N-(1,1-dimethyl)-2-oxopropyl nodulisporamide | 678989-50-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N-(1,1-dimethyl)-2-oxopropyl nodulisporamide
• CAS: 678989-50-9
• 化学式: C₄₉H₆₄N₂O₆
• 分子量: 777.057
• InChiKey: CWAGRGWDVAQMOG-LRMDTHCDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.97
• 重原子数：
  57.0
• 可旋转键数：
  7.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  117.86
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  3-Amino-3-methyl-butan-2-on 、 (+)-nodulisporic acid A 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以412 mg的产率得到N-(1,1-dimethyl)-2-oxopropyl nodulisporamide
  参考文献：
  名称：

  Discovery of the Development Candidate N-tert-Butyl Nodulisporamide: A Safe and Efficacious Once Monthly Oral Agent for the Control of Fleas and Ticks on Companion Animals

  摘要：

  Nodulisporic acid A (1) is a structurally complex fungal metabolite that exhibits systemic efficacy against fleas via modulation of an invertebrate specific glutamate-gated ion channel. In order to identify a nodulisporamide suitable for monthly oral dosing in dogs, a library of 335 nodulisporamides was examined in an artificial flea feeding system for intrinsic systemic potency as well as in a mouse/bedbug assay for systemic efficacy and safety. A cohort of 66 nodulisporamides were selected for evaluation in a dog/flea model; pharmacokinetic analysis correlated plasma levels with flea efficacy. These efforts resulted in the identification of the development candidate N-tert-butyl nodulisporamide (3) as a potent and efficacious once monthly oral agent for the control of fleas and ticks on dogs and cats which was directly compared to the topical agents fipronil and imidacloprid, with favorable results obtained. Multidose studies over 3 months confirmed the in vivo ectoparasiticidal efficacy and established that 3 lacked overt mammalian toxicity. Tissue distribution studies in mice using [C-14]-labeled 3 indicate that adipose beds serve as ligand depots, contributing to the long terminal half-lives of these compounds.

  DOI：

  10.1021/jm801334v