Molecular Design, Syntheses, and Utilization of New Thiazole-Related Compounds

新型噻唑相关化合物的分子设计、合成和利用

• 批准号: 14370723
• 负责人: NAGAO Yoshimitsu
• 金额: $ 8.38万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370723/
• 关键词: thiazole; thiadiazole; nonbonded interaction; X-ray analysis; DFT-calculation; acetazolamide; stromelysin; antibiotic; 抗体標識試薬; ルシフェリン; DFT計算

In the course of studies on molecular design, syntheses, and utilization of thiazole-related compounds, we have developed several new heterocyclic compounds involving intramolecular nonbonded S【triple bond】X (X = O, N, S, halogens) interactions and new syntheses of pharmaceutically interesting compounds. In each X-ray crystallographic structure of 2-(furan or thiophen-2-yl)1, 3 thiazole, chemospecific nonbonded O 【triple bond】 S or S 【triple bond】 N interaction was observed. We have synthesized a model compound of firefly luciferin and mono-, bi-, and tri-thiazole derivatives, in which the existence of each nonbonded S 【triple bond】 N interaction was confirmed by their X-ray crystallographic analyses. The DFT calculation of their model molecules could support that the molecule bearing such an S【triple bond】N interaction was most stable in relative energy among several ones. The first nonbonded S【triple bond】X(X = F, Cl, Br, I ) interactions in four kinds of 2-(2-halophenyl)-1, 3thiazole derivatives have been demonstrated in a same manner as described above. Interestingly, a tri-thiazole derivative exhibited considerable anticancer activities against some human cancer cells in vitro. The nonbonded S 【triple bond】 O interaction in the crystalline structures of diuretic acetazolamide and stromelysin-inhibitors, thiadiazolinethiones, was similarly observed even in their complex structures with carbonic anhydrase I and II and stromelysin. The pendant molecule (mercaptoazetidinyl thiazoline) of a new oral carbapenem antibiotic was efficiently synthesized by using azabicyclobutane. The antibody labeled with a new infrared fluorescent-labeling agent (indocyanine-green-acylthiazolidinethione ) was utilized for diagnosing microcancers

在研究与噻唑相关化合物的分子设计，合成和利用的研究过程中，我们开发了几种涉及分子内无键的S【x（x = o，x = o，n，n，s，halogens）相互作用的新型杂环化合物，并具有有趣的化合物。在每个X射线晶体学结构中，观察到2-（Furan或硫代-2-基）1，3噻唑，化学种以化学的非键O【三键或ss【三键n相互作用。我们已经合成了萤火虫荧光素和单，双噻唑和三唑衍生物的模型化合物，其中每个非键的S【三键n相互作用都通过其X射线晶体学分析证实。它们的模型分子的DFT计算可以支持，具有这种s的三键相互作用的分子在几种相对能量中最稳定。第一个非键S [三键] x（x = f，cl，br，i）以四种2-（2- 2甲基苯基）-1的相互作用以与上述方式相同的方式证明。有趣的是，三噻唑衍生物在体外对某些人类癌细胞表现出相当大的抗癌活性。同样观察到了利尿剂乙酰唑胺抑制剂（硫代二唑烷二酮）在晶体结构中的无键S [三键] O相互作用，即使在其与碳酸酐酶I和II和II和Stromelysin的复杂结构中也观察到了它们的复杂结构。通过使用偶氮环丁烷有效合成了一种新的口服碳烯抗生素的吊坠分子（胃氮二氨基噻唑啉）。用新红外荧光标签剂（吲哚羟氨酸 - 酰基硫乙烯二世）标记的抗体用于诊断微量升流

项目成果

Yoshimitsu Nagao et al.: "A New Infrared Fluorescent-Labeling Agent and Labeled Antibody for Diagnosing Microcancers"Bioorg.& Med.Chem.. 11. 3289-3294 (2003)

Yoshimitsu Nagao 等：“用于诊断微癌的新型红外荧光标记剂和标记抗体”Bioorg。

Yoshimitsu Nagao: "Remarkable Discrepancy in the Predominant Structures of Acyl(or thioacyl) amino-thiadlazoles, Acyl(or thioacyl)aminooxadiazoles and Related Compounds"Tetrahedron Lett.. 43・9. 1709-1712 (2002)

Yoshimitsu Nagao：“酰基（或硫酰基）氨基噻二唑、酰基（或硫酰基）氨基恶二唑及相关化合物的主要结构的显着差异”Tetrahedron Lett.. 1709-1712（2002）

Yoshimitsu Nagao et al.: "Cyclization, Ring-Expansion, and Several Cascade Reactions Utilizing Allenylic Molecular Structure Characteristics"J.Synth.Org.Chem.Jpn.. 61(11). 1088-1098 (2003)

Yoshimitsu Nagao 等人：“利用烯烯型分子结构特征的环化、环扩展和几个级联反应”J.Synth.Org.Chem.Jpn.. 61(11)。

Yoshimitsu Nagao: "Development of New Reactions and Their Pharmaceutical Application Based on the Molecular Structure Characteristics"Yakugaku Zassi. 122(1). 1-27 (2002)

永尾义光：“基于分子结构特征的新反应的开发及其药物应用”Yakugaku Zassi。

Yoshimitsu Nagao: "Development of New Reactions and Their Pharmaceutical Application Based on the Molecular Structure Characteristics"Yakugaku Zasshi. 122・1. 1-27 (2002)

长尾义光：“基于分子结构特征的新反应的开发及其药物应用”Yakugaku Zasshi 122・1（2002）。