(1R,3S)-cyclohexane-1,3-diamine dihydrochloride

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (1R,3S)-cyclohexane-1,3-diamine dihydrochloride
• 英文别名: cis-cyclohexane-1,3-diamine dihydrochloride；cis-cyclohexane-1,3-diyldiamine; dihydrochloride；cis-Cyclohexan-1,3-diyldiamin; Dihydrochlorid；cis-cyclohexane-1,3-diaMine hydrochloride；(1R,3S)-cyclohexane-1,3-diamine;hydrochloride
• 化学式: C₆H₁₄N₂*2ClH
• 分子量: 187.112
• InChiKey: MVUYVVKSXCLYSP-KNCHESJLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.64
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  52
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,3S)-cyclohexane-1,3-diamine dihydrochloride 在 cesium hydroxide 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Serendipity in drug-discovery: A new series of 2-(benzyloxy)benzamides as TRPM8 antagonists

  摘要：

  A new series of 2-(benzyloxy) benzamides are presented that are potent functional antagonists of TRPM8 and possess improved LipE and LE compared to the original lead. They were discovered through a series of compound libraries and we present a powerful visualization method for the chemical space explored with each library. Remarkably this new series originated from the highest risk design strategy where compounds were synthesised with the least degree of similarity to the lead structure. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.016
• 作为产物：
  描述：

  反-1,3-环己烷二胺 在 盐酸 作用下， 以49%的产率得到(1R,3S)-cyclohexane-1,3-diamine dihydrochloride
  参考文献：
  名称：

  Serendipity in drug-discovery: A new series of 2-(benzyloxy)benzamides as TRPM8 antagonists

  摘要：

  A new series of 2-(benzyloxy) benzamides are presented that are potent functional antagonists of TRPM8 and possess improved LipE and LE compared to the original lead. They were discovered through a series of compound libraries and we present a powerful visualization method for the chemical space explored with each library. Remarkably this new series originated from the highest risk design strategy where compounds were synthesised with the least degree of similarity to the lead structure. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.016

文献信息

• Synthesis, antiproliferative activity in cancer cells and DNA interaction studies of [Pt(cis-1,3-diaminocycloalkane)Cl2] analogs
  作者：James D. Hoeschele、Jana Kasparkova、Hana Kostrhunova、Olga Novakova、Jitka Pracharova、Paul Pineau、Viktor Brabec

  DOI：10.1007/s00775-020-01809-9

  日期：2020.9

  platinum(II) complexes incorporating the Pt(1,n-diaminocycloalkane) moiety is kiteplatin ([Pt(cis-1,4-DACH)Cl2], DACH = diaminocyclohexane). We report here our progress in evaluating the role of the cycloalkyl moiety in these complexes focusing on the synthesis, characterization, evaluation of the antiproliferative activity in tumor cells and studies of the mechanism of action of new [Pt(cis-1,3-diaminocycloalkane)Cl2]

  摘要 寻找更有效的铂类抗癌药物已导致数百种新的铂类复合物的设计，合成和临床前测试。该搜索结果导致第三代Pt（II）抗癌药[Pt（1,2-二氨基环己烷）（草酸盐）]，奥沙利铂被认可并获得FDA的批准，它是治疗结肠直肠和胃肠道癌的有效药物。引入Pt（1，n-二氨基环烷烃）部分的抗癌铂（II）配合物类别的另一个有希望的例子是凯铂（[Pt（顺式-1,4 -DACH）Cl 2]，DACH ＝二氨基环己烷）。我们在这里报告我们在评估环烷基部分在这些复合物中的作用方面的进展，重点是合成，表征，评估肿瘤细胞中抗增殖活性以及研究新的[Pt（顺式-1,3-二氨基环烷烃）的作用机理。）Cl 2 ]配合物，其中顺式-1，3-二氨基环烷烃基包含环丁基，环戊基和环己基部分。我们证明[Pt（顺-1,3-DACH）Cl 2 ]破坏癌细胞比其他两个研究的1,3-二氨基环烷衍生物或顺铂更大的功效。此外，研究的[Pt（顺式-1
• Isomer formation in the binding of [PtCl2(cis-cyclohexane-1,3-diamine)] to oligonucleotides and the X-ray crystal structure of [PtCl2(cis-cyclohexane-1,3-diamine)]·dimethylformamide†
  作者：S. Tsuey Cham、Connie I. Diakos、Leanne T. Ellis、Ronald R. Fenton、Vivienne P. Munk、Barbara A. Messerle、Trevor W. Hambley

  DOI：10.1039/b104502b

  日期：——

  The crystal structure of [PtCl2(cis-1,3-chxn)] (cis-1,3-chxn = (cis-cyclohexane-1,3-diamine)) as the dimethyformamide solvate is reported. When [PtCl2(cis-1,3-chxn)] binds to d(GpG), two isomers are formed that are readily separated by HPLC. Both the HPLC and GFAAS studies of the products show that the isomers form in a 1 ∶ 1 ratio. Competition experiments involving d(GpG) and the aquated and nonaquated forms of [PtCl2(cis-1,3-chxn)] and [PtCl2(NH3)2] showed that the slower binding of the former complex was due to slower aquation and not steric bulk. 1D and 2D NMR studies of the [Ptd(GpG)(cis-1,3-chxn)] isomers showed that both the dinucleotide and the diamine were highly fluxional, even at low temperatures, and this prevented formation of strong cross peaks in the NOESY and ROESY spectra and hence identification of the isomers. [PtCl2(cis-1,3-chxn)] was reacted with a 52-mer oligonucleotide having six GpG binding sites and the products were enzymatically digested and separated by HPLC. The two [Ptd(GpG)(cis-1,3-chxn)] stereoisomers were the only significant platinated products, again forming in a 1 ∶ 1 ratio although it had been anticipated that stereoselectivity would be observed in the reaction with the 52-mer because of the potential for steric interactions with the cis-1,3-chxn ligand. Molecular modelling revealed that the observed lack of stereoselectivity was due to the ability of the cis-1,3-chxn ligand to adopt a continuum of conformations that allow it to avoid severe steric clashes with the DNA.

  报告了[PtCl2(cis-1,3-chxn)]（cis-1,3-chxn = (cis-cyclohexane-1,3-diamine)）二甲基甲酰胺溶液的晶体结构。当[PtCl2(cis-1,3-chxn)]与 d(GpG)结合时，会形成两种异构体，并很容易通过 HPLC 分离出来。对产物进行的 HPLC 和 GFAAS 研究表明，这两种异构体的形成比例为 1 ∶ 1。涉及 d(GpG)和[PtCl2(cis-1,3-chxn)]及[PtCl2(NH3)2]的含水和非含水形式的竞争实验表明，前一种复合物的结合速度较慢是由于含水速度较慢，而不是由于立体体积。对[Ptd(GpG)(cis-1,3-chxn)]异构体进行的一维和二维核磁共振研究表明，即使在低温下，二核苷酸和二胺都具有很强的通性，这阻碍了在 NOESY 和 ROESY 光谱中形成强交叉峰，从而无法识别异构体。[PtCl2(顺式-1,3-chxn)]与具有六个 GpG 结合位点的 52 聚合寡核苷酸反应，产物经酶消化后通过高效液相色谱分离。两种[Ptd(GpG)(cis-1,3-chxn)]立体异构体是唯一重要的板化产物，同样以 1 ∶ 1 的比例形成，尽管由于与顺式-1,3-chxn 配体可能发生立体相互作用，预计在与 52-mer 反应中会观察到立体选择性。分子模型显示，之所以观察到缺乏立体选择性，是因为顺式-1,3-chxn 配体能够采用连续的构象，从而避免与 DNA 发生严重的立体冲突。
• 细胞周期蛋白依赖性激酶7(CDK7)的抑制剂
  申请人：江苏先声药业有限公司

  公开号：CN114907407A

  公开（公告）日：2022-08-16

  本发明提供了CDK7抑制剂化合物，具体的涉及一种式I所示化合物或其药学上可接受的盐，及其药物组合物、制备方法和用途，该化合物对CDK7的抑制剂效果良好。