[(14Z,16E,18S,19S,20R,21R,22R,23S,24R,25S,26E,29S)-19,21-dihydroxy-4-(2-hydroxyethyl)-25-methoxy-2,14,18,20,22,24,29-heptamethyl-9,13,30-trioxo-28,32-dioxa-4,5,12-triazapentacyclo[27.2.1.03,7.06,11.08,31]dotriaconta-1(31),2,5,7,10,14,16,26-octaen-23-yl] acetate | 1338238-81-5

• 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: [(14Z,16E,18S,19S,20R,21R,22R,23S,24R,25S,26E,29S)-19,21-dihydroxy-4-(2-hydroxyethyl)-25-methoxy-2,14,18,20,22,24,29-heptamethyl-9,13,30-trioxo-28,32-dioxa-4,5,12-triazapentacyclo[27.2.1.03,7.06,11.08,31]dotriaconta-1(31),2,5,7,10,14,16,26-octaen-23-yl] acetate
• CAS: 1338238-81-5
• 化学式: C₃₉H₄₉N₃O₁₁
• 分子量: 735.832
• InChiKey: WBEJMUYLRASZQS-ACYXEZBUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  53.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  195.74
• 氢给体数：
  4.0
• 氢受体数：
  13.0

反应信息

• 作为产物：
  描述：

  8-(p-toluenesulfonyloxy)rifamycin S 、 (2-hydroxyethyl)hydrazine hydrochloride 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以7 mg的产率得到[(14Z,16E,18S,19S,20R,21R,22R,23S,24R,25S,26E,29S)-19,21-dihydroxy-4-(2-hydroxyethyl)-25-methoxy-2,14,18,20,22,24,29-heptamethyl-9,13,30-trioxo-28,32-dioxa-4,5,12-triazapentacyclo[27.2.1.03,7.06,11.08,31]dotriaconta-1(31),2,5,7,10,14,16,26-octaen-23-yl] acetate
  参考文献：
  名称：

  Synthesis and structure–activity relationships of novel substituted 8-amino, 8-thio, and 1,8-pyrazole congeners of antitubercular rifamycin S and rifampin

  摘要：

  A series of rifamycin S and rifampin analogues incorporating substituted 8-amino, 8-thio, and 1,8-pyrazole substituents has been synthesized. The compounds were made by activation of the C-8 phenol as a sulfonate ester, followed by displacement with selected nitrogen and sulfur nucleophiles. The analogues were screened in assays to quantify their antitubercular activity under both aerobic and anaerobic conditions, and for inhibition of wild-type Mycobacterium tuberculosis (MTB) RNAP and rifamycin-resistant MTB RNAP (S450L) via an in vitro rolling circle transcription assay. Additionally, the MIC(90) values were determined for these analogues against Escherichia coli strains. Although none of the analogues displayed superior enzymatic or microbiological activity to their parent scaffolds, the results are consistent with the Rif C-8 hydroxyl acting as a hydrogen bond acceptor with S450 and that Rif resistance in the S450L mutant is due to loss of this hydrogen bond. Representative analogues were also evaluated in the human pregnane X receptor (PXR) activation assay. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.054