BDM41906 | 1352079-30-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: BDM41906
• 英文别名: 5,5,5-Trifluoro-1-{4-[3-(1,3-Thiazol-2-Yl)-1,2,4-Oxadiazol-5-Yl]piperidin-1-Yl}pentan-1-One；5,5,5-trifluoro-1-[4-[3-(1,3-thiazol-2-yl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]pentan-1-one
• CAS: 1352079-30-1
• 化学式: C₁₅H₁₇F₃N₄O₂S
• 分子量: 374.387
• InChiKey: WIFDOUQOJULUSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  100
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 生成 BDM41906
  参考文献：
  名称：

  Ethionamide Boosters. 2. Combining Bioisosteric Replacement and Structure-Based Drug Design To Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors

  摘要：

  Mycobacterial transcriptional repressor EthR controls the expression of EthA, the bacterial monooxygenase activating ethionamide, and is thus largely responsible for the low sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. We recently reported structure-activity relationships of a series of 1,2,4-oxadiazole EthR inhibitors leading to the discovery of potent ethionamide boosters. Despite high metabolic stability, pharmacokinetic evaluation revealed poor mice exposure; therefore, a second phase of optimization was required. Herein a structure-property relationship study is reported according to the replacement of the two aromatic heterocycles: 2-thienyl and 1,2,4-oxadiazolyl moieties. This work was done using a combination of structure-based drug design and in vitro/ex vivo evaluations of ethionamide boosters on the targeted protein EthR and on the human pathogen Mycobacterium tuberculosis. Thanks to this process, we identified compound 42 (BDM41906), which displays improved efficacy in addition to high exposure to mice after oral administration.

  DOI：

  10.1021/jm200825u

文献信息

• Fluoralkylcarbonyl-oxadiazoles
  申请人：Universite de Droit et de la Sante de Lille 2

  公开号：US08962658B2

  公开（公告）日：2015-02-24

  The present invention relates to compounds of Formula (I) wherein R1 is chosen among the following radicals: and n=1 or 2 and m=1 or 2 with the proviso that m=2 when R1 is The present invention also relates to the use thereof as drugs, more particularly in the treatment of mycobacterial infections and more particularly in the treatment of tuberculosis.

  本发明涉及式(I)化合物，其中R1选自以下基团：且n=1或2，m=1或2，但当R1为时，m=2。本发明还涉及其作为药物的用途，更具体地用于治疗分枝杆菌感染，特别是用于治疗结核病。
• FLUORALKYLCARBONYL-OXADIAZOLES
  申请人：Universite de Droit et de la Sante de Lille 2

  公开号：US20140309238A1

  公开（公告）日：2014-10-16

  The present invention relates to compounds of Formula (I), wherein R1 is chosen among the following radicals: (II); (III); (IV), (V), (VI) (VII) and n=1 or 2 and m=1 or 2 with the proviso that m=2 when R1 is (VIII). The present invention also relates to the use thereof as drugs, more particularly in the treatment of mycobacterial infections and more particularly in the treatment of tuberculosis.

  本发明涉及式（I）的化合物，其中R1选自以下基团：（II）、（III）、（IV）、（V）、（VI）、（VII），n=1或2，m=1或2，但当R1为（VIII）时，m=2。本发明还涉及其作为药物的用途，特别是在治疗分枝杆菌感染，尤其是在治疗结核病方面的用途。
• 一种结核分歧杆菌活性抑制剂用前体药物合成方法
  申请人：安庆济达生物科技有限公司

  公开号：CN110330492A

  公开（公告）日：2019-10-15

  本发明提出了一种结核分歧杆菌活性抑制剂用前体药物合成方法，包括以下步骤：S1、向反应器A中加入乙酸，然后依次加入氯化亚铜、联砒啶、三氟甲基三甲基硅烷、氟化钾，反应后过滤得到亮黄色固体，洗涤后抽干得到三氟甲基铜的联砒啶络合物；S2、将S1得到的三氟甲基铜的联砒啶络合物以及哌啶衍生物加入反应器B中，然后加入三乙基硅烷、过硫酸钾、丙酮、去离子水，在室温下反应后，减压旋去溶剂，粗产物洗涤、浓缩后重结晶，得到目标产物。本发明原料价格低廉易获得，反应操作简单，并且得到高附加值的三氟甲基产物，只需要重结晶就能分离干净，最终产物纯度达到98％以上，反应以水为绿色溶剂，不需要无水无氧的苛刻条件，可以进行放大生产。
• [EN] 1, 2, 4 - OXADIAZOLE DERIVATIVES AS ETHR INHIBITORS FOR USE IN THE TREATMENT TUBERCULOSIS<br/>[FR] COMPOSÉS PRÉSENTANT UNE ACTIVITÉ D'INHIBITION D'ETHR, UTILISATION DESDITS COMPOSÉS EN TANT QUE MÉDICAMENTS, COMPOSITION PHARMACEUTIQUE ET PRODUIT CONTENANT LESDITS COMPOSÉS
  申请人：UNIV LILLE II DROIT & SANTE

  公开号：WO2013060744A3

  公开（公告）日：2013-06-20
• RAPID PHENOTYPE TESTS FOR ANTITUBERCULAR DRUG SENSITIVITY AND RESISTANCE
  申请人：STC, UNM

  公开号：US20170010272A1

  公开（公告）日：2017-01-12

  In one embodiment, the invention provides methods of identifying the sensitivity and resistance to therapeutic drug regimens in a subject who suffers from, or who is suspected of suffering from, a Mycobacterium infection, the method comprising administering (1) isotopically labeled Pretomanid and/or Delaminid, or (2) isotopically labeled ethionamide and/or prothionamide, or (3) isotopically labeled pyrazinamide, or (4) isotopically-labeled isoniazid to the subject and thereafter measuring levels in a subject-derived sample of one or more isotopically-labeled markers corresponding to Mycobacterium -actiwated drug metabolites or degradation products, wherein the absence of detectable levels of Mycobacterium -activated drug metabolites or degradation products indicates either that the subject does not suffer from a Mycobacterium infection or suffers from a Mycobacterium infection which is resistant to treatment with the administered drug regimen.