(R)-(2-methylpiperazin-1-yl)(phenyl)methanone | 619331-53-2

• 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: (R)-(2-methylpiperazin-1-yl)(phenyl)methanone
• 英文别名: (R)-N-(benzoyl)-2-methylpiperazine；(R)-2-Methyl-1-benzoylpiperazine；[(2R)-2-methylpiperazin-1-yl]-phenylmethanone
• CAS: 619331-53-2
• 化学式: C₁₂H₁₆N₂O
• 分子量: 204.272
• InChiKey: SXAIXGMQDJUBDK-SNVBAGLBSA-N

物化性质

• 沸点：
  345.3±35.0 °C(Predicted)
• 密度：
  1.071±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R)-(2-methylpiperazin-1-yl)(phenyl)methanone 、 N-苄氧羰基-L-酪氨酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 benzyl ((S)-1-((R)-4-benzoyl-3-methylpiperazin-1-yl)-3-(4-hydroxyphenyl)-1-oxopropan-2-yl)carbamate
  参考文献：
  名称：

  Synthesis and structure–activity relationship studies of tyrosine-based antagonists at the human P2X7 receptor

  摘要：

  Analogues of the P2X(7) receptor antagonist KN-62, modified at the piperazine and arylsulfonyl groups, were synthesized and assayed at the human P2X(7) receptor for inhibition of BzATP-induced effects, that is, uptake of a fluorescent dye (ethidium bromide) in stably transfected HEK293 cells and IL-1 beta release in differentiated THP-1 cells. Substitution of the arylsulfonyl, moiety with a nitro group increased antagonistic potency relative to methyl substitution, such that compound 21 was slightly more potent than KN-62. Substitution with D-tyrosine in 36 and sterically bulky tyrosyl 3,5-dimethyl groups in 9 enhanced antagonistic potency. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.077

文献信息

• Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir
  作者：Tao Wang、Yasu Ueda、Zhongxing Zhang、Zhiwei Yin、John Matiskella、Bradley C. Pearce、Zheng Yang、Ming Zheng、Dawn D. Parker、Gregory A. Yamanaka、Yi-Fei Gong、Hsu-Tso Ho、Richard J. Colonno、David R. Langley、Pin-Fang Lin、Nicholas A. Meanwell、John F. Kadow

  DOI：10.1021/acs.jmedchem.8b00759

  日期：2018.7.26

  leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclinical species. However, the physical properties of 3 limited plasma exposure at higher doses, both in preclinical studies and in clinical trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug

  描述了从1开始递送替米沙韦（3，BMS-626529）的HIV-1附着抑制剂（AIs）的4-甲氧基-6-氮杂吲哚系列的优化。通过将N-连接的，sp 2-杂化的杂芳基环并入杂环核的7位，可获得最有效的药效和药代动力学（PK）性能提高。遵守共面性模型的化合物可提供靶向的抗病毒效力，从而鉴定出3种具有为三种临床前物种提供靶向暴露和PK特性的特征。但是3的物理性质在临床前研究和临床试验中，由于溶解和/或溶解度受限的吸收而限制了较高剂量的血浆暴露，这是膦酰氧甲基前药4（BMS-663068，fostemsavir）的制备所解决的缺陷。4的缓释制剂目前正处于III期临床试验中，已显示出有望在高度治疗经验丰富的HIV-1感染患者中作为药物联合疗法的一部分。
• Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
  申请人：——

  公开号：US20040110785A1

  公开（公告）日：2004-06-10

  This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.

  这项发明提供了具有药物和生物影响特性的化合物，它们的药物组合物和使用方法。具体而言，该发明涉及吡啶并咪唑酮乙酰基哌嗪衍生物。这些化合物具有独特的抗病毒活性，无论是单独使用还是与其他抗病毒药物、抗感染剂、免疫调节剂或HIV进入抑制剂结合使用。更具体地，本发明涉及治疗HIV和艾滋病。
• [EN] PIPERAZINE DERIVATIVES FOR USE IN THERAPY<br/>[FR] DÉRIVÉS DE PIPÉRAZINE DESTINÉS À ÊTRE UTILISÉS EN THÉRAPIE
  申请人：GLAXO GROUP LTD

  公开号：WO2010102663A1

  公开（公告）日：2010-09-16

  The present invention relates to novel piperazine derivatives (I) with affinity for Cav2.2 calcium channels and which are capable of interfering with Cav2.2 calcium channels; to processes for their preparation; to pharmaceutical compositions containing them; and to the use of such compounds in therapy.

  本发明涉及具有亲和力Cav2.2钙通道的新型哌嗪衍生物（I），能够干扰Cav2.2钙通道；其制备方法；含有它们的药物组合物；以及在治疗中使用这类化合物。
• Bicyclo 4.4.0 antiviral derivatives
  申请人：——

  公开号：US20040009985A1

  公开（公告）日：2004-01-15

  This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with amido piperazine derivatives. These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.

  这项发明提供了具有药物和生物影响特性的化合物，它们的药物组合物和使用方法。具体而言，该发明涉及酰胺哌嗪衍生物。这些化合物具有独特的抗病毒活性，无论是单独使用还是与其他抗病毒药物、抗感染剂、免疫调节剂或HIV进入抑制剂结合使用。更具体地说，本发明涉及治疗HIV和艾滋病。
• Antiviral azaindole derivatives
  申请人：——

  公开号：US20020119982A1

  公开（公告）日：2002-08-29

  The present invention is directed to a series of chemical entities that express HIV-1 inhibitory activities.

  本发明涉及一系列具有HIV-1抑制活性的化学实体。