1-amino-4-propargylpiperazine | 56964-23-9

• 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: 1-amino-4-propargylpiperazine
• 英文别名: 4-(Prop-2-yn-1-yl)piperazin-1-amine；4-prop-2-ynylpiperazin-1-amine
• CAS: 56964-23-9
• 化学式: C₇H₁₃N₃
• 分子量: 139.2
• InChiKey: HXSMWRURGWSXRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3甲酰利福平霉素 、 1-amino-4-propargylpiperazine 以 四氢呋喃 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  TIACUMICIN DERIVATIVES AND THEIR USE AS ANTIBIOTICS

  摘要：

  该发明涉及一种符合以下式（1）的化合物，其中R1至R4和X彼此独立地是小的功能基团，R5是-OH，或者-O-Ln-Rap-Rbq-Lt-Rar-Rbs-Re，-O-Ln-Rbq-Rd-Lt-Rbs-Re，其中L是烷基连接物，Ra是酰基，羧基或羧酰胺，Rb是环状基团，Rd是聚醚连接物，Re是小的功能末端基团，荧光染料或抗生素，但该化合物不是fidaxomicin。此外，该发明涉及该化合物在治疗疾病中的应用，以及在治疗由耐药细菌引起的感染和/或细菌感染中的应用。

  公开号：

  EP3508492A1
• 作为产物：
  描述：

  1-亚硝基-4-(2-丙炔-1-基)哌嗪 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 3.0h， 以25%的产率得到1-amino-4-propargylpiperazine
  参考文献：
  名称：

  抗生素非达霉素的半合成类似物——设计、合成和生物学评价

  摘要：

  糖化大环抗生素非达霉素（ 1 、台勾霉素 B、利拉霉素 A3）对革兰氏阳性菌表现出良好至极好的活性，并被批准用于治疗艰难梭菌感染 (CDI)。该化合物的主要限制之一是其低水溶性影响进一步的临床应用。我们报告了基于结构设计并利用天然产物的操作简单的一步无保护基制备方法合成新的非达霉素衍生物。观察到溶解度增加高达 25 倍，同时大部分活性保留。此外，制备的混合抗生素显示出改善的抗生素活性。

  DOI：

  10.1021/acsmedchemlett.0c00381

文献信息

• Cricchio; Arioli; Lancini, Farmaco, Edizione Scientifica, 1975, vol. 30, # 8, p. 605 - 619
  作者：Cricchio、Arioli、Lancini

  DOI：——

  日期：——
• Heterodimeric Rifampicin–Tobramycin conjugates break intrinsic resistance of Pseudomonas aeruginosa to doxycycline and chloramphenicol in vitro and in a Galleria mellonella in vivo model
  作者：Temilolu Idowu、Gilbert Arthur、George G. Zhanel、Frank Schweizer

  DOI：10.1016/j.ejmech.2019.04.034

  日期：2019.7

  Intrinsic resistance in Pseudomonas aeruginosa, defined by chromosomally encoded low outer membrane permeability and constitutively over-expressed efflux pumps, is a major reason why the pathogen is refractory to many antibiotics. Herein, we report that heterodimeric rifampicin-tobramycin conjugates break this intrinsic resistance and sensitize multidrug and extensively drug-resistant P. aeruginosa to doxycycline and chloramphenicol in vitro and in vivo. Tetracyclines and chloramphenicol are model compounds for bacteriostatic effects, but when combined with rifampicin-tobramycin adjuvants, their effects became bactericidal at sub MIC levels. Potentiation of tetracyclines correlates with the SAR of this class of drugs and is consistent with outer membrane permeabilization and efflux pump inhibition. Overall, this strategy finds new uses for old drugs and presents an avenue to expand the therapeutic utility of legacy antibiotics to recalcitrant pathogens such as P. aeruginosa. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Synthesis of Tridecaptin–Antibiotic Conjugates with in Vivo Activity against Gram-Negative Bacteria
  作者：Stephen A. Cochrane、Xuefeng Li、Sisi He、Min Yu、Min Wu、John C. Vederas

  DOI：10.1021/acs.jmedchem.5b01578

  日期：2015.12.24

  A series of tridecaptin-antibiotic conjugates were synthesized and evaluated for in vitro and in vivo activity against Gram-negative bacteria. Covalently linking unacylated tridecaptin A(1) (H-TriA(1)) to rifampicin, vancomycin, and erythromycin enhanced their activity in vitro but not by the same magnitude as coadministration of the peptide and these antibiotics. The antimicrobial activities of the conjugates were retained in vivo, with the H-TriA(1)-erythromycin conjugate proving a more effective treatment of Klebseilla pneumoniae infections in mice than erythromycin alone or in combination with H-TriA(1).
• [EN] TIACUMICIN DERIVATIVES AND THEIR USE AS ANTIBIOTICS<br/>[FR] DÉRIVÉS DE TIACUMICINE ET LEUR UTILISATION EN TANT QU'ANTIBIOTIQUES
  申请人：UNIV ZUERICH

  公开号：WO2019135010A1

  公开（公告）日：2019-07-11

  The invention relates to a compound according to formula (1), wherein R1 to R4 and X are independently from each other a small functional group and R5 is -OH, or a moiety consisting of specific combinations of -L-, -Ra-, -Rb-, -Rd- and Re with L being an alkyl linker, Ra being carbonyl, carboxyl or carboxamide, Rb being a cyclic moiety, Rd being a polyether linker and Re being a small functional end group, fluorescent dye or antibiotic with the proviso that the compound is not fidaxomicin. Furthermore, the invention relates to the use of the compound in the treatment of disease and the use in treating infections and/or bacterial infections caused by drug resistant bacteria.
• TIACUMICIN DERIVATIVES AND THEIR USE AS ANTIBIOTICS
  申请人：Universität Zürich

  公开号：EP3508492A1

  公开（公告）日：2019-07-10

  The invention relates to a compound according to formula (1) wherein R1 to R4 and X are independently from each other a small functional group and R5 is -OH, or -O-Ln-Rap-Rbq-Lt-Rar-Rbs-Re, -O-Ln-Rbq-Rd-Lt-Rbs-Re with L being an alkyl linker, Ra being carbonyl, carboxyl or carboxamide, Rb being a cyclic moiety, Rd being a polyether linker and Re being a small functional end group, fluorescent dye or antibiotic with the proviso that the compound is not fidaxomicin. Furthermore, the invention relates to the use of the compound in the treatment of disease and the use in treating infections and/or bacterial infections caused by drug resistant bacteria.

  该发明涉及一种符合以下式（1）的化合物，其中R1至R4和X彼此独立地是小的功能基团，R5是-OH，或者-O-Ln-Rap-Rbq-Lt-Rar-Rbs-Re，-O-Ln-Rbq-Rd-Lt-Rbs-Re，其中L是烷基连接物，Ra是酰基，羧基或羧酰胺，Rb是环状基团，Rd是聚醚连接物，Re是小的功能末端基团，荧光染料或抗生素，但该化合物不是fidaxomicin。此外，该发明涉及该化合物在治疗疾病中的应用，以及在治疗由耐药细菌引起的感染和/或细菌感染中的应用。