1-(cyclohexylmethyl)-1,4-diazepane | 178203-64-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂卓
• 英文名称: 1-(cyclohexylmethyl)-1,4-diazepane
• CAS: 178203-64-0
• 化学式: C₁₂H₂₄N₂
• mdl: MFCD09941519
• 分子量: 196.336
• InChiKey: MBOYHABMLRNQHS-UHFFFAOYSA-N

物化性质

• 沸点：
  277.0±8.0 °C(Predicted)
• 密度：
  0.928±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(cyclohexylmethyl)-1,4-diazepane 、 2-chloro-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine 在 三氟乙酸 作用下， 以 异丙醇 为溶剂， 反应 0.25h， 以81%的产率得到2-(4-(cyclohexylmethyl)-1,4-diazepan-1-yl)-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine
  参考文献：
  名称：

  Optimization of Cellular Activity of G9a Inhibitors 7-Aminoalkoxy-quinazolines

  摘要：

  Protein lysine methyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histone H3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53. We previously reported the discovery of UNC0321 (3), the most potent G9a inhibitor to date, via structure-based design and structure-activity relationship (SAR) exploration of the quinazoline scaffold represented by BIX01294 (1). Despite its very high in vitro potency, compound 3 lacks sufficient cellular potency. The design and synthesis of several generations of new analogues aimed at improving cell membrane permeability while maintaining high in vitro potency resulted in the discovery of a number of novel G9a inhibitors such as UNC0646 (6) and UNC0631 (7) with excellent potency in a variety of cell lines and excellent separation of functional potency versus cell toxicity. The design, synthesis, and cellular SAR of these potent G9a inhibitors are described.

  DOI：

  10.1021/jm200903z
• 作为产物：
  描述：

  C₁₇H₃₂N₂O₂ 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 1-(cyclohexylmethyl)-1,4-diazepane
  参考文献：
  名称：

  6-甲磺酰基-8-硝基苯并噻嗪酮类抗结核药的研制

  摘要：

  6-三氟取代的 8-硝基苯并噻嗪酮 (BTZs) 代表了一种新型抗结核药物，它们的高抗分枝杆菌活性与抑制十烯基磷酰基-β- d-核糖 2'-氧化酶 (DprE1)相关，DprE1 是结核病必需的酶分枝杆菌细胞壁的生物合成。虽然据报道临床上先进的化合物 PBTZ169 具有非凡的全细胞活性，但其水溶性差表明潜在的低生物利用度。为改善BTZ的理化性质，设计制备了一系列6-甲磺酰基取代化合物，并评价了它们的抗结核活性和DprE1抑制能力。在这些化合物中，MsPBTZ169 和化合物2和8表现出小于 40 nM 的最小抑制浓度 (MIC)；此外，这些化合物显示出增加的水溶性和可接受的代谢稳定性。综上所述，这项研究表明，6-甲磺酰基取代的 8-硝基苯并噻嗪酮衍生物与侧链修饰相结合，可能为 BTZ 型抗结核药物提供改善的类药特性。

  DOI：

  10.1021/acsmedchemlett.1c00652

文献信息

• 2-Homopiperazine-1-yl-4H-1,3-benzothiazine-4-one derivatives and process for the preparation of 2-(homo)piperazine 1,3-benzothiazine-4-one hydrochlorides
  申请人：ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (EPFL)

  公开号：EP3072889A1

  公开（公告）日：2016-09-28

  2-homopiperazine-1-yl-4H-1,3-benzothiazine-4-one derivatives of formula (I) are provided. They are useful in the treatment of bacterial infections, in particular tuberculosis, buruli ulcer and leprosy. A process for the preparation of 2-(homo)piperazine 1,3-benzothiazine-4-one hydrochlorides is also provided.

  提供式(I)的2-同型吡啶基-4H-1,3-苯并噻嗪-4-酮衍生物。它们在治疗细菌感染，特别是结核病、布鲁利溃疡和麻风方面是有用的。还提供了制备2-(同型)吡啶基-1,3-苯并噻嗪-4-酮盐酸盐的方法。
• 2-HOMOPIPERAZINE-1-YL-4H-1,3-BENZOTHIAZINE-4-ONE DERIVATIVES AND PROCESS FOR THE PREPARATION OF 2-(HOMO)PIPERAZINE 1,3-BENZOTHIAZINE-4-ONE HYDROCHLORIDES
  申请人：Ecole Polytechnique Fédérale de Lausanne (EPFL)

  公开号：EP3919480A1

  公开（公告）日：2021-12-08

  2-homopiperazine-1-yl-4H-1,3-benzothiazine-4-one derivatives of formula (I) are provided. They are useful in the treatment of bacterial infections, in particular tuberculosis, buruli ulcer and leprosy.

  提供了式 (I) 的 2-高哌嗪-1-基-4H-1,3-苯并噻嗪-4-酮衍生物。它们可用于治疗细菌感染，尤其是肺结核、布路里溃疡和麻风病。
• 2-homopiperazine-1-yl-4H-1,3-benzothiazine-4-one derivatives and process for the preparation of 2-(homo)piperazine 1,3-benzothiazine-4-one hydrochlorides
  申请人：Ecole Polytechnique Federale De Lausanne (EPFL)

  公开号：US10160754B2

  公开（公告）日：2018-12-25

  2-homopiperazine-1-yl-4H-1,3-bensothiazine-4-one derivatives of formula (I) are provided. They are useful in the treatment of bacterial infections, in particular tuberculosis, buruli ulcer and leprosy. A process for the preparation of 2-(homo)piperazine 1,3-benzothiazine-4-one hydrochlorides is also provided.

  提供了式 (I) 的 2-高哌嗪-1-基-4H-1,3-苯并噻嗪-4-酮衍生物。它们可用于治疗细菌感染，特别是肺结核、布路里溃疡和麻风病。此外，还提供了一种制备 2-(同系)哌嗪-1,3-苯并噻嗪-4-酮盐酸盐的工艺。
• PROCESS FOR THE PREPARATION OF 2- (HOMO)PIPERAZINE 1,3-BENZOTHIAZINE-4-ONE HYDROCHLORIDES
  申请人：Ecole Polytechnique Fédérale de Lausanne (EPFL)

  公开号：EP3274339B1

  公开（公告）日：2021-10-13
• 2-HOMOPIPERAZINE-1-YL-4H-1,3-BENZOTHIAZINE-4-ONE DERIVATIVES AND PROCESS FOR THE PREPARATION OF 2- (HOMO)PIPERAZINE 1,3-BENZOTHIAZINE-4-ONE HYDROCHLORIDES
  申请人：Ecole Polytechnique Federale De Lausanne (EPFL)

  公开号：US20180051016A1

  公开（公告）日：2018-02-22

  2-homopiperazine-1-yl-4H-1, 3-bensothiazine-4-one derivatives of formula (I) are provided. They are useful in the treatment of bacterial infections, in particular tuberculosis, buruli ulcer and leprosy. A process for the preparation of 2-(homo)piperazine 1, 3-benzothiazine-4-one hydrochlorides is also provided.