[(2S,3R,4S,6R)-2-[[(1S,2R,5R,6S,7S,8R,9R,11R,13R,14R)-6-[(2R,4R,5S,6S)-5-acetyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-9-carbamoyloxy-2-ethyl-1,5,7,9,11,13-hexamethyl-4,12,16-trioxo-3,17-dioxa-15-azabicyclo[12.3.0]heptadecan-8-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] acetate | 433919-40-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2S,3R,4S,6R)-2-[[(1S,2R,5R,6S,7S,8R,9R,11R,13R,14R)-6-[(2R,4R,5S,6S)-5-acetyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-9-carbamoyloxy-2-ethyl-1,5,7,9,11,13-hexamethyl-4,12,16-trioxo-3,17-dioxa-15-azabicyclo[12.3.0]heptadecan-8-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] acetate
• CAS: 433919-40-5
• 化学式: C₄₃H₇₁N₃O₁₆
• 分子量: 886.047
• InChiKey: FYXOGCWJIRQKAR-PFUAOXJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  62
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  236
• 氢给体数：
  2
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  [(2S,3R,4S,6R)-2-[[(1S,2R,5R,6S,7S,8R,9R,11R,13R,14R)-6-[(2R,4R,5S,6S)-5-acetyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-9-carbamoyloxy-2-ethyl-1,5,7,9,11,13-hexamethyl-4,12,16-trioxo-3,17-dioxa-15-azabicyclo[12.3.0]heptadecan-8-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] acetate 在 盐酸 、 甲醇 、 三乙基硅烷 、 4-二甲氨基吡啶 、 三氟乙酸 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 2.0h， 生成 [(1S,2R,5R,6S,7S,8R,9R,11R,13R,14R)-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-1,5,7,9,11,13-hexamethyl-4,12,16-trioxo-9-[[(E)-3-(4-pyrimidin-2-ylphenyl)prop-2-enyl]carbamoyloxy]-3,17-dioxa-15-azabicyclo[12.3.0]heptadecan-6-yl] N-(4-fluorophenyl)carbamate
  参考文献：
  名称：

  3-O-酰基-6-O-氨基甲酰基红霉素A衍生物的合成和抗菌活性。

  摘要：

  已经合成了一系列的3-O-酰基-6-O-氨基甲酰基红霉素A衍生物。几个官能团被确定为最佳的C3取代基，并且该系列中的最佳化合物具有针对易感红霉素和耐红霉素细菌的有效体外抗菌活性。

  DOI：

  10.1016/j.bmcl.2005.10.074
• 作为产物：
  描述：

  [(2S,3S,4R,6R)-6-[[(1S,2R,5R,6S,7S,8R,9R,11R,14R)-9-carbamoyloxy-8-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-2-ethyl-1,5,7,9,11,13-hexamethyl-4,12,16-trioxo-3,17-dioxa-15-azabicyclo[12.3.0]heptadecan-6-yl]oxy]-4-methoxy-2,4-dimethyloxan-3-yl] acetate 在 potassium tert-butylate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 [(2S,3R,4S,6R)-2-[[(1S,2R,5R,6S,7S,8R,9R,11R,13R,14R)-6-[(2R,4R,5S,6S)-5-acetyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-9-carbamoyloxy-2-ethyl-1,5,7,9,11,13-hexamethyl-4,12,16-trioxo-3,17-dioxa-15-azabicyclo[12.3.0]heptadecan-8-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] acetate
  参考文献：
  名称：

  3-O-酰基-6-O-氨基甲酰基红霉素A衍生物的合成和抗菌活性。

  摘要：

  已经合成了一系列的3-O-酰基-6-O-氨基甲酰基红霉素A衍生物。几个官能团被确定为最佳的C3取代基，并且该系列中的最佳化合物具有针对易感红霉素和耐红霉素细菌的有效体外抗菌活性。

  DOI：

  10.1016/j.bmcl.2005.10.074

文献信息

• 3-Descladinosyl-6-O-carbamoyl and 6-O-carbonoyl macrolide antibacterial agents
  申请人：——

  公开号：US20040018994A1

  公开（公告）日：2004-01-29

  3-Descladinosyl-6-O-carbamoyl and 6-O-carbonoyl macrolide antibacterial agents of the formula: 1 wherein R 1 , W, R 3 , R 4 , R 5 , R 6 , X, X′, and Z are as described herein and in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.

  3-去氧糖基-6-O-碳酰胺基和6-O-碳酸酯基大环内酯类抗菌剂，其化学公式如下： 1 其中R 1 ，W，R 3 ，R 4 ，R 5 ，R 6 ，X，X′和Z如本文及描述中所述，并且其中的取代基具有描述中指出的含义。这些化合物可用作抗菌剂。
• BRIDGED CARBAMATE MACROLIDES
  申请人：Kim Heejin

  公开号：US20080027012A1

  公开（公告）日：2008-01-31

  The present invention discloses compounds of formulae (I) and (II) or pharmaceutically acceptable salts, esters, or prodrugs thereof: which exhibit antibacterial properties. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject in need of antibiotic treatment. The invention also relates to methods of treating a bacterial infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The invention further includes process by which to make the compounds of the present invention.

  本发明公开了式(I)和(II)的化合物或其药学上可接受的盐、酯或前药：这些化合物具有抗菌性能。本发明还涉及含有上述化合物的药物组合物，用于治疗需要抗生素治疗的受试者。该发明还涉及通过给予含有本发明化合物的药物组合物来治疗受试者的细菌感染的方法。该发明还包括制备本发明化合物的方法。
• Synthesis and antibacterial activity of C-6 carbamate ketolides, a novel series of orally active ketolide antibiotics
  作者：Todd C. Henninger、Xiaodong Xu、Darren Abbanat、Ellen Z. Baum、Barbara D. Foleno、Jamese J. Hilliard、Karen Bush、Dennis J. Hlasta、Mark J. Macielag

  DOI：10.1016/j.bmcl.2004.06.045

  日期：2004.9

  antibacterial ketolides is reported, which features the use of a C-6 carbamate for tethering the arylalkyl sidechain to the macrolide core. The best members of this series display in vitro and in vivo activity comparable to telithromycin. Partial epimerization at C-2, unobserved in previously reported ketolides, was noted for this series.

  据报道，有一系列新的抗菌酮醇化物，其特征在于使用C-6氨基甲酸酯将芳烷基侧链束缚在大环内酯核心上。该系列的最佳成员在体外和体内的活性均与泰利霉素相当。对于该系列，在先前报道的酮醇化物中未观察到的C-2部分差向异构体被注意到。
• Synthesis and antibacterial activity of C2-fluoro, C6-carbamate ketolides, and their C9-oximes
  作者：Xiaodong Xu、Todd Henninger、Darren Abbanat、Karen Bush、Barbara Foleno、Jamese Hilliard、Mark Macielag

  DOI：10.1016/j.bmcl.2004.12.067

  日期：2005.2

  Novel C6-carbamate ketolides with C2-fluorination and C9-oximation have been synthesized. The best compounds in this series displayed MIC values of 0.03-0.12 mug/mL against streptococci containing erm and mef resistance determinants and 2-4 mug/mL against Haemophilus influenzae. Several compounds also showed measurable activity against erm(B)-containing enterococci with MIC values of 2-8 mug/mL. In vivo activity was adversely affected by fluorination, possibly as a result of increased serum protein binding. (C) 2005 Elsevier Ltd. All rights reserved.