1-cyclohexyl-1,4-diazepane | 59039-67-7

• 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-cyclohexyl-1,4-diazepane
• CAS: 59039-67-7
• 化学式: C₁₁H₂₂N₂
• 分子量: 182.309
• InChiKey: YZRJEERFPFFTLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  1
• 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

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine 、 1-cyclohexyl-1,4-diazepane 在 三氟乙酸 作用下， 以 异丙醇 为溶剂， 反应 0.25h， 以78%的产率得到2-(4-cyclohexyl-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：

  1-Benzyl-4-cyclohexyl-[1,4]diazepane 以75%的产率得到
  参考文献：
  名称：

  GURYN R.; KOTELKO A.; MAJCHRZAK M., ACTA. POL. PHARM. , 1975, 32, NO 3, 293-301

  摘要：

  DOI：

文献信息

• Compound
  申请人：Toda Ayako

  公开号：US20050261177A1

  公开（公告）日：2005-11-24

  This invention relates to new polypeptide compound represented by the following general formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in the description or a salt thereof which has antimicrobial activities (especially, antifungal activities), inhibitory activity on β-1,3-glucan synthase, to process for preparation thereof, to a pharmaceutical composition comprising the same, and to a method for prophylactic and/or therapeutic treatment of infectious diseases including Pneumocystis carinii infection (e.g. Pneumocystis carinii pneumonia) in a human being or an animal.

  本发明涉及一种由以下一般式（I）表示的新多肽化合物：其中R1、R2、R3、R4、R5和R6如描述中所定义或其盐，具有抗微生物活性（特别是抗真菌活性），抑制β-1,3-葡聚糖合酶的活性，制备其的方法，包含其的药物组合物，以及用于预防和/或治疗包括肺孢子虫感染（例如肺孢子虫肺炎）在内的人类或动物的传染病的方法。
• Pose, duplicate, then elaborate: Steps towards increased affinity for inhibitors targeting the specificity surface of the Pim-1 kinase
  作者：Lukas Heyder、Phil M.M. Hochban、Corey Taylor、Florent Chevillard、Christof Siefker、Christian Iking、Hannes Borchardt、Achim Aigner、Gerhard Klebe、Andreas Heine、Peter Kolb、Wibke E. Diederich

  DOI：10.1016/j.ejmech.2022.114914

  日期：2023.1

  hits binding to Pim-1 kinase with initially modest affinity were further optimized combining computational, synthetic and crystallographic expertise, eventually resulting in potent ligands with affinities in the nanomolar range that address rarely-targeted regions of Pim-1 kinase. Starting from a set of crystallographically validated, chemically distinct fragments that bind to Pim-1 kinase but lack typical

  在这项研究中，结合计算、合成和晶体学专业知识进一步优化了与 Pim-1 激酶结合的片段大小的命中，最初具有适度的亲和力，最终产生了具有纳摩尔级亲和力的强效配体，可解决 Pim-1 的罕见靶向区域激酶。从一组经过晶体学验证的、化学上不同的片段开始，这些片段与 Pim-1 激酶结合但缺乏典型的核苷酸模拟结构，通过详尽的计算机模拟构建了一个扩展片段库反应。在对接、最小化、聚类、对排名靠前的化合物进行目视检查以及评估合成可及性的难易程度之后，合成了原始化合物或相近的衍生物，并针对 Pim-1 进行了测试。对于显示最高程度的 Pim-1 抑制的化合物，结合模式是通过晶体学确定的。按照结构导向的方法，这些在随后的设计周期中得到进一步优化，将化合物的初始亲和力提高了几个数量级，同时仅合成了相对适度数量的衍生物。计算和实验方法的结合导致开发了一种相当有效的新型分子支架，用于抑制针对特定表面区域的 Pim-1，
• Potent CCR4 antagonists: Synthesis, evaluation, and docking study of 2,4-diaminoquinazolines
  作者：Kazuhiro Yokoyama、Noriko Ishikawa、Susumu Igarashi、Noriyuki Kawano、Naoyuki Masuda、Kazuyuki Hattori、Takahiro Miyazaki、Shin-ichi Ogino、Masaya Orita、Yuzo Matsumoto、Makoto Takeuchi、Mitsuaki Ohta

  DOI：10.1016/j.bmc.2008.07.062

  日期：2008.9

  A series of CC chemokine receptor-4 (CCR4) antagonists were examined in a previous report in an attempt to improve metabolic stability in human liver microsomes. In this study, the cycloheptylamine moiety of N-cycloheptyl-6,7-dimethoxy-2-(4-pyrrolidin-1-ylpiperidin-1-yl)quinazolin-4-amine 1 was replaced with the p-chloroaniline moiety, and the resulting compound, N-(4-chlorophenyl)-6,7-dimethoxy-2-(4-pyrrolidin-1-ylpiperidin-1-yl)quinazolin-4-amine (8c), retained its potency ([S-35]GTP gamma S-binding inhibition and CCL22-induced chemotaxis in humans/mice). Based on the structure-activity relationships (SAR), a homology model was constructed for CCR4 to explain the binding mode of 8c. Overall, there was good agreement between the docking pose of the CCR4 homology model and the human [S-35] GTP gamma S assay results. Administration of 8c in a murine model of acute dermatitis showed anti-inflammatory activity (oxazolone-induced contact hypersensitivity test). (C) 2008 Elsevier Ltd. All rights reserved.
• Discovery of CX-5461, the First Direct and Selective Inhibitor of RNA Polymerase I, for Cancer Therapeutics
  作者：Mustapha Haddach、Michael K. Schwaebe、Jerome Michaux、Johnny Nagasawa、Sean E. O'Brien、Jeffrey P. Whitten、Fabrice Pierre、Pauline Kerdoncuff、Levan Darjania、Ryan Stansfield、Denis Drygin、Kenna Anderes、Chris Proffitt、Josh Bliesath、Adam Siddiqui-Jain、May Omori、Nanni Huser、William G. Rice、David M. Ryckman

  DOI：10.1021/ml300110s

  日期：2012.7.12

  Accelerated proliferation of solid tumor and hematologic cancer cells is linked to accelerated transcription of rDNA by the RNA polymerase I (Pol I) enzyme to produce elevated levels of rRNA (rRNA). Indeed, upregulation of Pol I, frequently caused by mutational alterations among tumor suppressors and oncogenes, is required for maintenance of the cancer phenotype and forms the basis for seeking selective inhibitors of Pot I as anticancer therapeutics. 2-(4-Methyl-[1,4]diazepan-1-yl)-5-oxo-5H-7-thia-1,11b-diaza-benzo[c]fluorene-6-carboxylic acid (5-methyl-pyrazin-2-ylmethyl)-amide (CX-5461, 7c) has been identified as the first potent, selective, and orally bioavailable inhibitor of RNA Pot I transcription with in vivo activity in tumor growth efficacy models. The preclinical data support the development of CX-5461 as an anticancer drug with potential for activity in several types of cancer.
• US20140275010A1
  申请人：——

  公开号：US20140275010A1

  公开（公告）日：2014-09-18