2-(5-(哌啶-4-基)-1,2,4-噁二唑-3-基)吡嗪 | 849925-00-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 2-(5-(哌啶-4-基)-1,2,4-噁二唑-3-基)吡嗪
• 英文名称: 2-(5-piperidin-4-yl-1,2,4-oxadiazol-3-yl)pyrazine
• 英文别名: 5-piperidin-4-yl-3-pyrazin-2-yl-1,2,4-oxadiazole
• CAS: 849925-00-4
• 化学式: C₁₁H₁₃N₅O
• mdl: MFCD03426077
• 分子量: 231.257
• InChiKey: KYFNBVXPLAKRKM-UHFFFAOYSA-N

物化性质

• 熔点：
  87～89℃

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  4,4,4-三氟丁酸 、 2-(5-(哌啶-4-基)-1,2,4-噁二唑-3-基)吡嗪 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 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 0.08h， 以37%的产率得到4,4,4-trifluoro-1-[4-(3-pyrazin-2-yl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]butan-1-one
  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

• [EN] 2-SULFONYLAMINO-4-HETEROARYL BUTYRAMIDE ANTAGONISTS OF CCR10<br/>[FR] ANTAGONISTES DE 2-SULFONYLAMINO-4-HÉTÉROARYL BUTYRAMIDE DE CCR10
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2009126675A1

  公开（公告）日：2009-10-15

  This invention relates to a compound of formula (I) and the pharmaceutically acceptable salts thereof wherein R1, R2, R4. Ar and Het are as defined herein. The invention also relates to methods of using the compound of formula (I) to treat a diseases and disorders that are mediated or sustained through the activity of CCR10.

  本发明涉及一种具有式（I）的化合物及其药学上可接受的盐，其中R1、R2、R4、Ar和Het如本文中所定义。该发明还涉及使用式（I）的化合物治疗通过CCR10活性介导或维持的疾病和紊乱的方法。
• [EN] FUSED IMIDAZOLES FOR CANCER TREATMENT<br/>[FR] IMIDAZOLES FUSIONNÉS POUR LE TRAITEMENT DU CANCER
  申请人：BAYER SCHERING PHARMA AG

  公开号：WO2009021990A1

  公开（公告）日：2009-02-19

  Compounds of Formula (I), a tautomer or stereoisomer thereof, or a salt thereof,wherein ring B and the imidazole to which it is fused, R4, R6 and R7 have the meanings as given in the description and the claims, are effective inhibi tors of the Pi3K/Akt pathway.

  式(I)的化合物，其互变异构体或立体异构体，或其盐，其中环B和与其融合的咪唑，R4、R6和R7的含义如描述和权利要求中所述，是Pi3K/Akt途径的有效抑制剂。
• FUSED BICYCLIC IMIDAZOLES
  申请人：HOLDER Swen

  公开号：US20090156604A1

  公开（公告）日：2009-06-18

  Compounds of formula (I) a tautomer or stereoisomer thereof, or a salt thereof, wherein ring B and the imidazole to which it is fused, R4, R6 and R7 have the meanings as given in the description and the claims, are effective inhibitors of the Pi3K/Akt pathway.

  式(I)的化合物或其互变异构体或立体异构体，或其盐，其中环B和其融合的咪唑环，R4，R6和R7的含义如描述和权利要求中所述，是Pi3K/Akt途径的有效抑制剂。
• Electrochemical Aminoxyl-Mediated α-Cyanation of Secondary Piperidines for Pharmaceutical Building Block Diversification
  作者：Alastair J. J. Lennox、Shannon L. Goes、Matthew P. Webster、Hannes F. Koolman、Stevan W. Djuric、Shannon S. Stahl

  DOI：10.1021/jacs.8b08145

  日期：2018.9.12

  Secondary piperidines are ideal pharmaceutical building blocks owing to the prevalence of piperidines in commercial drugs. Here, we report an electrochemical method for cyanation of the heterocycle adjacent to nitrogen without requiring protection or substitution of the N-H bond. The reaction utilizes ABNO (9-azabicyclononane N-oxyl) as a catalytic mediator. Electrochemical oxidation of ABNO generates

  由于哌啶在商业药物中的普遍存在，二级哌啶是理想的药物成分。在这里，我们报告了一种无需保护或取代 NH 键即可使与氮相邻的杂环氰化的电化学方法。该反应使用 ABNO（9-氮杂双环壬烷 N-氧基）作为催化介质。ABNO 的电化学氧化产生相应的氧代铵物质，促进 2°哌啶脱氢为环亚胺，然后加入氰化物。低电位介导的电解过程与哌啶环上的各种杂环和氧化敏感取代基相容，并能够合成非天然氨基酸。
• 2-SULFONYLAMINO-4-HETEROARYL BUTYRAMIDE ANTAGONISTS OF CCR10
  申请人：Abeywardane Asitha

  公开号：US20110275800A1

  公开（公告）日：2011-11-10

  This invention relates to a compound of formula (I) and the pharmaceutically acceptable salts thereof wherein R 1 , R 2 , R 4 . Ar and Het are as defined herein. The invention also relates to methods of using the compound of formula (I) to treat a diseases and disorders that are mediated or sustained through the activity of CCR 10 .

  本发明涉及公式(I)的化合物及其药学上可接受的盐，其中R1、R2、R4、Ar和Het的定义如本文所述。本发明还涉及使用公式(I)的化合物治疗通过CCR10活性介导或持续的疾病和障碍的方法。