2-[(6S,7R,8R,12S,19S,26S)-26-(2-amino-2-oxoethyl)-8-hydroxy-19-[(R)-hydroxy(phenyl)methyl]-12-[(4-hydroxyphenyl)methyl]-7,23-dimethyl-11,14,21,28-tetraoxo-4,17,24,31,41-pentathia-10,13,20,27,37,42,43,44,45,46-decazaoctacyclo[37.2.1.12,5.115,18.122,25.129,32.06,10.033,38]hexatetraconta-1(42),2,5(46),15,18(45),22,25(44),29,32(43),33(38),34,36,39-tridecaen-36-yl]-1,3-thiazole-4-carboxylic acid | 1092397-37-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 2-[(6S,7R,8R,12S,19S,26S)-26-(2-amino-2-oxoethyl)-8-hydroxy-19-[(R)-hydroxy(phenyl)methyl]-12-[(4-hydroxyphenyl)methyl]-7,23-dimethyl-11,14,21,28-tetraoxo-4,17,24,31,41-pentathia-10,13,20,27,37,42,43,44,45,46-decazaoctacyclo[37.2.1.12,5.115,18.122,25.129,32.06,10.033,38]hexatetraconta-1(42),2,5(46),15,18(45),22,25(44),29,32(43),33(38),34,36,39-tridecaen-36-yl]-1,3-thiazole-4-carboxylic acid
• CAS: 1092397-37-9
• 化学式: C₅₃H₄₄N₁₂O₁₀S₆
• 分子量: 1201.4
• InChiKey: JZHFCZZBFHASDW-VAGMZVTLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  81
• 可旋转键数：
  8
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  508
• 氢给体数：
  8
• 氢受体数：
  23

反应信息

• 作为反应物：
  描述：

  2-[(6S,7R,8R,12S,19S,26S)-26-(2-amino-2-oxoethyl)-8-hydroxy-19-[(R)-hydroxy(phenyl)methyl]-12-[(4-hydroxyphenyl)methyl]-7,23-dimethyl-11,14,21,28-tetraoxo-4,17,24,31,41-pentathia-10,13,20,27,37,42,43,44,45,46-decazaoctacyclo[37.2.1.12,5.115,18.122,25.129,32.06,10.033,38]hexatetraconta-1(42),2,5(46),15,18(45),22,25(44),29,32(43),33(38),34,36,39-tridecaen-36-yl]-1,3-thiazole-4-carboxylic acid 、 methyl trans-4-aminocyclohexanecarboxylate hydrochloride 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 12.0h， 以32%的产率得到
  参考文献：
  名称：

  Antibacterial and Solubility Optimization of Thiomuracin A

  摘要：

  Synthetic studies of the antimicrobial secondary metabolite thiomuracin A (1) provided access to analogues in the Northern region (C2-C10). Selective hydrolysis of the C10 amide of lead compound 2 and subsequent derivatization led to novel carbon -and nitrogen-linked analogues (e.g., 3) which improved antibacterial potency across a panel of Gram-positive organisms. In addition, congeners with improved physicochemical properties were identified which proved efficacious in murine sepsis and hamster C. difficile models of disease. Optimal efficacy in the hamster model of C. difficile was achieved with compounds that possessed both potent antibacterial activity and high aqueous solubility.

  DOI：

  10.1021/acs.jmedchem.6b00726
• 作为产物：
  描述：

  [(6S,7R,8R,12S,19S,26S)-19-[(R)-acetyloxy(phenyl)methyl]-12-[(4-acetyloxyphenyl)methyl]-36-[4-[acetyl(prop-2-enyl)carbamoyl]-1,3-thiazol-2-yl]-26-(2-amino-2-oxoethyl)-7,23-dimethyl-11,14,21,28-tetraoxo-4,17,24,31,41-pentathia-10,13,20,27,37,42,43,44,45,46-decazaoctacyclo[37.2.1.12,5.115,18.122,25.129,32.06,10.033,38]hexatetraconta-1(42),2,5(46),15,18(45),22,25(44),29,32(43),33(38),34,36,39-tridecaen-8-yl] acetate 在 水 、 sodium hydroxide 作用下， 生成 2-[(6S,7R,8R,12S,19S,26S)-26-(2-amino-2-oxoethyl)-8-hydroxy-19-[(R)-hydroxy(phenyl)methyl]-12-[(4-hydroxyphenyl)methyl]-7,23-dimethyl-11,14,21,28-tetraoxo-4,17,24,31,41-pentathia-10,13,20,27,37,42,43,44,45,46-decazaoctacyclo[37.2.1.12,5.115,18.122,25.129,32.06,10.033,38]hexatetraconta-1(42),2,5(46),15,18(45),22,25(44),29,32(43),33(38),34,36,39-tridecaen-36-yl]-1,3-thiazole-4-carboxylic acid
  参考文献：
  名称：

  Antibacterial and Solubility Optimization of Thiomuracin A

  摘要：

  Synthetic studies of the antimicrobial secondary metabolite thiomuracin A (1) provided access to analogues in the Northern region (C2-C10). Selective hydrolysis of the C10 amide of lead compound 2 and subsequent derivatization led to novel carbon -and nitrogen-linked analogues (e.g., 3) which improved antibacterial potency across a panel of Gram-positive organisms. In addition, congeners with improved physicochemical properties were identified which proved efficacious in murine sepsis and hamster C. difficile models of disease. Optimal efficacy in the hamster model of C. difficile was achieved with compounds that possessed both potent antibacterial activity and high aqueous solubility.

  DOI：

  10.1021/acs.jmedchem.6b00726

文献信息

• MACROCYCLES AND THEIR USES
  申请人：Fujimoto Roger Aki

  公开号：US20090186830A1

  公开（公告）日：2009-07-23

  The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases.

  本申请描述了对治疗、预防和/或改善疾病有用的有机化合物。
• Macrocycles and Their Uses
  申请人：Novartis AG

  公开号：US20130252883A1

  公开（公告）日：2013-09-26

  The present application describes a method of treating a bacterial infection comprising administering to a subject in need thereof a pharmaceutically acceptable amount of a defined macrocycle compound.

  本申请描述了一种治疗细菌感染的方法，包括向需要治疗的对象施用一定量的定义的大环化合物的药学可接受量。
• US8476224B2
  申请人：——

  公开号：US8476224B2

  公开（公告）日：2013-07-02
• Antibacterial and Solubility Optimization of Thiomuracin A
  作者：Matthew J. LaMarche、Jennifer A. Leeds、Jason Brewer、Karl Dean、Jian Ding、Joanne Dzink-Fox、Gabe Gamber、Akash Jain、Ryan Kerrigan、Philipp Krastel、Kwangho Lee、Franco Lombardo、David McKenney、Georg Neckermann、Colin Osborne、Deborah Palestrant、Michael A. Patane、Elin M. Rann、Zachary Robinson、Esther Schmitt、Travis Stams、Stacey Tiamfook、Donghui Yu、Lewis Whitehead

  DOI：10.1021/acs.jmedchem.6b00726

  日期：2016.7.28

  Synthetic studies of the antimicrobial secondary metabolite thiomuracin A (1) provided access to analogues in the Northern region (C2-C10). Selective hydrolysis of the C10 amide of lead compound 2 and subsequent derivatization led to novel carbon -and nitrogen-linked analogues (e.g., 3) which improved antibacterial potency across a panel of Gram-positive organisms. In addition, congeners with improved physicochemical properties were identified which proved efficacious in murine sepsis and hamster C. difficile models of disease. Optimal efficacy in the hamster model of C. difficile was achieved with compounds that possessed both potent antibacterial activity and high aqueous solubility.