Synthesis and Antitumor Evaluation of New Thiazolo[5,4-b]quinoline Derivatives

Abstract

A new synthesis of 9-hydroxy- and 9-(alkylamino)thiazolo[5,4-b]quinolines by cyclization of 4-(ethoxycarbonyl)-5-(arylamino)thiazoles and 5-(arylamino)-4-carbamoylthiazoles, respectively, is described. In vitro cytotoxicity of a large number of derivatives of these compounds has been tested against several cell lines. The highest activities observed are associated with the presence of a 2-[[(N,N-diethylamino)ethyl]amino] substituent at C-2 and a fluorine atom at the C-7 position of the tricyclic planar heteroaromatic framework. Three structural features seem to be essential for antitumor activities: a positive charge density at carbon C-7, a side chain at position C-2 or C-9 of the thiazoloquinoline skeleton with two basic nitrogens and a pKa value of 7.5-10 in the most basic center, and a conformational flexibility of this basic side chain. These structural requirements must be simultaneously satisfied in order to ensure a significant antitumor activity.

Metal-Free One-Pot Four-Component Cascade Annulation in Ionic Liquids at Room Temperature: Convergent Access to Thiazoloquinolinone Derivatives

“…Initially, the model reaction was carried out with equimolar amounts of the abovementioned four partners without any solvent and catalyst at room temperature. We did not observe the trace of the desired product 5aa, even after 24 h of stirring, and the starting materials remained completely unreacted ( 6). In all reactions, most of the reactants remained unconsumed.…”

“…Over the years, chemists have devoted their efforts toward the development of operationally simple and sustainable strategies to assemble heterocyclic systems, which are frequently encountered scaffolds in numerous natural products, drugs, and pharmaceutically significant substances. , Among polycyclic heterocycles, the thiazoloquinoline scaffold is a notable template in medicinal chemistry, and its derivatives possess useful biological and pharmacological properties . Some thiazoloquinoline derivatives have been described as potential anti-inflammatory, antispasmodics, probes for fluorescent molecules, and precursors of symmetrical cyanines . Moreover, thiazoloquinoline is also found to be active in the production of polymethine dyes and as spectral sensitizers of silver halide emulsions …”

“…5 Some thiazoloquinoline derivatives have been described as potential anti-inflammatory, antispasmodics, probes for fluorescent molecules, and precursors of symmetrical cyanines. 6 Moreover, thiazoloquinoline is also found to be active in the production of polymethine dyes and as spectral sensitizers of silver halide emulsions. 7 Literature reports for the construction of thiazoloquinolinone derivatives involve hydration/cyclodehydration of 3substituted 2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl-thiocyanates via thiocarbamates 8a and a palladium-catalyzed reaction of ethyl 2-bromo-5-chlorothiazole-4-carboxylate with arylboronic acids.…”

Synthesis and Antiproliferative Evaluation of Certain Indeno[1,2-c]quinoline Derivatives. Part 2

“…[29][30][31][32][33][34] Similar approaches to these compounds were also reported where the benzene moiety was isosterically replaced with a thiazole ring. 35,36 Camptothecin (CPT, 37,38 Chart 1), an alkaloid isolated from Camptotheca acuminata, and its derivatives such as topotecan and irinotecan are prototypical topo I inhibitors and currently used as anticancer drugs. However, the chemically unstable lactone ring limited their clinical utility.…”

Synthesis and Cytotoxic Evaluation of Novel Thiazolocarbazoles. Part II1

“…The thiazole ring is present in various marine or terrestrial natural compounds and a number of structure-activity studies have already been made to determine the essential structural requirements associated with its biological activity. 2 -4 In connection with recent works on the interest aroused by thiazoloacridines (I) 5 -7 , thiazoloquinolines (II) 8 and substituted benzothiazoles (III) 9,10 , we recently described the synthesis of new derivatives in which the thiazole ring was fused with various heterocyclic structures (IV, V) 11,12 . As a continuation of this work, we recently decided to prepare novel linear tetracyclic thiazolocarbazoles (VI, VII) derivatives by fusing the carbazole and the thiazole rings 1,13 (Fig.…”