Research on heterocyclic compounds. XXI. Synthesis of imidazo[2,1-b]benzothiazole and imidazo[2,1-b]thiazole derivatives

The reaction of some 2-aminobenzothiazoles and 2-aminothiazoles with ethyl 3-bromo-4-oxopentanoate was investigated with the aim to obtain the corresponding imidazo[2,1-b]benzothiazole and imidazo[2,1-b]-thiazole derivatives, respectively. In some cases, two unexpected side products were obtained together with the required compound and their structures were elucidated: e.g., 2-aminobenzothiazole reacted with ethyl 3-bromo-4-oxopentanoate to give ethyl 2-methylimidazo[2,1-b]benzothiazole-3-acetate together with ethyl imi-dazo[2,1-b]benzothiazole-2-propionate and ethyl 3-(benzothiazol-2-yl)amino-4-oxopentanoate.     

Mass spectra of imidazo[2,1-b]thiazole and thiazolo[3,2-f]xanthene derivatives

The general principles of the mass-spectrometric disintegration of imidazo [2,1-b]thiazole and thiazolo[3,2-f]xanthene derivatives were established, and the characteristic fragments were identified. Disintegration proceeding with cleavage of the bonds in the thiazole ring of the 2(3)-ring system is characteristic of all of the investigated compounds. The cleavage of the S-C bonds, which are the weakest in the investigated systems, proceeds especially readily. Intense peaks of ions due to stepwise disintegration of the pyrimidine ring are also observed in the spectra of thiazoloxanthenes.     

Mass spectra of derivatives of imidazo[2,1-b] thiazole and thiazolo[3,2-a]benzimidazole

The mass spectra of 6-phenylimidazo[2,1-b]thiazole, thiazolo[3,2-a]benzimidazole, and a number of thiazole-ring-substituted derivatives were investigated. The fragmentation of both groups of compounds commences with cleavage of the bonds in the thiazole ring and leads to the appearance of nitrogen- and sulfur-containing fragments in the spectra. The common character of the mass spectrometric disintegration of the investigated compounds indicates that they have similar electronic structures. The mass number and position of a substituent in the thiazole ring can be determined on the basis of the mass numbers of a series of fragments.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 778–783, June, 1974.     

Protonation of imidazo[2,1-b]thiazole and thiazolo[2,3-f]purine

The protonation of imidazo[2,1-b]thiazole and thiazolo[2,3-f]purine was investigated by PMR spectroscopy. In CF₃COOH and D₂SO₄ the imidazothiazole forms a monocation, the structure of which corresponds to the addition of a proton to the nitrogen atom of the imidazole ring. In aqueous D₂SO₄ solutions, the thiazolopurine forms mono- and dications. The first protonation occurs at the nitrogen atom of the pyrimidine ring, while the second protonation occurs at the nitrogen atom of the imidazole ring. The effect of delocalization of the positive charge in the cations of the investigated compounds was examined.     

Nitrosation and bromination of 6-(2'-furyl)imidazo[2,1-b]thiazole and its derivatives

The action of nitrosating agents and bromine on 6-(2-furyl)imidazo[2,1-b]thiazole and its 3-methyl, 5-bromo, and 5-nitro derivatives was studied. The structures of the products were proved by UV, IR, and PMR spectroscopy and thin-layer chromatography.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1353–1358, October, 1972.     

苯并咪唑并[2,1-b]噻唑衍生物的合成

以2-巯基咪唑类化合物为原料,室温下与含有端基炔的二芳基高碘盐反应,一步合成苯并咪唑并[2,1-b]噻唑衍生物,其结构经¹H NMR、¹³C NMR、 单晶X-衍射和HR-MS表征。在最佳反应条件［n(2-巯基苯并咪唑)/n(二芳基高碘盐)=1/1,二氯甲烷为溶剂,反应12 h］下,目标化合物的产率最高为84%。同时对该反应的机理进行了详细探讨,并采用MTT法研究了目标化合物对人肝癌细胞（HepG2）生长情况的影响。结果表明：当浓度为4 μg/mL时,化合物3b具有较强的抑制HepG2细胞增殖的活性,抑制率为52%。     

Mannich bases and methiodides of 6-(2-furyl)imidazo[2,1-b]thiazole and its substituted derivatives

The Mannich reaction in a number of 6-(2-furyl)-substituted imidazo[2,1-b]thiazoles is realized initially in the 5 position of the imidazothiazole system, whereas it is also realized in the 5 position of the furan ring in the presence of excess reagents if the latter position is not substituted. Iodomethylation occurs at the N₇ atom of imidazothiazole. The Mannich bases of 6-(5-nitro-2-furyl)imidazo[2,1-b]thiazole are iodomethylated only at the aminomethyl group. The pK_a values of the series of compounds were measured.     

99mTc-radiolabeled imidazo[2,1-b]benzothiazole derivatives as potential radiotracers for glioblastoma

This study presents [^99mTc]BPTG-1 and [^99mTc]BPTG-2 for glioblastoma imaging. In vitro cellular uptakes of these radiotracers were examined in SKOV-3, MCF-7, U87-MG, HT-29, and A549 cell lines. U87-MG cell line displayed the highest radiotracers uptakes. Biodistribution study in U87-MG tumor bearing mice revealed higher uptake of radiotracers in tumor than muscle and brain. Liver, intestine, and kidneys displayed the highest radioactivity uptakes. The main route of radiotracers elimination was hepatobiliary. Due to the brain uptake of these radiotracers, they are promising radiotracers for future studies in the diagnosis of glioblastoma.

     

Pyrrolo[2,1-b]benzothiazole derivatives

A new method for obtaining pyrrolobenzothiazole derivatives, which can be used for the specific synthesis of polymethine dyes with predesignated properties, was developed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 549–553, April, 1991.     

Imidazo[2,1-b]benzothiazoles. II. Synthesis and antiinflammatory activity of some imidazo[2,1-b]benzothiazoles

3-[2-[p-(Un)substituted phenyl]imidazo [2,1-b]benzothiazol-3- yl]propionic acid derivatives (2a--e) were prepared via the interaction of the corresponding 2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazoles (1a--e) with acrylic acid in the presence of acetic anhydride and acetic acid. Esterification of 2a--e produced methyl esters (3a--e). Upon the interaction of 3a with m-chloroperbenzoic acid, the S-dioxide (4a) was obtained. Compound 5a was prepared from 4a by alkaline hydrolysis. Vilsmeier formylation for 1a--e produced novel [2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol-3- yl]formaldehyde derivatives (6a--e). Derivatives 6a--e reacted with ethyl bromoacetate to give ethyl 3-hydroxy-3-[2-[p-(un)substituted phenyl]imidazo[2,1-b]benzothiazol- 3-yl]propionate esters (7a--e). Compound dl-7a was resolved with l-(+)-tartaric acid. Compounds 2a--e showed weak or no activity in the carrageein-induced paw edema assay. Compound 4a significantly inhibited the leakage of pontamine-sky blue dye into the peritoneal cavity of mice, in the capillary permeability inhibition assay. Compound 5a inhibited the writhing by 62% in the acetic acid-induced writhing assay.     

Synthesis of benzo[4,5]imidazo[2,1-a]phthalazines

5,9-Disubstituted benzo[4,5]imidazo[2,1-a]phthalazines are synthesized efficiently from acylbenzoic acids and 2-nitro-5-chlorophenylhydrazine. Nucleophilic substitution in phthalazinones gave a variety of the title compounds after reduction and cyclization.     

The fluorescence spectroscopic study on the interaction between imidazo[2,1-b]thiazole analogues and bovine serum albumin

The interaction between imidazo[2,1-b]thiazole (IMTZ) and bovine serum albumin (BSA) was analyzed by fluorescence and ultraviolet spectroscopy at 302 and 310 K under simulative physiological conditions. The results show that IMTZ can effectively quench the intrinsic fluorescence of BSA via static and dynamic quenching. The binding constant, binding sites of IMTZ with BSA were calculated. According to the F?rster non-radiation energy transfer theory, the average binding distance between IMTZ and BSA was obtained. What's more, the synchronous fluorescence spectra indicated that the conformation of BSA has been changed. The results provided the information for the binding of IMTZ to BSA, and the influences of substituent group on the interaction were also discussed.     

Synthesis and X-ray structure of new spiro-imidazo[2,1-b]thiazole

Spiro[5,5]undecane-3-one 1 was converted to 4 ,7-dihydrospiro[benzo[d]thiazole-6(5H),1′-cyclohexane]-2-amine 3 , which is condensed with bromomethyl (halo)phenyl ketones and cyclized to compounds 5a-5c . The X-ray crystallography of the 5b reveals that formation route for 5 is via 3-position-substituted-spiro-iminothiazole 4 .     

Efficient route to benzo[4,5]imidazo[2,1-a]phthalazines

Benzo[4,5]imidazo[2,1-a]phthalazines have been obtained from various o-nitrophenylhydrazines through different 2-(2-nitrophenyl)-1,2-dihydro-1-phthalazinones as intermediates using an elaborated advanced procedure. An activated chlorine atom in 2-nitrophenyl moiety of the latter is able to undergo nucleophilic substitution for secondary alicyclic amines yielding novel substituted phthalazinones. Their one-pot reduction and cyclodehydration yield a series of novel substituted benzo[4,5]imidazo[2,1-a]phthalazines.