DDE-OH | 94142-97-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 乙烯基酸
• 英文名称: DDE-OH
• 英文别名: 2-(1-hydroxyethylidene)-5,5-dimethylcyclohexane-1,3-dione；2-(1-hydroxy-ethylidene)-5,5-dimethyl-cyclohexane-1,3-dione；2-(1-hydroxyethylidene)-5,5-dimethyl-1,3-cyclohexanedione；N-(4,4-dimethyl-2,6-dioxycyclohexylidene)ethyl alcohol；1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethanol；2-acetyldimedone
• CAS: 94142-97-9
• 化学式: C₁₀H₁₄O₃
• mdl: MFCD03001669
• 分子量: 182.219
• InChiKey: INFBGIBBJNAITK-UHFFFAOYSA-N

物化性质

• 熔点：
  35-36 °C
• 沸点：
  290.0±40.0 °C(Predicted)
• 密度：
  1.133±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.34
• 重原子数：
  13.0
• 可旋转键数：
  0.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  54.37
• 氢给体数：
  1.0
• 氢受体数：
  3.0

安全信息

• 海关编码：
  2914400090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  | 室温 干燥 |

反应信息

• 作为反应物：
  描述：

  DDE-OH 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 30.0h， 生成 N-phenylacetyl-4-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethylamino]methylpiperidine
  参考文献：
  名称：

  Design and Synthesis of Novel Biologically Active Thrombin Receptor Non-Peptide Mimetics Based on the Pharmacophoric Cluster Phe/Arg/NH₂ of the Ser₄₂-Phe-Leu-Leu-Arg₄₆ Motif Sequence:  Platelet Aggregation and Relaxant Activities

  摘要：

  The identification of the thrombin receptor has promoted the interest for the development of new therapeutic agents capable of selectively inhibiting unwanted biological effects of thrombin on various cell types. In this study we have designed and synthesized two series of new thrombin receptor antagonists based on the thrombin receptor motif sequence S42FLLR46, one possessing two (Phe/Arg) pharmacophoric groups and the other possessing three (Phe/Arg/NH2). N-(6-Guanidohexanoyl)-N'-(phenylacetyl)piperazine (1), N-(phenylacetyl)-4-(6-guanidohexanoylamidomethyl)piperidine (2), and N-(phenylacetyl)-3-(6-guanidohexanoylamido)pyrrolidine (3) (group A) carry the two pharmacophoric side chains of Phe and Arg residues incorporated on three different templates (piperazine, 4-aminomethylpiperidine, and 3-aminopyrrolidine). Compounds with three pharmacophoric groups (group B) were built similarly to group A using the same templates with the addition of an extra methylamino group leading to (S)-N-(6-guanidohexanoyl)-N'-(2-amino-3-phenylpropionyl)piperazine (4), (S)-N-(2-amino-3-phenylpropionyl)-4-(6-guanidohexanoylamidomethyl)piperidine (5), and (S)-N-(2-amino-3-phenylpropionyl)-3-(6-guanidohexanoylamido)pyrrolidine (6). Compounds were able to inhibit thrombin-induced human platelet activation even at low concentrations. In particular, among compounds in group A, compound 3 was found to be the most powerful thrombin receptor activation inhibitor, showing an IC50 of approximately 0.11 mM on platelet aggregation assay. Among compounds in group B, compound 4 was the most powerful to inhibit thrombin-induced platelet aggregation, showing an IC50 of approximately 0.09 mM. All compounds were also found to act as agonists in the rat aorta relaxation assay. Interestingly, the order or potency of these compounds as agonists of the endothelial thrombin receptor was the inverse of the order of potency of the same compounds as antagonists of the platelet thrombin receptor. Such compounds that are causing vasodilation while simultaneously inhibiting platelet aggregation would be very useful in preventing the installation of atherosclerotic lesions and deserve further investigation as potential drugs for treating cardiovascular diseases. The above findings coupled with computational analysis molecular dynamics experiments support also our hypothesis that a cluster of phenyl, guanidino, and amino groups is responsible for thrombin receptor triggering and activation.

  DOI：

  10.1021/jm031080v
• 作为产物：
  描述：

  乙酸酐 、 5,5-二甲基-1,3-环己二酮 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以89%的产率得到DDE-OH
  参考文献：
  名称：

  新型抗利什曼药剂的合成及活性

  摘要：

  我们已确定四氢吲唑如1对利什曼病的病原体Leishmania donovani显示出有效的活性。虽然之前已经探索了1的 Hsp90 活性和抗癌特性，但我们在这里展示了我们通过合成新的类似物来优化它们对L. donovani的活性，这些类似物旨在探测原生动物 Hsp90 直系同源物的疏水口袋，特别是通过嵌入支架中的胺的功能化。

  DOI：

  10.1021/acsmedchemlett.7b00039

文献信息

• Direct Identification of a Siderophore Import Protein Using Synthetic Petrobactin Ligands
  作者：Nikolas Bugdahn、Florian Peuckert、Alexander G. Albrecht、Marcus Miethke、Mohamed A. Marahiel、Markus Oberthür

  DOI：10.1002/anie.201005527

  日期：2010.12.27

  Nice catch! The immobilization of a synthetic petrobactin derivative on agarose was crucial for the isolation and identification of a bacterial siderophore import protein for the first time from crude cell extracts. The biochemical and genetic characterization of the identified protein confirmed that FpiA (YclQ) is the principal petrobactin importer in Bacillus subtilis.

  好赶上！合成石蜡蛋白衍生物在琼脂糖上的固定对于首次从粗细胞提取物中分离和鉴定细菌铁载体导入蛋白至关重要。鉴定出的蛋白质的生化和遗传学特征证实，FpiA（YclQ）是枯草芽孢杆菌中主要的岩石活化素进口商。
• Structure–activity relationship of lipid core peptide-based Group A Streptococcus vaccine candidates
  作者：Amy Chan、Waleed M. Hussein、Khairunnisa Abdul Ghaffar、Nirmal Marasini、Ahmed Mostafa、Sharareh Eskandari、Michael R. Batzloff、Michael F. Good、Mariusz Skwarczynski、Istvan Toth

  DOI：10.1016/j.bmc.2016.03.063

  日期：2016.7

  in a range of different illnesses, some of which are fatal. Currently, our efforts to develop a vaccine against GAS focuses on the lipid core peptide (LCP) system, a subunit vaccine containing a lipoamino acid (LAA) moiety which allows the stimulation of systemic antibody activity. In the present study, a peptide (J14) representing the B-cell epitope from the GAS M protein was incorporated alongside

  感染A组链球菌（GAS）可能导致一系列不同的疾病，其中一些是致命的。当前，我们开发抗GAS疫苗的工作集中在脂质核心肽（LCP）系统上，该系统是一种含有可刺激全身抗体活性的脂氨基酸（LAA）部分的亚单位疫苗。在本研究中，代表GAS M蛋白B细胞表位的肽（J14）与通用T辅助表位（P25）并入了四个具有不同空间方向或LAA长度的LCP构建体中。通过结构活性研究，发现虽然LCP方向的改变对免疫刺激的作用较弱，但在鼠模型中，构建体中LAA侧链长度的增加会增加抗体反应。此外，用先导LCP构建体免疫的小鼠在整个五个月的过程中也能够维持抗体活性。这些发现突出了LAA部分在鼻内肽疫苗开发中的重要性，并证实了其侧链长度对结构的免疫原性有影响。
• Novel green-yellow-orange-red light emitting donor-π-acceptor type dyes based on 1,3-indandione and dimedone moieties
  作者：Ilze Malina、Valdis Kampars、Baiba Turovska、Sergey Belyakov

  DOI：10.1016/j.dyepig.2017.01.017

  日期：2017.4

  Ten novel luminescent dyes containing 1,3-indandione or dimedone as electron acceptors, amino derivatives (dimethylamino, diphenylamino, julolidine and dibiphenylamino) as electron donor units and different length olefinic linkers (1-hydroxyallylidene or 1-hydroxypenta-2,4-dien-1-ylidene) are reported in this study. Newly synthesized compound structures are proven with X-ray analysis, 1H, 13C NMR spectroscopy

  十种新颖的发光染料，包含1,3-茚满二酮或二甲酮作为电子受体，氨基衍生物（二甲基氨基，二苯氨基，甲氧吡啶和二联苯氨基）作为电子供体单元和不同长度的烯烃接头（1-羟基亚烷基或1-羟基戊-2,4-二烯）在该研究中报道了-1-亚萘基）。X射线分析证明了新合成的化合物结构1 H，1313 C NMR光谱和元素分析。系统研究了这些染料的紫外可见吸收，发射，溶剂变色，溶剂荧光变色，氧化还原性质以及热稳定性和量子化学计算，以概述结构与性质之间的关系。这些染料在200°C以上具有适度的热分解温度，无显着的溶剂变色现象，正，显着的溶剂变色现象，较大的斯托克斯频移和绿色，黄色，橙色和红色发光，在非极性溶剂和稀溶液中的量子产率范围为0.03至0.93。电影。 量子化学计算（DFT）显示，所有染料均在2.77至3.22 eV之间显示出小的HOMO / LUMO缺口，这与实验数据相符。
• Total and Semisyntheses of Polymyxin Analogues with 2-Thr or 10-Thr Modifications to Decipher the Structure–Activity Relationship and Improve the Antibacterial Activity
  作者：Jian Li、Dongliang Guan、Feifei Chen、Weiwei Shi、Lefu Lan、Wei Huang

  DOI：10.1021/acs.jmedchem.0c02217

  日期：2021.5.13

  total and semisyntheses of a series of polymyxin analogues with 2-Thr and 10-Thr modifications to reveal the structure–activity relationship (SAR), which has not been fully elucidated previously. We employed two total-synthetic strategies to facilitate the diversified replacements on 2-Thr or 10-Thr, respectively. Moreover, semisynthetic approaches were utilized to achieve selective esterification

  本文中，我们报道了一系列具有2-Thr和10-Thr修饰的多粘菌素类似物的全部和半合成，以揭示结构-活性关系（SAR），此前尚未充分阐明。我们采用了两种全合成策略，分别促进了2-Thr或10-Thr的多样化替代。此外，使用半合成方法来实现2-Thr的选择性酯化或2-Thr和10-Thr的双重酯化。根据体外抗菌测定的结果，SAR分析表明，用带有疏水性侧链的氨基酸取代2- / 10-Thr可以维持抗铜绿假单胞菌的活性但对其他经过测试的革兰氏阴性细菌有不同的影响。2- / 10-Thr上的氨基乙酰基酯化具有优异的抗菌活性，化合物76对不同菌株的活性高2-8倍，对HK-2细胞系的毒性也较低。这项工作探讨了多粘菌素2- / 10-Thr的SAR，并为开发新型多粘菌素衍生物提供了有希望的策略。
• Dde-protected PNA monomers, orthogonal to Fmoc, for the synthesis of PNA–peptide conjugates
  作者：Laurent Bialy、Juan José Díaz-Mochón、Edgar Specker、Lise Keinicke、Mark Bradley

  DOI：10.1016/j.tet.2005.06.003

  日期：2005.8

  Herein the efficient solution phase synthesis of four novel 1-(4,4-dimethyl-2,6-dioxacyclohexylidene)ethyl/4-methoxytrityl (Dde/Mmt) protected PNA monomers is reported which were then used to synthesise PNA–peptide conjugates through a mild Dde deprotection strategy, which was fully orthogonal to Fmoc chemistry, allowing at will Fmoc peptide and Dde–PNA synthesis.

  可以说，肽核酸已成为最有趣的DNA模拟物之一。本文报道了四种新型的1-（4,4-二甲基-2,6-二氧杂环己基）乙基/ 4-甲氧基三苯甲基（Dde / Mmt）保护的PNA单体的有效溶液相合成，然后将其用于通过温和的Dde脱保护策略，与Fmoc化学完全正交，可随意合成Fmoc肽和Dde-PNA。