeks. With the present invention, a hepatitis C viral production is suppressed with an effectiveness in a range of 0.7 to 0.997.
  [FR] La présente invention se rapporte à des procédés d'utilisation d'au moins un nouvel inhibiteur de la protéase du virus de l'hépatite C (VHC) en association à au moins un agent antiviral et/ou immunomodulateur, qui est différent dudit ou desdits inhibiteurs de protéase du VHC, pour le traitement d'une grande variété de maladies ou de troubles associés au virus de l'hépatite C par modulation de l'activité de la protéase du VHC (par exemple la sérine protéase NS3/NS4a du VHC) et réduction de la charge virale du VHC chez un sujet au cours d'une période de traitement réduite. La présente invention permet une réduction de la charge virale de l'hépatite C chez un sujet à une concentration inférieure à 6x10^-5 virions du VHC par millilitre de plasma pendant une période de temps inférieure ou égale à environ 24 semaines. La présente invention permet également une suppression de la production virale de l'hépatite C avec une efficacité située dans une plage comprise entre 0,7 et 0,997.
• From Tyrosine to Glycine:  Synthesis and Biological Activity of Potent Antagonists of the Purinergic P2X₇ Receptor
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Maria Dora Carrion、Carlota Lopez Cara、Delia Preti、Olga Cruz-Lopez、Mojgan Aghazadeh Tabrizi、Allan R. Moorman、Stefania Gessi、Eleonora Fogli、Valeria Sacchetto、Pier Andrea Borea

  DOI：10.1021/jm070443e

  日期：2007.7.1

  The characterization of the native and recombinant P2X(7) receptor continues to be hindered by the lack of specific and subtype-selective antagonists with a "druglike" profile. However, a tyrosine derivative named KN-62 exhibits selective P2X(7) receptor-blocking properties. As a molecular simplification of KN-62, the present study was designed to evaluate the functional antagonistic properties of a novel series of glycine derivatives characterized by the presence of different phenyl-substituted piperazine moieties. Antagonistic activity of these glycine derivatives was tested on HEK293 cells transfected with the human P2X(7) receptor. The most potent P2X(7) receptor antagonist identified in this study (compound 4g) contains an o-fluorine substituent on the phenylpiperazine moiety and had an IC50 of 12.1 nM. The biological responses investigated were ATP-dependent Ca2+ influx across the plasma membrane and ethidium bromide uptake.