(S)-2-methyl-1-((2-nitrophenyl)sulfonyl)piperazine

• 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: (S)-2-methyl-1-((2-nitrophenyl)sulfonyl)piperazine
• 英文别名: (2S)-2-methyl-1-(2-nitrobenzenesulfonyl)piperazine；(2S)-2-methyl-1-(2-nitrophenyl)sulfonylpiperazine
• 化学式: C₁₁H₁₅N₃O₄S
• 分子量: 285.324
• InChiKey: AYFXHGBPQSZVJV-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-2-methyl-1-((2-nitrophenyl)sulfonyl)piperazine 在 四(三苯基膦)钯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 11.5h， 生成 (2S)-4-[[6-(2-methoxyethoxymethyl)pyridin-3-yl]methyl]-2-methyl-1-(2-nitrophenyl)sulfonylpiperazine
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel, potent, orally active hypoxia-inducible factor-1 inhibitors

  摘要：

  Hypoxia-inducible factor-1 (HIF-1) is the chief transcription factor regulating hypoxia-driven gene expression. HIF-1 overexpression is associated with poor prognosis in several cancers and therefore represents an attractive target for novel antitumor agents. We explored small molecule inhibitors of the HIF-1 pathway. Using high-throughput-screening, we identified benzanilide compound 1 (IC50=560 nM) as a seed. Subsequent extensive derivatization led to the discovery of compounds 43a and 51d, with anti-HIF-1 activities in vitro (IC50=21 and 0.47 nM, respectively), and in vivo. Additionally, 43a (12.5-100mg/kg) also displayed in vivo anti-tumor efficacy, without influencing body weight.

  DOI：

  10.1016/j.bmc.2014.07.020
• 作为产物：
  描述：

  tert-butyl (S)-(2-((N-(2-bromoethyl)-2-nitrophenyl)sulfonamido)propyl)carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以97%的产率得到(S)-2-methyl-1-((2-nitrophenyl)sulfonyl)piperazine
  参考文献：
  名称：

  正交保护-2-取代手性哌嗪的实用和可扩展合成

  摘要：

  描述了一种正交保护的、对映体纯的 2-取代哌嗪的合成路线。从 α-氨基酸开始，在四步内获得手性 2-取代哌嗪。关键的转化涉及正交双保护手性 1,2-二胺和原位生成的由 2-溴乙基-二苯基锍三氟甲磺酸盐衍生的乙烯基二苯基锍盐之间的氮杂迈克尔加成。进行了使用不同保护基团的进一步验证以及多克规模的合成。该方法还应用于手性1,4-二氮杂环己烷和1,4-二氮杂环己烷的构建。此外，该方法用于手性米氮平的正式合成。

  DOI：

  10.1039/d0ob01713b

文献信息

• Piperazine derivative
  申请人：Astellas Pharma Inc.

  公开号：US10710988B2

  公开（公告）日：2020-07-14

  [Problem] To provide a compound useful as an MC4 receptor agonist. [Means for Solution] The present inventors studied MC4 receptor agonists, and have found that a piperazine derivative has an MC4 receptor agonistic action, thereby completing the present invention. The piperazine derivative of the present invention has an MC4 receptor agonistic action, and can be used as an agent for preventing or treating bladder and/or urinary tract diseases, in particular, underactive bladder, hypotonic bladder, acontractile bladder, detrusor underactivity, neurogenic bladder, urethral relaxation failure, detrusor-external urethral sphincter dyssynergia, and voiding dysfunctions in benign prostatic hyperplasia.

  [问题]提供一种可用作 MC4 受体激动剂的化合物。 [解决方法]本发明者对 MC4 受体激动剂进行了研究，发现一种哌嗪衍生物具有 MC4 受体激动作用，从而完成了本发明。本发明的哌嗪衍生物具有MC4受体激动作用，可用作预防或治疗膀胱和/或尿路疾病的药物，特别是膀胱活动不足、低张性膀胱、无收缩性膀胱、逼尿肌活动不足、神经源性膀胱、尿道松弛衰竭、逼尿肌-尿道外括约肌功能障碍以及良性前列腺增生症的排尿功能障碍。
• PIPERAZINE DERIVATIVE
  申请人：Astellas Pharma Inc.

  公开号：US20190202815A1

  公开（公告）日：2019-07-04

  [Problem] To provide a compound useful as an MC 4 receptor agonist. [Means for Solution] The present inventors studied MC 4 receptor agonists, and have found that a piperazine derivative has an MC 4 receptor agonistic action, thereby completing the present invention. The piperazine derivative of the present invention has an MC 4 receptor agonistic action, and can be used as an agent for preventing or treating bladder and/or urinary tract diseases, in particular, underactive bladder, hypotonic bladder, acontractile bladder, detrusor underactivity, neurogenic bladder, urethral relaxation failure, detrusor-external urethral sphincter dyssynergia, and voiding dysfunctions in benign prostatic hyperplasia.
• Practical and scalable synthesis of orthogonally protected-2-substituted chiral piperazines
  作者：Srinivas Chamakuri、Manuj M. Shah、David C. H. Yang、Conrad Santini、Damian W. Young

  DOI：10.1039/d0ob01713b

  日期：——

  orthogonally protected, enantiomerically pure 2-substituted piperazines is described. Starting from α-amino acids, within four steps chiral 2-substituted piperazines are obtained. The key transformation involves an aza-Michael addition between an orthogonally bis-protected chiral 1,2-diamine and the in situ generated vinyl diphenyl sulfonium salt derived from 2-bromoethyl-diphenylsulfonium triflate

  描述了一种正交保护的、对映体纯的 2-取代哌嗪的合成路线。从 α-氨基酸开始，在四步内获得手性 2-取代哌嗪。关键的转化涉及正交双保护手性 1,2-二胺和原位生成的由 2-溴乙基-二苯基锍三氟甲磺酸盐衍生的乙烯基二苯基锍盐之间的氮杂迈克尔加成。进行了使用不同保护基团的进一步验证以及多克规模的合成。该方法还应用于手性1,4-二氮杂环己烷和1,4-二氮杂环己烷的构建。此外，该方法用于手性米氮平的正式合成。
• Synthesis and structure–activity relationships of novel, potent, orally active hypoxia-inducible factor-1 inhibitors
  作者：Satoshi Nagao、Yoshinobu Yamane、Setsuo Funasaka、Keigo Tanaka、Kazuki Miyazaki、Yoshihiko Kotake、Jun-ichi Kamata、Saori Watanabe-Miyano、Osamu Toyama、Yoichi Ozawa、Yoshiharu Mizui、Kiyoshi Okamoto、Daisuke Ito

  DOI：10.1016/j.bmc.2014.07.020

  日期：2014.10

  Hypoxia-inducible factor-1 (HIF-1) is the chief transcription factor regulating hypoxia-driven gene expression. HIF-1 overexpression is associated with poor prognosis in several cancers and therefore represents an attractive target for novel antitumor agents. We explored small molecule inhibitors of the HIF-1 pathway. Using high-throughput-screening, we identified benzanilide compound 1 (IC50=560 nM) as a seed. Subsequent extensive derivatization led to the discovery of compounds 43a and 51d, with anti-HIF-1 activities in vitro (IC50=21 and 0.47 nM, respectively), and in vivo. Additionally, 43a (12.5-100mg/kg) also displayed in vivo anti-tumor efficacy, without influencing body weight.