3-(25-O-desacetyl-25-O-carbonyl-cyclic-21,23-(1-methylethylidene acetal)-3-morpholino-rifamycin S)-3H-imidazole | 869187-60-0

• 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: 3-(25-O-desacetyl-25-O-carbonyl-cyclic-21,23-(1-methylethylidene acetal)-3-morpholino-rifamycin S)-3H-imidazole
• 英文别名: [(7S,9E,11S,12R,13R,14R,15R,19S,20S,21E,23Z,32R)-2-hydroxy-11-methoxy-3,7,12,14,17,17,20,24,32-nonamethyl-28-morpholin-4-yl-6,25,29,31-tetraoxo-8,16,18,33-tetraoxa-26-azapentacyclo[25.3.1.14,7.115,19.05,30]tritriaconta-1(30),2,4,9,21,23,27-heptaen-13-yl] imidazole-1-carboxylate
• CAS: 869187-60-0
• 化学式: C₄₆H₅₆N₄O₁₃
• 分子量: 872.97
• InChiKey: CQPODNGXFWYPGK-UTOLPDEWSA-N

物化性质

• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  63
• 可旋转键数：
  4
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  203
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  3-(25-O-desacetyl-25-O-carbonyl-cyclic-21,23-(1-methylethylidene acetal)-3-morpholino-rifamycin S)-3H-imidazole 在 盐酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 51.5h， 生成 25-O-desacetyl-25-O-(prop-2-ynylaminocarbonyl)-3-morpholino-rifamycin S
  参考文献：
  名称：

  New C25 carbamate rifamycin derivatives are resistant to inactivation by ADP-ribosyl transferases

  摘要：

  A novel series of 3-morpholino rifamycins in which the C25 acetate group was replaced by a carbamate group were prepared and found to exhibit-significantly improved antimicrobial activity than rifampin against Mycobacterium smegmatis. Further characterization of such compounds suggests that relatively large groups attached to the rifamycin core via a C25 carbarnate linkage prevent inactivation via ribosylation of the C23 alcohol as catalyzed by the endogenous rifampin ADP-ribosyl transferase of M. smegmatis. SAR studies of the C25 carbarnate rifamycin series against M. smegmatis and other bacteria are reported. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.016
• 作为产物：
  描述：

  在 盐酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 123.0h， 生成 3-(25-O-desacetyl-25-O-carbonyl-cyclic-21,23-(1-methylethylidene acetal)-3-morpholino-rifamycin S)-3H-imidazole
  参考文献：
  名称：

  New C25 carbamate rifamycin derivatives are resistant to inactivation by ADP-ribosyl transferases

  摘要：

  A novel series of 3-morpholino rifamycins in which the C25 acetate group was replaced by a carbamate group were prepared and found to exhibit-significantly improved antimicrobial activity than rifampin against Mycobacterium smegmatis. Further characterization of such compounds suggests that relatively large groups attached to the rifamycin core via a C25 carbarnate linkage prevent inactivation via ribosylation of the C23 alcohol as catalyzed by the endogenous rifampin ADP-ribosyl transferase of M. smegmatis. SAR studies of the C25 carbarnate rifamycin series against M. smegmatis and other bacteria are reported. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.10.016

文献信息

• C-25 carbamate rifamycin derivatives with activity against drug-resistant microbes
  申请人：Combrink Keith

  公开号：US20050256096A1

  公开（公告）日：2005-11-17

  Compounds of the current invention relate to rifamycin derivatives having antimicrobial activities, including activities against drug-resistant microorganisms. More specifically, compounds of the current invention relate to C-25 carbamate derivatives of rifamycin having another functional group or pharmacophore covalently attached to this position through a carbamate linkage. The resulting compounds exert their antimicrobial activity through a dual-function mechanism and therefore exhibit reduced frequency of resistance.

  当前发明的化合物涉及具有抗微生物活性的利福霉素衍生物，包括针对耐药微生物的活性。更具体地说，当前发明的化合物涉及利福霉素的C-25氨基甲酸酯衍生物，通过氨基甲酸酯键连接到该位置的另一个功能基团或药效团。由此产生的化合物通过双重功能机制发挥其抗微生物活性，因此表现出较低的抗药性频率。
• US7250413B2
  申请人：——

  公开号：US7250413B2

  公开（公告）日：2007-07-31
• New C25 carbamate rifamycin derivatives are resistant to inactivation by ADP-ribosyl transferases
  作者：Keith D. Combrink、Daniel A. Denton、Susan Harran、Zhenkun Ma、Katrina Chapo、Dalai Yan、Eric Bonventre、Eric D. Roche、Timothy B. Doyle、Gregory T. Robertson、Anthony S. Lynch

  DOI：10.1016/j.bmcl.2006.10.016

  日期：2007.1

  A novel series of 3-morpholino rifamycins in which the C25 acetate group was replaced by a carbamate group were prepared and found to exhibit-significantly improved antimicrobial activity than rifampin against Mycobacterium smegmatis. Further characterization of such compounds suggests that relatively large groups attached to the rifamycin core via a C25 carbarnate linkage prevent inactivation via ribosylation of the C23 alcohol as catalyzed by the endogenous rifampin ADP-ribosyl transferase of M. smegmatis. SAR studies of the C25 carbarnate rifamycin series against M. smegmatis and other bacteria are reported. (c) 2006 Elsevier Ltd. All rights reserved.