Amphotericin B aminoethyl urea

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Amphotericin B aminoethyl urea
• 英文别名: 1-[(1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-(4-amino-3,5-dihydroxy-6-methyloxan-2-yl)oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaen-36-yl]-3-(2-aminoethyl)urea
• 化学式: C₄₉H₈₀N₄O₁₆
• 分子量: 981.2
• InChiKey: GVLUYOFPEFEBPX-QIWWCUDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  69
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  350
• 氢给体数：
  14
• 氢受体数：
  18

文献信息

• AMPHOTERICIN B DERIVATIVES WITH IMPROVED THERAPEUTIC INDEX
  申请人：THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS

  公开号：US20160215012A1

  公开（公告）日：2016-07-28

  Provided are certain derivatives of amphotericin B (AmB) characterized by reduced toxicity and retained anti-fungal activity. Certain of the derivatives are C16 urea derivatives of AmB. Certain of the derivatives are C3, C5, C8, C9, C11, C13, or C15 deoxy derivatives of AmB. Certain of the derivatives include C3′ or C4′ modifications of the mycosamine appendage of AmB. Also provided are methods of making AmB derivatives of the invention, pharmaceutical compositions comprising AmB derivatives of the invention, and methods of use of AmB derivatives of the invention.

  提供了一些特定的两性霉素B（AmB）衍生物，其具有降低毒性和保留抗真菌活性的特点。其中一些衍生物是AmB的C16脲衍生物。其中一些衍生物是AmB的C3、C5、C8、C9、C11、C13或C15去氧衍生物。其中一些衍生物包括对AmB的甲氨葡萄糖胺附属物的C3′或C4′修饰。还提供了制备该发明的AmB衍生物的方法，包括该发明的AmB衍生物的药物组合物，以及该发明的AmB衍生物的使用方法。
• [EN] UREA DERIVATIVES OF AMPHOTERICIN B DERIVED FROM SECONDARY AMINES<br/>[FR] DÉRIVÉS D'URÉE DE L'AMPHOTÉRICINE B DÉRIVÉE D'AMINES SECONDAIRES
  申请人：UNIV ILLINOIS

  公开号：WO2016112243A1

  公开（公告）日：2016-07-14

  Provided are certain urea derivatives of amphotericin B (AmB) having improved therapeutic index compared to AmB. The compounds of the invention are less toxic than AmB and are useful to treat fungal infections. In certain embodiments the urea derivative of AmB is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof: wherein, independently for each occurrence: R represents methyl, ethyl, propyl, or isopropyl; R' represents methyl, ethyl, propyl, or isopropyl; or R and R', taken together with the nitrogen atom to which they are attached, represent a radical of a cyclic secondary amine. Also provided are methods for making the urea derivatives of AmB.

  提供了与两性霉素B（AmB）相比具有改善的治疗指数的某些尿素衍生物。本发明的化合物比AmB毒性更小，并且可用于治疗真菌感染。在某些实施例中，AmB的尿素衍生物是由以下式（I）表示的化合物或其药用可接受的盐：其中，对于每次出现独立地：R代表甲基、乙基、丙基或异丙基；R'代表甲基、乙基、丙基或异丙基；或R和R'与它们连接的氮原子一起表示环状二级胺的基团。还提供了制备AmB的尿素衍生物的方法。
• Amphotericin B derivatives with improved therapeutic index
  申请人：The Board of Trustees of the University of Illinois

  公开号：US10323057B2

  公开（公告）日：2019-06-18

  Provided are certain derivatives of amphotericin B (AmB) characterized by reduced toxicity and retained anti-fungal activity. Certain of the derivatives are C16 urea derivatives of AmB. Certain of the derivatives are C3, C5, C8, C9, C11, C13, or C15 deoxy derivatives of AmB. Certain of the derivatives include C3′ or C4′ modifications of the mycosamine appendage of AmB. Also provided are methods of making AmB derivatives of the invention, pharmaceutical compositions comprising AmB derivatives of the invention, and methods of use of AmB derivatives of the invention.

  本文提供了两性霉素 B（AmB）的某些衍生物，其特点是毒性降低，抗真菌活性保持不变。其中某些衍生物是 AmB 的 C16 脲衍生物。某些衍生物是 AmB 的 C3、C5、C8、C9、C11、C13 或 C15 脱氧核衍生物。某些衍生物包括 AmB 的霉菌胺附属物的 C3′或 C4′修饰。此外，还提供了制造本发明AmB衍生物的方法、包含本发明AmB衍生物的药物组合物以及本发明AmB衍生物的使用方法。
• [EN] AMPHOTERICIN B DERIVATIVES WITH IMPROVED THERAPEUTIC INDEX<br/>[FR] DÉRIVÉS D'AMPHOTÉRICINE B AYANT UN INDICE THÉRAPEUTIQUE AMÉLIORÉ
  申请人：UNIV ILLINOIS

  公开号：WO2015054148A1

  公开（公告）日：2015-04-16

  Provided are certain derivatives of amphotericin B (AmB) characterized by reduced toxicity and retained anti-fungal activity. Certain of the derivatives are C16 urea derivatives of AmB. Certain of the derivatives are C3, C5, C8, C9, C11, C13, or C15 deoxy derivatives of AmB. Certain of the derivatives include C3' or C4' modifications of the mycosamine appendage of AmB. Also provided are methods of making AmB derivatives of the invention, pharmaceutical compositions comprising AmB derivatives of the invention, and methods of use of AmB derivatives of the invention.