| 905847-40-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 905847-40-7
• 化学式: C₄₂H₈₀N₄O₁₂S
• 分子量: 865.183
• InChiKey: BBYMNMVOGYVHBX-XQPDVBPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.75
• 重原子数：
  59.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  204.14
• 氢给体数：
  7.0
• 氢受体数：
  15.0

反应信息

• 作为反应物：
  描述：

  在 盐酸 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  Synthesis, Structure–Activity Relationship, and Antimalarial Activity of Ureas and Thioureas of 15-Membered Azalides

  摘要：

  Azithromycin, a first member of the azalide family of macrolides, while having substantial antimalarial activity, failed as a single agent for malaria prophylaxis. In this paper we present the first analogue campaign to identify more potent compounds from this class. Ureas and thioureas of 15-membered azalides, N ''-substituted 9a(N'-carbamoyl-beta-aminoethyl), 9a-(N'-thiocarbamoyl-beta-aminoethyl), 9a-[N'-(beta-cyanoethyl)-N'-(carbarrioyl-beta-aminoethyl)], [N'-(beta-cyanoethyl)-N'-(thiocarbamoyl-beta-aminoethyl)], 9a-{N'-[beta-(ethoxycarbonyl)ethyl]-N'-(carbamoyl-beta-aminoethyl)}, and 9a-[N'-(beta-amidoethyl)-N'-(carbamoyl-beta-aminoethyl)] of 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A, were synthesized and their biological properties evaluated. The results obtained indicate a substantial improvement of the in vitro activity against P. falciparum (up to 88 times over azithromycin), particularly for compounds containing both sugar; on the macrocyclic ring and aromatic moiety on 9a-position. The improved in vitro activity was not confirmed in the mouse model, likely due to an increase in lipophilicity of these analogues leading to a higher volume of distribution. Overall, with increased in vitro activity, promising PK properties, and modest in vivo efficacy, this series of molecules represents a good starting platform for the design of novel antimalarial azalides.

  DOI：

  10.1021/jm2001585
• 作为产物：
  描述：

  9-deoxo-9-dihydro-3'-N-oxide-9a-aza-9a-homoerythromycin A 在 三乙基硼氢化锂 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.67h， 生成
  参考文献：
  名称：

  Synthesis, Structure–Activity Relationship, and Antimalarial Activity of Ureas and Thioureas of 15-Membered Azalides

  摘要：

  Azithromycin, a first member of the azalide family of macrolides, while having substantial antimalarial activity, failed as a single agent for malaria prophylaxis. In this paper we present the first analogue campaign to identify more potent compounds from this class. Ureas and thioureas of 15-membered azalides, N ''-substituted 9a(N'-carbamoyl-beta-aminoethyl), 9a-(N'-thiocarbamoyl-beta-aminoethyl), 9a-[N'-(beta-cyanoethyl)-N'-(carbarrioyl-beta-aminoethyl)], [N'-(beta-cyanoethyl)-N'-(thiocarbamoyl-beta-aminoethyl)], 9a-{N'-[beta-(ethoxycarbonyl)ethyl]-N'-(carbamoyl-beta-aminoethyl)}, and 9a-[N'-(beta-amidoethyl)-N'-(carbamoyl-beta-aminoethyl)] of 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A, were synthesized and their biological properties evaluated. The results obtained indicate a substantial improvement of the in vitro activity against P. falciparum (up to 88 times over azithromycin), particularly for compounds containing both sugar; on the macrocyclic ring and aromatic moiety on 9a-position. The improved in vitro activity was not confirmed in the mouse model, likely due to an increase in lipophilicity of these analogues leading to a higher volume of distribution. Overall, with increased in vitro activity, promising PK properties, and modest in vivo efficacy, this series of molecules represents a good starting platform for the design of novel antimalarial azalides.

  DOI：

  10.1021/jm2001585