(R)-3-(4,5-bis(benzyloxy)pyridin-2-yl)-4-(2,3-dihydroxypropyl)-1H-1,2,4-triazol-5(4H)-one | 1229937-22-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (R)-3-(4,5-bis(benzyloxy)pyridin-2-yl)-4-(2,3-dihydroxypropyl)-1H-1,2,4-triazol-5(4H)-one
• 英文别名: 5-[4,5-bis(benzyloxy)pyridin-2-yl]-4-[(2R)-2,3-dihydroxypropyl]-2,4-dihydro-3H-1,2,4-triazol-3-one；3-[4,5-bis(phenylmethoxy)pyridin-2-yl]-4-[(2R)-2,3-dihydroxypropyl]-1H-1,2,4-triazol-5-one
• CAS: 1229937-22-7
• 化学式: C₂₄H₂₄N₄O₅
• 分子量: 448.478
• InChiKey: HRKNDMOOWBCNKM-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-3-(4,5-bis(benzyloxy)pyridin-2-yl)-4-(2,3-dihydroxypropyl)-1H-1,2,4-triazol-5(4H)-one 在 吡啶 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  SAR and Structural Analysis of Siderophore-Conjugated Monocarbam Inhibitors of Pseudomonas aeruginosa PBP3

  摘要：

  A main challenge in the development of new agents for the treatment of Pseudomonas aeruginosa infections is the identification of chemotypes that efficiently penetrate the cell envelope and are not susceptible to established resistance mechanisms. Siderophore-conjugated monocarbams are attractive because of their ability to hijack the bacteria's iron uptake machinery for transport into the periplasm and their inherent stability to metallo-beta-lactamases. Through development of the SAR we identified a number of modifications to the scaffold that afforded active anti-P. aeruginosa agents with good physicochemical properties. Through crystallographic efforts we gained a better understanding into how these compounds bind to the target penicillin binding protein PBP3 and factors to consider for future design.

  DOI：

  10.1021/acsmedchemlett.5b00026
• 作为产物：
  描述：

  4,5-二苄氧基吡啶甲酸苄酯 在 一水合肼 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (R)-3-(4,5-bis(benzyloxy)pyridin-2-yl)-4-(2,3-dihydroxypropyl)-1H-1,2,4-triazol-5(4H)-one
  参考文献：
  名称：

  Preparation, Gram-Negative Antibacterial Activity, and Hydrolytic Stability of Novel Siderophore-Conjugated Monocarbam Diols

  摘要：

  A novel series of monocarbam compounds exhibiting promising antibacterial activity against multidrug resistant Gram-negative microorganisms is reported, along with the synthesis of one such molecule MC-1 (1). Also reported are structure-activity relationships associated with the in vitro and in vivo efficacy of 1 and related analogues in addition to the hydrolytic stability of such compounds and possible implications thereof.

  DOI：

  10.1021/ml200012f

文献信息

• MONOCARBAMS
  申请人：Brickner Steven Joseph

  公开号：US20100160281A1

  公开（公告）日：2010-06-24

  The invention relates to compounds of formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 as defined herein. The invention also relates to pharmaceutical compositions and methods of treating bacterial infections using compounds of formula (I).

  这项发明涉及式(I)的化合物： 其中R1，R2，R3，R4，R5和R6如本文所定义。该发明还涉及使用式(I)的化合物治疗细菌感染的药物组合物和方法。
• Monocarbams
  申请人：Brickner Steven Joseph

  公开号：US20120289455A1

  公开（公告）日：2012-11-15

  The invention relates to compounds of formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 as defined herein. The invention also relates to pharmaceutical compositions and methods of treating bacterial infections using compounds of formula (I).
• US8252782B2
  申请人：——

  公开号：US8252782B2

  公开（公告）日：2012-08-28
• US8324198B1
  申请人：——

  公开号：US8324198B1

  公开（公告）日：2012-12-04
• Preparation, Gram-Negative Antibacterial Activity, and Hydrolytic Stability of Novel Siderophore-Conjugated Monocarbam Diols
  作者：Mark E. Flanagan、Steven J. Brickner、Manjinder Lall、Jeffrey Casavant、Laura Deschenes、Steven M. Finegan、David M. George、Karl Granskog、Joel R. Hardink、Michael D. Huband、Thuy Hoang、Lucinda Lamb、Andrea Marra、Mark Mitton-Fry、John P. Mueller、Lisa M. Mullins、Mark C. Noe、John P. O'Donnell、David Pattavina、Joseph B. Penzien、Brandon P. Schuff、Jianmin Sun、David A. Whipple、Jennifer Young、Thomas D. Gootz

  DOI：10.1021/ml200012f

  日期：2011.5.12

  A novel series of monocarbam compounds exhibiting promising antibacterial activity against multidrug resistant Gram-negative microorganisms is reported, along with the synthesis of one such molecule MC-1 (1). Also reported are structure-activity relationships associated with the in vitro and in vivo efficacy of 1 and related analogues in addition to the hydrolytic stability of such compounds and possible implications thereof.