2-{[5-(2-methylbenzothiazol-5-yloxymethyl)isoxazole-3-carbonyl]-(S)-amino}-4-methylsulfanylbutyric acid methyl ester | 1193343-11-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-{[5-(2-methylbenzothiazol-5-yloxymethyl)isoxazole-3-carbonyl]-(S)-amino}-4-methylsulfanylbutyric acid methyl ester
• 英文别名: methyl (2S)-2-[[5-[(2-methyl-1,3-benzothiazol-5-yl)oxymethyl]-1,2-oxazole-3-carbonyl]amino]-4-methylsulfanylbutanoate
• CAS: 1193343-11-1
• 化学式: C₁₉H₂₁N₃O₅S₂
• 分子量: 435.525
• InChiKey: DEOKEZNHRSJZGW-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  157
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (2S)-2-氨基-4-甲硫基丁酸甲酯 、 5-(2-methylbenzothiazol-5-yloxymethyl)isoxazole-3-carboxylic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以51.7%的产率得到2-{[5-(2-methylbenzothiazol-5-yloxymethyl)isoxazole-3-carbonyl]-(S)-amino}-4-methylsulfanylbutyric acid methyl ester
  参考文献：
  名称：

  Searching for New Cures for Tuberculosis: Design, Synthesis, and Biological Evaluation of 2-Methylbenzothiazoles

  摘要：

  The actual development and clinical use of new therapeutics for tuberculosis (TB) have remained stagnant for years because of the complexity of the disease process, the treatment of which at present requires the administration of drug combinations over a 6 month period. There is thus all urgent need for the discovery and development of novel, more active, and less toxic anti-TB agents. In this study, we report on the chemistry and biology of a series of potent 5-(2-methylbenzothiazol-5-yloxy-methyl)isoxazole-3-carboxamide derivatives, which proved to be active against replicating Mycobacterium tuberculosis (Mtb) H(37)Rv. The most potent compounds 7j and 7s were found to inhibit Mtb growth at micromolar concentrations, with MIC values of 1.4 and 1.9 mu M, respectively. Impressively, all active compounds were nontoxic toward Vero cells (IC50 > 128 mu M). Moreover, the best of these compounds were also tested against protozoan parasites, and some of these compounds were found to show activity, especially against Plasmodium falciparum. These studies thus suggest that certain 2-methylbenzothiazole based compounds may serve as promising lead scaffolds for further elaboration as anti-TB drugs and as possible antimalaria drugs.

  DOI：

  10.1021/jm901112f