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

在对噻唑类化合物的分子设计、合成和利用的研究过程中，我们开发了几个新的杂环化合物，涉及分子内非键S[三键]X(X=O，N，S，卤素)相互作用和新的药用活性化合物的合成。在2-(呋喃或噻吩基)1，3-噻唑的每个X射线晶体结构中，观察到化学专一性的非键O[三键]S或S[三键]N相互作用。我们合成了萤火虫荧光素与单、双、三噻唑类化合物的模型化合物，其中每个非键S[三键]N相互作用的存在被X-射线晶体分析所证实。对其模型分子的密度泛函计算表明，在几种分子中，具有这种S[三键]N相互作用的分子相对能量最稳定。用同样的方法证明了四种2-(2-卤苯基)-1，3-噻唑类化合物中的第一个非键S[三键]X(X=F，Cl，Br，I)相互作用。有趣的是，一种三噻唑衍生物在体外对一些人类癌细胞表现出相当大的抗癌活性。利尿剂乙酰唑胺和基质分解酶抑制剂噻二唑硫酮晶体结构中的非键合S[三键]O相互作用类似，甚至在它们与碳酸氢酶I和II以及基质分解素的复杂结构中也观察到类似的相互作用。以氮杂环丁烷为原料，高效地合成了一种新型口服碳青霉烯类抗生素的侧链分子(硫代氮杂二基噻唑啉)。用一种新的红外荧光标记剂(吲哚青绿-酰基噻唑硫酮)标记的抗体用于诊断微癌

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