DIETHYL1-BENZYL-4-PHENYL-1,4-DIHYDROPYRIDINE-3,5-DICARBOXYLATE锛圵S201542锛,WUXIAPPTEC" | 120533-76-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: DIETHYL1-BENZYL-4-PHENYL-1,4-DIHYDROPYRIDINE-3,5-DICARBOXYLATE锛圵S201542锛,WUXIAPPTEC"
• 英文名称: diethyl 1-benzyl-1,4-dihydro-4-phenylpyridine-3,5-dicarboxylate
• 英文别名: diethyl 1-benzyl-4-phenyl-1,4-dihydropyridine-3,5-dicarboxylate；BML-278；MC2562；diethyl 1-benzyl-4-phenyl-4H-pyridine-3,5-dicarboxylate
• CAS: 120533-76-8
• 化学式: C₂₄H₂₅NO₄
• 分子量: 391.467
• InChiKey: JOHFECBOWRGWJZ-UHFFFAOYSA-N

物化性质

• 熔点：
  139-141 °C(Solv: cyclohexane (110-82-7); benzene (71-43-2))
• 沸点：
  525.5±50.0 °C(Predicted)
• 密度：
  1.183±0.06 g/cm3(Predicted)
• 溶解度：
  溶于DMSO（高达5mg/ml）。

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  5

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：

  DIETHYL1-BENZYL-4-PHENYL-1,4-DIHYDROPYRIDINE-3,5-DICARBOXYLATE锛圵S201542锛,WUXIAPPTEC" 以 四氢呋喃 、 甲醇 为溶剂， 以38.1%的产率得到tetraethyl 3,9-dibenzyl-6,12-diphenyl-3,9-diazapentacyclo[6.4.0.0^2,7.0^4,11.0^5,10]dodecane-1,5,7,11-tetracarboxylate
  参考文献：
  名称：

  Design, Synthesis and Biological Evaluation of 3,9-diazatetraasteranes as Novel Matrilysin Inhibitors

  摘要：

  Matrilysin is an ideal biological target to develop novel inhibitors because it is overexpressed in malignant tumour cells. A series of 3,9‐diazatetraasteranes was designed as inhibitors of matrilysin, which was an ideal biological target because it is responsible for aggressive malignant phenotypes and poor prognoses implicated in many cancers. Docking simulation supported the initial pharmacophore hypothesis and suggested a common interaction mechanism of 3,9‐diazatetraasteranes with the catalytic site of matrilysin. The 3,9‐diazatetraasteranes were synthesized by the photocyclization of 4‐aryl‐1,4‐dihydropyridines, and their structures were determined using 1H NMR, 13C NMR and MS. The inhibitory activities of these compounds on matrilysin were investigated in vitro using an MTT assay in A549 (small cell lung cancer) cells. The results show that the 3,9‐diazatetraasteranes can inhibit the growth of A549 tumour cells. The best IC50 value is approximately 50 μm. This result indicates that 3,9‐diazatetraasteranes will be useful pharmacological tools for the investigation of matrilysin inhibitors.

  DOI：

  10.1111/cbdd.12185
• 作为产物：
  描述：

  tetraethyl 1,5-dibenzyl-1,5,8,8bα-tetrahydro-4,8-diphenylcyclobuta[1,2-b:3,4-b']dipyridine-3,4aα,7,8aβ(4H,4bβH)-tetracarboxylate 以 四氢呋喃 、 甲醇 为溶剂， 反应 336000.0h， 以33%的产率得到DIETHYL1-BENZYL-4-PHENYL-1,4-DIHYDROPYRIDINE-3,5-DICARBOXYLATE锛圵S201542锛,WUXIAPPTEC"
  参考文献：
  名称：

  4-芳基-1,4-二氢吡啶的溶液二聚

  摘要：

  在λ≥270 nm处照射时，4-芳基-1,4-二氢吡啶1的溶液除了少量的抗二聚体3以外，还以笼型二聚体2为主要产物。1 H-NMR数据和X射线晶体结构证明了具有轴向取向的4-芳基取代基的两个二聚体的中心对称性质。滤光（λ> 313 nm）的照射导致合成和反二聚体4和3的收率几乎相等。事实证明，在未经过滤的光照射下，抗二聚体3的收率很低，这是由于部分裂解返回至其单体原料所致1。

  DOI：

  10.1002/(sici)1099-0690(200001)2000:2<245::aid-ejoc245>3.0.co;2-2

文献信息

• Synthesis of 1,4-Dihydropyridines and Their Fluorescence Properties
  作者：Shunsuke Sueki、Ryo Takei、Yuto Zaitsu、Junya Abe、Akane Fukuda、Keisuke Seto、Yukio Furukawa、Isao Shimizu

  DOI：10.1002/ejoc.201402426

  日期：2014.8

  We have successfully synthesized 3,4,5-substituted 1,4-dihydropyridines (1,4-DHPs) from amine hydrochloride salts, aldehydes, and acetals in good yields without the addition of a catalyst. The synthesized 1,4-DHPs exhibit various wavelengths of fluorescence, which could be tuned by changing the substituents at the 3- and 5-positions of the 1,4-DHPs.

  我们已经成功地从胺盐酸盐、醛和缩醛中合成了 3,4,5-取代的 1,4-二氢吡啶 (1,4-DHPs)，且收率良好，无需添加催化剂。合成的 1,4-DHPs 显示出不同波长的荧光，可以通过改变 1,4-DHPs 3-和 5-位的取代基来调节。
• Study of 1,4-Dihydropyridine Structural Scaffold: Discovery of Novel Sirtuin Activators and Inhibitors
  作者：Antonello Mai、Sergio Valente、Sarah Meade、Vincenzo Carafa、Maria Tardugno、Angela Nebbioso、Andrea Galmozzi、Nico Mitro、Emma De Fabiani、Lucia Altucci、Aleksey Kazantsev

  DOI：10.1021/jm9008289

  日期：2009.9.10

  deacetylases have emerged as potential therapeutic targets for treatment of human illnesses such as cancer, metabolic, cardiovascular, and neurodegenerative diseases. The benefits of sirtuin modulation by small molecules have been demonstrated for these diseases. In contrast to the discovery of inhibitors of SIRT1, -2, and -3, only activators for SIRT1 are known. Here, we rationalized the potential of

  NAD +依赖的沉默调节蛋白脱乙酰基酶已经成为治疗人类疾病如癌症，代谢，心血管和神经退行性疾病的潜在治疗靶标。对于这些疾病，已经证明了通过小分子调节瑟土因的益处。与SIRT1，-2和-3抑制剂的发现相反，仅SIRT1的激活剂是已知的。在这里，我们在合理化显影沉默调节蛋白的配体的前所未见的二氢吡啶骨架的电位，因此，我们制备了一系列1,4-二氢吡啶基衍生物的1 - 3。对它们的SIRT1-3脱乙酰基酶活性的评估表明，二氢吡啶结构的N1位上的取代基对Sirtuin活性的重要性。环丙基，苯基或苯乙基位于N1处赋予了非选择性SIRT1和SIRT2抑制活性，而苄基位于N1处赋予了有效的SIRT1，-2和-3激活。用小鼠C2C12成肌细胞进行的hMSC和线粒体功能研究进行的衰老分析证实了该化合物的新颖独特的SIRT激活特性。
• One-Pot Synthesis of N-Substituted 4-Aryl-1,4-dihydropyridines Under Solvent-Free Conditions and Microwave Irradiation
  作者：Saeed Balalaie、Elahe Kowsari

  DOI：10.1007/s007060170012

  日期：2001.12

   The three-component condensation of benzaldehyde derivatives, alkyl propiolates, and primary amines catalyzed by silica gel, zeolite HY, montmorillonite K-10, and acidic alumina under microwave irradiation gave N-substituted 4-aryl-1,4-dihydropyridines in short reaction times and high yields. The best results were obtained with silica gel.

  硅胶，HY沸石，蒙脱土K-10和酸性氧化铝在微波辐射下催化苯甲醛衍生物，丙酸烷基酯和伯胺的三组分缩合反应，在短时间内反应得到N-取代的4-芳基-1,4-二氢吡啶时间和高产量。使用硅胶可获得最佳结果。
• Synthesis and biological evaluation of first N-alkyl syn dimeric 4-aryl-1,4-dihydropyridines as competitive HIV-1 protease inhibitors
  作者：A Hilgeroth

  DOI：10.1016/s0223-5234(01)01228-4

  日期：2001.4

  A first series of novel N-alkyl substituted syn dimeric 4-aryl-1,4-dihydropyridines 12--17 have been synthesised and evaluated as HIV-1 protease inhibitors in in vitro assays. While the N-methyl derivatives 12 and 13 were almost inactive, with IC(50)-values of about 225 microM, the N-benzyl compounds with varied ester groups all exhibited stronger activities, with IC(50)-values of 11--12 microM for

  已经合成了第一系列的新颖的N-烷基取代的同工二聚体4-芳基-1，4-二氢吡啶12--17，并在体外测定中评价为HIV-1蛋白酶抑制剂。尽管N-甲基衍生物12和13几乎没有活性，IC（50）值约为225 microM，但具有不同酯基的N-苄基化合物均表现出较强的活性，IC（50）值为11--目前具有乙基酯功能的最佳化合物16和17为12 microM。新型抑制剂对HIV-1蛋白酶的抑制作用具有竞争性。随着观察到的从N-甲基衍生物到N-苄基化合物的活性的增加，结合模式可能对应于具有四个芳香族残基与HIV-1的S1 / S1'和S2 / S2'区的疏水相互作用的环状脲蛋白酶。
• Synthesis and Biological Evaluation of the First <i>N</i>-Alkyl Cage Dimeric 4-Aryl-1,4-dihydropyridines as Novel Nonpeptidic HIV-1 Protease Inhibitors
  作者：Andreas Hilgeroth、Michael Wiese、Andreas Billich

  DOI：10.1021/jm991115k

  日期：1999.11.1

  A first series of novel NH and N-alkyl-substituted cage dimeric 4-aryl-1,4-dihydropyridines 3a-f has been synthesized and evaluated as HIV-1 protease inhibitors in in vitro assays. While the NH and N-methyl derivatives 3a,b,e,f were almost inactive with IC(50) values of about 200 microM, the N-Benzyl compounds exhibited stronger activity with an IC(50) value of 16.2 microM for the presently best compound

  已经合成了第一系列的新颖的NH和N-烷基取代的笼二聚体4-芳基-1，4-二氢吡啶3a-f，并在体外测定中评价为HIV-1蛋白酶抑制剂。尽管NH和N-甲基衍生物3a，b，e，f几乎没有活性，IC（50）值约为200 microM，但目前，N-苄基化合物显示出更强的活性，IC（50）值为16.2 microM。最佳化合物3c。这些新型抑制剂对HIV-1蛋白酶的抑制作用具有竞争性。随着观察到的分别从NH和N-甲基衍生物到N-苄基化合物的活性的增加，结合方式可能对应于环状和氮杂脲的结合方式，显示出四个芳族残基与S1 / S1'和S2 /的疏水相互作用HIV-1蛋白酶的S2'区。