benzyl 4-methyl-5-oxo-1,4-diazepane-1-carboxylate | 1359072-90-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl 4-methyl-5-oxo-1,4-diazepane-1-carboxylate
• CAS: 1359072-90-4
• 化学式: C₁₄H₁₈N₂O₃
• 分子量: 262.309
• InChiKey: ZIASXLAHWGMUJC-UHFFFAOYSA-N

物化性质

• 沸点：
  438.9±45.0 °C(Predicted)
• 密度：
  1.186±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  benzyl 4-methyl-5-oxo-1,4-diazepane-1-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 24.0h， 生成 4-甲基-1,4-二氮杂环庚烷-5-酮
  参考文献：
  名称：

  Mtb PKNA/PKNB Dual Inhibition Provides Selectivity Advantages for Inhibitor Design To Minimize Host Kinase Interactions

  摘要：

  Drug resistant tuberculosis (TB) infections are on the rise and antibiotics that inhibit Mycobacterium tuberculosis through a novel mechanism could be an important component of evolving TB therapy. Protein kinase A (PknA) and protein kinase B (PknB) are both essential serine-threonine kinases in M. tuberculosis. Given the extensive knowledge base in kinase inhibition, these enzymes present an interesting opportunity for antimycobacterial drug discovery. This study focused on targeting both PknA and PknB while improving the selectivity window over related mammalian kinases. Compounds achieved potent inhibition (K-i approximate to 5 nM) of both PknA and PknB. A binding pocket unique to mycobacterial kinases was identified. Substitutions that filled this pocket resulted in a 100-fold differential against a broad selection of mammalian kinases. Reducing lipophilicity improved antimycobacterial activity with the most potent compounds achieving minimum inhibitory concentrations ranging from 3 to 5 mu M (1-2 mu g/mL) against the H37Ra isolate of M. tuberculosis.

  DOI：

  10.1021/acsmedchemlett.7b00239
• 作为产物：
  描述：

  1-Cbz-[1,4]二氮杂庚烷-5-酮 、 碘甲烷 在 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 1.25h， 以96%的产率得到benzyl 4-methyl-5-oxo-1,4-diazepane-1-carboxylate
  参考文献：
  名称：

  Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD)

  摘要：

  Discovery of a new class of DFG-out p38α kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the αC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38α IC(50)=22 nM) and highly selective (≥ 150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.

  DOI：

  10.1016/j.bmcl.2011.09.078

文献信息

• Diaminopyrimidinecarboxamide Derivative
  申请人：Nagashima Shinya

  公开号：US20090281072A1

  公开（公告）日：2009-11-12

  A compound which may be used for the prevention or treatment of respiratory diseases in which STAT 6 is concerned, particularly asthma, chronic obstructive pulmonary disease and the like is provided. A pyrimidine derivative or a salt thereof, which has an arylamino or arylethylamino group which may be substituted with a specified substituent, at the 2-position, amino group substituted with benzyl group or the like, at the 4-position, and carbamoyl group which may be substituted, at the 5-position, is provided.

  提供了一种可用于预防或治疗呼吸系统疾病，特别是哮喘、慢性阻塞性肺疾病等与STAT 6有关的化合物。该化合物为嘧啶衍生物或其盐，其在2位具有可被取代的芳基氨基或芳基乙基氨基基团，4位具有氨基取代的苯甲基基团或类似基团，5位具有可被取代的氨基甲酰基团。
• DIAMINOPYRIMIDINECARBOXAMIDE DERIVATIVE
  申请人：Nagashima Shinya

  公开号：US20110294749A1

  公开（公告）日：2011-12-01

  A compound which may be used for the prevention or treatment of respiratory diseases in which STAT 6 is concerned, particularly asthma, chronic obstructive pulmonary disease and the like is provided. A pyrimidine derivative or a salt thereof, which has an arylamino or arylethylamino group which may be substituted with a specified substituent, at the 2-position, amino group substituted with benzyl group or the like, at the 4-position, and carbamoyl group which may be substituted, at the 5-position, is provided.

  提供了一种可用于预防或治疗涉及STAT 6的呼吸系统疾病，特别是哮喘、慢性阻塞性肺疾病等的化合物。该化合物为嘧啶衍生物或其盐，其在2位具有可以被指定取代基取代的芳基氨基或芳基乙基氨基基团，在4位具有可以被苄基或类似物取代的氨基基团，并在5位具有可以被取代的氨基甲酰基团。
• US7449456B2
  申请人：——

  公开号：US7449456B2

  公开（公告）日：2008-11-11
• US8012959B2
  申请人：——

  公开号：US8012959B2

  公开（公告）日：2011-09-06
• Discovery of a novel class of non-ATP site DFG-out state p38 inhibitors utilizing computationally assisted virtual fragment-based drug design (vFBDD)
  作者：Kristofer Moffett、Zenon Konteatis、Duyan Nguyen、Rupa Shetty、Jennifer Ludington、Ted Fujimoto、Kyoung-Jin Lee、Xiaomei Chai、Haridasan Namboodiri、Michael Karpusas、Bruce Dorsey、Frank Guarnieri、Marina Bukhtiyarova、Eric Springman、Enrique Michelotti

  DOI：10.1016/j.bmcl.2011.09.078

  日期：2011.12

  Discovery of a new class of DFG-out p38α kinase inhibitors with no hinge interaction is described. A computationally assisted, virtual fragment-based drug design (vFBDD) platform was utilized to identify novel non-aromatic fragments which make productive hydrogen bond interactions with Arg 70 on the αC-helix. Molecules incorporating these fragments were found to be potent inhibitors of p38 kinase. X-ray co-crystal structures confirmed the predicted binding modes. A lead compound was identified as a potent (p38α IC(50)=22 nM) and highly selective (≥ 150-fold against 150 kinase panel) DFG-out p38 kinase inhibitor.