ethyl 2-[2-(triphenylmethylamino)-1,3-thiazole-4-carboxamido]-1,3-thiazole-4-carboxylate | 288590-36-3

• 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: ethyl 2-[2-(triphenylmethylamino)-1,3-thiazole-4-carboxamido]-1,3-thiazole-4-carboxylate
• 英文别名: ethyl-2-[2-(triphenylmethylamino)-1,3-thiazol-4-carboxamido]-1,3-thiazole-4-carboxylate；Ethyl 2-[[2-(tritylamino)-1,3-thiazole-4-carbonyl]amino]-1,3-thiazole-4-carboxylate
• CAS: 288590-36-3
• 化学式: C₂₉H₂₄N₄O₃S₂
• 分子量: 540.667
• InChiKey: MBYOTGUTPJRMLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 2-[2-(triphenylmethylamino)-1,3-thiazole-4-carboxamido]-1,3-thiazole-4-carboxylate 在 sodium hydroxide 、 三乙胺 、 三氟乙酸 作用下， 以 乙醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 2-[[2-[6-(Tritylamino)hexanoylamino]-1,3-thiazole-4-carbonyl]amino]-1,3-thiazole-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and evaluation of oligo-1,3-thiazolecarboxamide derivatives as HIV-1 reverse transcriptase inhibitors

  摘要：

  A set of oligo-1,3-thiazolecarboxamide derivatives able to interact with the minor groove of nucleic acids was synthesized. These oligopeptides contained different numbers of thiazole units presenting dimethylaminopropyl or EDTA moieties on the C-terminus, and aminohexanoyl or EDTA moieties on the N-terminus. The inhibition of such compounds on HIV-I reverse transcriptase activity was evaluated using different model template-primer duplexes: DNA DNA, RNA.DNA, DNA.RNA and RNA RNA. The biological properties of the thiazolecarboxamide derivatives were compared to those of distamycin, another minor groove binder which contains three pyrrole rings. Similar to distamycin, the thiazole containing oligopeptides were good inhibitors of the reverse transcription reaction in the presence of DNA.DNA. But in contrast to distamycin, the oligothiazolide derivatives were able to inhibit reverse transcription in the presence of RNA.DNA or DNA RNA template-primers. Both distamycin and oligothiazolecarboxamides had low affinity for RNA RNA duplexes. The inhibition obtained with the newly synthesized thiazolecarboxamides showed that these compounds were more powerful and versatile inhibitors of the RT-dependent polymerization than the natural minor groove binder distamycin. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00029-8
• 作为产物：
  描述：

  2-triphenylmethylamino-4-carboxy-1,3-thiazole 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 ethyl 2-[2-(triphenylmethylamino)-1,3-thiazole-4-carboxamido]-1,3-thiazole-4-carboxylate
  参考文献：
  名称：

  Synthesis and evaluation of oligo-1,3-thiazolecarboxamide derivatives as HIV-1 reverse transcriptase inhibitors

  摘要：

  A set of oligo-1,3-thiazolecarboxamide derivatives able to interact with the minor groove of nucleic acids was synthesized. These oligopeptides contained different numbers of thiazole units presenting dimethylaminopropyl or EDTA moieties on the C-terminus, and aminohexanoyl or EDTA moieties on the N-terminus. The inhibition of such compounds on HIV-I reverse transcriptase activity was evaluated using different model template-primer duplexes: DNA DNA, RNA.DNA, DNA.RNA and RNA RNA. The biological properties of the thiazolecarboxamide derivatives were compared to those of distamycin, another minor groove binder which contains three pyrrole rings. Similar to distamycin, the thiazole containing oligopeptides were good inhibitors of the reverse transcription reaction in the presence of DNA.DNA. But in contrast to distamycin, the oligothiazolide derivatives were able to inhibit reverse transcription in the presence of RNA.DNA or DNA RNA template-primers. Both distamycin and oligothiazolecarboxamides had low affinity for RNA RNA duplexes. The inhibition obtained with the newly synthesized thiazolecarboxamides showed that these compounds were more powerful and versatile inhibitors of the RT-dependent polymerization than the natural minor groove binder distamycin. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00029-8

文献信息

• Synthesis and evaluation of oligo-1,3-thiazolecarboxamide derivatives as HIV-1 reverse transcriptase inhibitors
  作者：Vladimir A. Ryabinin、Olga D. Zakharova、Ekaterina Y. Yurchenko、Olga A. Timofeeva、Igor V. Martyanov、Andrei A. Tokarev、Eugeny F. Belanov、Nikolai I. Bormotov、Laura Tarrago-Litvak、Marie Line Andreola、Simon Litvak、Georgy A. Nevinsky、Alexander N. Sinyakov

  DOI：10.1016/s0968-0896(00)00029-8

  日期：2000.5

  A set of oligo-1,3-thiazolecarboxamide derivatives able to interact with the minor groove of nucleic acids was synthesized. These oligopeptides contained different numbers of thiazole units presenting dimethylaminopropyl or EDTA moieties on the C-terminus, and aminohexanoyl or EDTA moieties on the N-terminus. The inhibition of such compounds on HIV-I reverse transcriptase activity was evaluated using different model template-primer duplexes: DNA DNA, RNA.DNA, DNA.RNA and RNA RNA. The biological properties of the thiazolecarboxamide derivatives were compared to those of distamycin, another minor groove binder which contains three pyrrole rings. Similar to distamycin, the thiazole containing oligopeptides were good inhibitors of the reverse transcription reaction in the presence of DNA.DNA. But in contrast to distamycin, the oligothiazolide derivatives were able to inhibit reverse transcription in the presence of RNA.DNA or DNA RNA template-primers. Both distamycin and oligothiazolecarboxamides had low affinity for RNA RNA duplexes. The inhibition obtained with the newly synthesized thiazolecarboxamides showed that these compounds were more powerful and versatile inhibitors of the RT-dependent polymerization than the natural minor groove binder distamycin. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Inhibition of HIV-1 integrase-catalysed reaction by new DNA minor groove ligands: the oligo-1,3-thiazolecarboxamide derivatives
  作者：Vladimir A. Ryabinin、Alexander N. Sinyakov、Vaea Richard de Soultrait、Anne Caumont、Vincent Parissi、Olga D. Zakharova、Elena L. Vasyutina、Ekaterina Yurchenko、Roman Bayandin、Simon Litvak、Laura Tarrago-Litvak、Georgy A. Nevinsky

  DOI：10.1016/s0223-5234(00)01181-8

  日期：2000.11

  Human immunodeficiency virus type 1 (HIV-1) integrase (IN) is an essential enzyme in the life cycle of the retrovirus, responsible for catalysing the insertion of the viral genome into the host cell chromosome. For this reason it provides an attractive target for antiviral drug design. We synthesized a series of novel thiazole (Tz)-containing oligopeptides (TCOs; oligo-1,3-thiazolecarboxamides), specifically interacting within the minor groove of DNA. The oligocarboxamide derivatives contained 1-4 Tz rings and different N- and C-terminal groups. The effect of these oligocarboxamides on the HIV-1 IN-catalysed reaction was investigated. Some of the compounds were able to inhibit the reaction. The inhibitory effect of the TCOs increased with the number of Tz units. The structure of various additional positively and/or negatively charged groups attached to the N- and C-termini of TCOs had a pronounced effect on their interaction with the DNA substrate complexed to IN. Modified TCOs having a better affinity for this complex should provide a rationale for the design of drugs targeting the integration step. (C) 2000 Editions scientifiques et medicales Elsevier SAS.