N¹-(triphenylmethyl)-1,3-diaminopropane | 112655-56-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N¹-(triphenylmethyl)-1,3-diaminopropane
• 英文别名: N¹-trityl-1,3-diaminopropane；N-(triphenylmethyl)propane-1,3-diamine；N1-tritylpropane-1,3-diamine；N-tritylpropane-1,3-diamine；3-tritylaminopropylamine；N-Tritylpropylenediamine；N'-tritylpropane-1,3-diamine
• CAS: 112655-56-8
• 化学式: C₂₂H₂₄N₂
• 分子量: 316.446
• InChiKey: ILJLWSUNJBOTCX-UHFFFAOYSA-N

物化性质

• 沸点：
  457.2±40.0 °C(Predicted)
• 密度：
  1.073±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N¹-(triphenylmethyl)-1,3-diaminopropane 在 sodium hydroxide 、 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 生成 5,10-Bis(mesitylenesulfonyl)-1-triphenylmethyl-1,5,10-triazatridecane
  参考文献：
  名称：

  A Comparison of Structure−Activity Relationships between Spermidine and Spermine Analogue Antineoplastics

  摘要：

  A systematic investigation of the impact of spermidine analogues both in vitro and in vivo is described. The study characterizes the effects of these analogues on L1210 cell growth, polyamine pools, ornithine decarboxylase, S-adenosyl-L-methionine decarboxylase, spermidine/spermine N-1-acetyltransferase, the maintenance of cellular charge, i.e., cationic equivalence associated with the polyamines and their analogues, and compares their ability to compete with spermidine for transport. The findings clearly demonstrate that the activity of-the linear polyamine analogues is highly dependent on the length of the triamines and the size of the N-alpha,N-omega-substituents. It appears that there is an optimum chain length for various activities and that the larger the N-alpha,N-omega-alkyls, the less active the compound. Metabolic transformation including N-dealkylation of these compounds is also evaluated. While there is no monotonic relationship between chain length and the ability of the analogue to be metabolized, the dipropyl triamines are clearly more actively catabolized than the corresponding methyl and ethyl systems. A comparison of the triamines with the corresponding tetraamines is made throughout the text regarding both in vitro activity against L1210 cells and in vivo toxicity measurements, suggesting that several triamine analogues may offer therapeutic advantages over the corresponding tetraamines.

  DOI：

  10.1021/jm960849j
• 作为产物：
  描述：

  在 哌啶 作用下， 以 甲醇 为溶剂， 以249 mg的产率得到N¹-(triphenylmethyl)-1,3-diaminopropane
  参考文献：
  名称：

  Triphenylbutanamines: Kinesin Spindle Protein Inhibitors with in Vivo Antitumor Activity

  摘要：

  The human mitotic kinesin Eg5 represents a novel mitotic spindle target for cancer chemotherapy. We previously identified S-trityl-L-cysteine (STLC) and related analogues as selective potent inhibitors of Eg5. We herein report on the development of a series of 4,4,4-triphenylbutan-1-amine inhibitors derived from the STLC scaffold. This new generation systematically improves on potency: the most potent C-trityl analogues exhibit K-i(aPP) <= 10 nM and GI(50) approximate to 50 nM, comparable to results from the phase II clinical benchmark ispinesib. Crystallographic studies reveal that they adopt the same overall binding configuration as S-trityl analogues at an allosteric site formed by loop L5 of Eg5. Evaluation of their druglike properties reveals favorable profiles for future development and, in the clinical candidate ispinesib, moderate hERG and CYP inhibition. One triphenylbutanamine analogue and ispinesib possess very good bioavailability (51% and 45%, respectively), with the former showing in vivo antitumor growth activity in nude mice xenograft studies.

  DOI：

  10.1021/jm201195m

文献信息

• Discovery of a 3,4,5-trisubstituted-1,2,4-triazole agonist with high affinity and selectivity at the somatostatin subtype-4 (sst₄) receptor
  作者：Iman Daryaei、Karin Sandoval、Ken Witt、Maria Kontoyianni、A. Michael Crider

  DOI：10.1039/c8md00388b

  日期：——

  at sst4. The 1,2,4-triazoles containing an aminopropyl group at position-4 showed enhanced binding affinity compared to the 3-position. One compound with an 3-(imidazol-4-yl)propyl group at position-4 (compound 44) imparted high affinity and selectivity at sst4 (sst2A = >10 000 nM; sst4 = 19 nM), acting as an agonist (EC50 = 6.8 nM). Docking 44 into a model-built structure of sst4 pointed to differences

  合成了一系列含有 1,2,4-三唑部分的化合物，靶向生长抑素受体亚型 4 (sst 4 )。开发了其中 Phe 6 /Phe 7 /Phe 11、Trp 8和 Lys 9模拟基团在 1,2,4-三唑环的 3、4 和 5 位互换的化合物。在3位上含有2-(咪唑-4-基)乙基取代基的1,2,4-三唑在sst 4处表现出中等的结合亲和力。在5位上含有(吲哚-3-基)甲基取代基的1,2,4-三唑在sst 4处缺乏亲和力。与 3 位相比，4 位含有氨丙基的 1​​,2,4-三唑显示出增强的结合亲和力。一种在 4 位具有 3-(咪唑-4-基) 丙基的化合物 (化合物44 ) 在 sst 4处具有高亲和力和选择性(sst 2A = >10 000 nM; sst 4 = 19 nM)，充当激动剂（EC 50 = 6.8 nM）。将44对接到 sst 4的模型构建结构中表明其与其他低亲和力化合物的结合存在
• Direct Asymmetric Aldol Reaction of 5<i>H</i>-Oxazol-4-ones with Aldehydes Catalyzed by Chiral Guanidines
  作者：Tomonori Misaki、Gouta Takimoto、Takashi Sugimura

  DOI：10.1021/ja101216x

  日期：2010.5.12

  A new chiral bicyclic guanidine-catalyzed direct catalytic aldol reaction of 5H-oxazol-4-ones with aldehydes has been developed. The present aldol reaction proceeds smoothly with high enantioselectivity using bicyclic guanidines bearing a hydroxy group at the appropriate position, and various combinations of 5H-oxazol-4-ones and aldehydes are applicable. The method provides synthetically useful alpha

  开发了一种新的手性双环胍催化 5H-恶唑-4-酮与醛的直接催化醛醇反应。使用在适当位置带有羟基的双环胍，本醛醇反应以高对映选择性顺利进行，并且5H-恶唑-4-酮和醛的各种组合是适用的。该方法提供了在α-碳原子处带有手性四元立体中心的合成有用的α，β-二羟基羧酸盐。
• General Approach for the Liquid-Phase Fragment Synthesis of Orthogonally Protected Naturally Occurring Polyamines and Applications Thereof
  作者：Stefania Kalantzi、Constantinos M. Athanassopoulos、Raili Ruonala、Yrjo Helariutta、Dionissios Papaioannou

  DOI：10.1021/acs.joc.9b02066

  日期：2019.12.6

  Orthogonally protected polyamines (PAs) have been synthesized using α,ω-diamines and ω-aminoalcohols as N-Cx-N and N-Cy synthons, respectively, and the Mitsunobu reaction as the key reaction for the assembly of the PA skeleta. The Trt, Dde, and Phth groups have been employed for protecting the primary amino functions and the Ns group for activating the primary amino functions toward alkylation and

  已经使用 α,ω-二胺和 ω-氨基醇分别作为 N-Cx-N 和 N-Cy 合成子合成了正交保护的多胺 (PA)，并且 Mitsunobu 反应是 PA 骨架组装的关键反应。Trt、Dde 和 Phth 基团已用于保护伯氨基功能，Ns 基团用于激活伯氨基功能以实现烷基化和仲氨基功能保护。该方法很容易扩展以适应蜘蛛毒素 Agel 416 和 HO-416b 的全合成，分别包含 3-4-3-3 和 3-3-3-4 PA 骨架。
• Design, synthesis and evaluation of novel uracil acetamide derivatives as potential inhibitors of Plasmodium falciparum dUTP nucleotidohydrolase
  作者：Orla McCarthy、Alex Musso-Buendia、Marcel Kaiser、Reto Brun、Luis M. Ruiz-Perez、Nils Gunnar Johansson、Dolores Gonzalez Pacanowska、Ian H. Gilbert

  DOI：10.1016/j.ejmech.2008.05.018

  日期：2009.2

  inhibitors of the enzyme can be designed and synthesised with the aim of being developed into novel anti-parasitic drugs. Analogue based design was used to target the Plasmodium falciparum dUTPase (PfdUTPase). The structures of previously discovered selective inhibitors of the PfdUTPase were modified by insertion of an amide bond. A series of tritylated uracil acetamide derivatives were synthesised

  普遍存在的酶dUTP核苷酸水解酶（dUTPase）催化dUTP水解为dUMP，可以被视为抵制尿嘧啶掺入DNA的第一道防线。抑制这种酶会导致尿嘧啶过度掺入DNA中，导致DNA片段化和细胞死亡，因此具有致死性。通过利用人和疟原虫dUTPase之间的结构差异，可以设计和合成该酶的选择性抑制剂，以开发为新型抗寄生虫药物。基于类似物的设计用于靶向恶性疟原虫dUTPase（Pf dUTPase）。先前发现的Pf选择性抑制剂的结构dUTPase通过插入酰胺键进行修饰。合成了一系列三苯甲基化的尿嘧啶乙酰胺衍生物，并评价了其对体外酶和寄生虫生长的抑制作用。这些化合物是Pf dUTPase的弱抑制剂。
• Selective binding of imidazoles and related organic molecules in an organic solvent
  作者：Jeremy D. Kilburn、A. Roderick. MacKenzie、W. Clark. Still

  DOI：10.1021/ja00212a058

  日期：1988.2

  Synthese d'un derive de dioxatetraaza [11.10] paracyclophane avec un pont carbonyle (formant une imidazolidone-2) et un pont m-xylylenediamino; complexes avec divers heterocycles azotes

  Synthese d'un衍生 de dioxatetraaza [11.10] paracyclophane avec un pont carbonyle (formant une imidazolidone-2) et un pont m-xylylenediamino; 复合物 avec divers 杂环 azotes