ethyl 4-(piperazin-1-ylmethyl)-benzoate | 1177490-59-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-(piperazin-1-ylmethyl)-benzoate
• 英文别名: Ethyl 4-[(piperazin-1-yl)methyl]benzoate；ethyl 4-(piperazin-1-ylmethyl)benzoate
• CAS: 1177490-59-3
• 化学式: C₁₄H₂₀N₂O₂
• 分子量: 248.325
• InChiKey: DFNLBHGWXMPXOS-UHFFFAOYSA-N

物化性质

• 沸点：
  369.6±32.0 °C(Predicted)
• 密度：
  1.097±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(piperazin-1-ylmethyl)-benzoate 、 1-propyl-8-[4-[[[p-nitrophenyl]oxy]sulfonyl]phenyl]xanthine 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以67%的产率得到ethyl-4-((4-(4-(2,6-dioxo-1-propyl-2,3,6,7-tetrahydro-1H-purin-8-yl)phenylsulfonyl)piperazin-1-yl)methyl)benzoate
  参考文献：
  名称：

  A_2B Adenosine Receptor Antagonists with Picomolar Potency

  摘要：

  The A(2B) adenosine receptor (A(2B)AR) was proposed as a novel target for the (immuno)therapy of cancer since A(2B)AR blockade results in antiproliferative, antiangiogenic, antimetastatic, and immunostimulatory effects. In this study, we explored the structure-activity relationships of xanthin-8-yl-benzenesulfonamides mainly by introducing a variety of linkers and substituents attached to the sulfonamide residue. A new, convergent strategy was established, which facilitated the synthesis of the target compounds. Many of the new compounds exhibited subnanomolar affinity for the A(2B)AR combined with high selectivity. Functional groups were introduced, which will allow the attachment of dyes and other reporter groups. 8-(4((4-(4-Bromophenyl)piperazin-1-yl)sulfonyl)phenyl)-1-propylxanthine (34, PSB-1901) was the most potent A(2B)-antagonist (K-i 0.0835 nM, K-B 0.0598 nM, human A(2B)AR) with >10 000-fold selectivity versus all other AR subtypes. It was similarly potent and selective at the mouse A(2B)AR, making it a promising tool for preclinical studies. Computational studies predicted halogen bonding to contribute to the outstanding potency of 34.

  DOI：

  10.1021/acs.jmedchem.9b00071
• 作为产物：
  描述：

  哌嗪 、 4-氯甲基苯甲酸乙酯 以 四氢呋喃 为溶剂， 反应 4.0h， 以57%的产率得到ethyl 4-(piperazin-1-ylmethyl)-benzoate
  参考文献：
  名称：

  Rational modifications, synthesis and biological evaluation of new potential antivirals for RSV designed to target the M2-1 protein

  摘要：

  Respiratory syncytial virus (RSV) is the main cause of lower respiratory tract diseases in infants and young children, with potentially serious and fatal consequences associated with severe infections. Despite extensive research efforts invested in the identification of therapeutic measures, no vaccine is currently available, while treatment options are limited to ribavirin and palivizumab, which both present significant limitations. While clinical and pre-clinical candidates mainly target the viral fusion protein, the nucleocapsid protein or the viral polymerase, our focus has been the identification of new antiviral compounds targeting the viral M2-1 protein, thanks to the presence of a zinc-ejecting group in their chemical structure. Starting from an anti-RSV hit we had previously identified with an in silico structure-based approach, we have designed, synthesised and evaluated a new series of dithiocarbamate analogues, with which we have explored the antiviral activity of this scaffold. The findings presented in this work may provide the basis for the identification of a new antiviral lead to treat RSV infections.

  DOI：

  10.1016/j.bmc.2020.115401

文献信息

• Novel 1,3-disubstituted pyrrolo[1,2-a]azepinone derivatives having
  申请人：Rhone-Poulenc Sante

  公开号：US04769366A1

  公开（公告）日：1988-09-06

  Pyrrolo[1,2-a]azepinone derivatives of formula: ##STR1## in which R.sub.3 is H or halogen and either (A) R is benzyl or phenylthio in which the phenyls are optionally substituted by one or more halogens or hydroxy, alkyl, alkyloxy or alkylthio radicals, R.sub.1 and R.sub.2, which may be identical or different, denote alkyl optionally substituted by dialkylamino in which the alkyls are optionally joined to form a 1-pyrrolidinyl, piperidino, morpholino or 1-piperazinyl ring substituted by alkyl, or alternatively R.sub.1 and R.sub.2 form a heterocyclic ring chosen from pyrrolidine, piperidine, morpholine and piperazine, substituted by alkyl, alkenyl (2 to 4 C), benzyl or phenethyl optionally substituted by halogen, alkyl, alkyloxy, alkylthio, CF.sub.3, COOH, carboxyalkyl, alkyloxycarbonyl, alkyloxycarbonylalkyl, hydroxyalkyl, or alkylcarbonyloxyalkyl in which the alkylcarbonyl has 2 to 18 C, or (B) R is phenyl optionally substituted with one or more halogens or hydroxy, alkyl, alkyloxy or alkylthio radicals and R.sub.1 and R.sub.2 together form a piperazine or homopiperazine ring substituted by hydroxyalkyl (2 to 4 C), alkenyl (2 to 4 C), alkynyl (2 to 4 C), benzyl or phenethyl optionally substituted by halogen, alkyl, alkyloxy, alkylthio, CN, CF.sub.3, COOH, carboxyalkyl, alkyloxycarbonyl, alkyloxycarbonylalkyl, hydroxyalkyl, or alkylcarbonyloxyalkyl in which the alkylcarbonyl has 2 to 18 C, the said alkyls containing, except where otherwise stated, 1 to 4 C in a straight or branched chain, and the pharmaceutically acceptable salts thereof, are useful as antipsychotics.

  公式为：##STR1##其中R.sub.3为H或卤素，且(A) R为苄基或苯基硫醚，其中苯基可选择性地被一个或多个卤素或羟基，烷基，烷氧基或烷硫基基团取代，R.sub.1和R.sub.2（可以相同也可以不同）表示可选择性地被二烷基胺基取代的烷基，其中烷基可选择性地连接以形成1-吡咯啉基，哌啶基，吗啉基或1-哌嗪基环，该环可被烷基，烯基（2至4C），苄基或苯乙基取代，该取代基可选择性地被卤素，烷基，烷氧基，烷硫基，CF.sub.3，COOH，羧基烷基，烷氧羰基，烷氧羰基烷基，羟基烷基或烷基羧酸氧烷基取代，其中烷基羧酸基含有2至18C，或(B) R为苯基，可选择性地被一个或多个卤素或羟基，烷基，烷氧基或烷硫基基团取代，而R.sub.1和R.sub.2一起形成一个哌嗪或同源哌嗪环，该环被羟基烷基（2至4C），烯基（2至4C），炔基（2至4C），苄基或苯乙基取代，该取代基可选择性地被卤素，烷基，烷氧基，烷硫基，CN，CF.sub.3，COOH，羧基烷基，烷氧羰基，烷氧羰基烷基，羟基烷基或烷基羧酸氧烷基取代，其中烷基羧酸基含有2至18C，所述烷基除非另有说明，否则在直链或支链上含有1至4C，其药物可接受的盐作为抗精神病药物有用。
• US4769366A
  申请人：——

  公开号：US4769366A

  公开（公告）日：1988-09-06
• US4826974A
  申请人：——

  公开号：US4826974A

  公开（公告）日：1989-05-02
• A_2B Adenosine Receptor Antagonists with Picomolar Potency
  作者：Jie Jiang、Catharina Julia Seel、Ahmed Temirak、Vigneshwaran Namasivayam、Antonella Arridu、Jakub Schabikowski、Younis Baqi、Sonja Hinz、Jörg Hockemeyer、Christa E. Müller

  DOI：10.1021/acs.jmedchem.9b00071

  日期：2019.4.25

  The A(2B) adenosine receptor (A(2B)AR) was proposed as a novel target for the (immuno)therapy of cancer since A(2B)AR blockade results in antiproliferative, antiangiogenic, antimetastatic, and immunostimulatory effects. In this study, we explored the structure-activity relationships of xanthin-8-yl-benzenesulfonamides mainly by introducing a variety of linkers and substituents attached to the sulfonamide residue. A new, convergent strategy was established, which facilitated the synthesis of the target compounds. Many of the new compounds exhibited subnanomolar affinity for the A(2B)AR combined with high selectivity. Functional groups were introduced, which will allow the attachment of dyes and other reporter groups. 8-(4((4-(4-Bromophenyl)piperazin-1-yl)sulfonyl)phenyl)-1-propylxanthine (34, PSB-1901) was the most potent A(2B)-antagonist (K-i 0.0835 nM, K-B 0.0598 nM, human A(2B)AR) with >10 000-fold selectivity versus all other AR subtypes. It was similarly potent and selective at the mouse A(2B)AR, making it a promising tool for preclinical studies. Computational studies predicted halogen bonding to contribute to the outstanding potency of 34.
• Rational modifications, synthesis and biological evaluation of new potential antivirals for RSV designed to target the M2-1 protein
  作者：Salvatore Ferla、Roberto Manganaro、Sara Benato、Jasmine Paulissen、Johan Neyts、Dirk Jochmans、Andrea Brancale、Marcella Bassetto

  DOI：10.1016/j.bmc.2020.115401

  日期：2020.4

  Respiratory syncytial virus (RSV) is the main cause of lower respiratory tract diseases in infants and young children, with potentially serious and fatal consequences associated with severe infections. Despite extensive research efforts invested in the identification of therapeutic measures, no vaccine is currently available, while treatment options are limited to ribavirin and palivizumab, which both present significant limitations. While clinical and pre-clinical candidates mainly target the viral fusion protein, the nucleocapsid protein or the viral polymerase, our focus has been the identification of new antiviral compounds targeting the viral M2-1 protein, thanks to the presence of a zinc-ejecting group in their chemical structure. Starting from an anti-RSV hit we had previously identified with an in silico structure-based approach, we have designed, synthesised and evaluated a new series of dithiocarbamate analogues, with which we have explored the antiviral activity of this scaffold. The findings presented in this work may provide the basis for the identification of a new antiviral lead to treat RSV infections.