Band 19, Heft 2

1,2-Azoles comprising pyrazoles, isoxazoles, and isothiazoles have occupied a distinctive position in the design and synthesis of novel biologically active compounds that exert remarkable pharmaceutical activities as medicines and agrochemicals. As a consequence, there has been an increasing interest among synthetic organic/medicinal chemists in the development of methodologies for the rapid access to these heterocycles. In this review, we have summarized the most significant advances in the construction of functionalized pyrazoles, isoxazoles, and isothiazoles reported in the literature up to 2012.

The attractiveness of heterocyclic compounds in medicinal chemistry has increased significantly in the past few decades as they have been proven to be highly active for a number of purposes. More specifically, the benzothiazole-containing heterocyclic compounds have shown great promise in the pharmaceutical industry. As continuation of our first review article of the synthesis and specific applications of various benzothiazole cyanine dyes (Henary, M.; Paranjpe, S.; Owens, E. A. Synthesis and application of benzothiazole containing cyanine dyes. Heterocycl. Commun. 2013, 19, 1–11), we will focus in this review on the synthesis and medical applications of alternate compounds that utilize the benzothiazole scaffold as a part of their molecular structure. Benzothiazole derivatives encompass an attractive heterocyclic class that exhibits exciting medicinal properties. The applicability of these heterocyclic structures includes positron emission tomography probes for monitoring Alzheimer’s disease progression; furthermore, these compounds exhibit antimicrobial, anti-inflammatory, anticancer, antidiabetic and anti-HIV activity. Benzothiazole-containing heterocyclic structures are prominent throughout the literature and it is very important to acknowledge their efficacy and applicability. Herein, we review the recent developments covering the past few years concerning the advancements in synthetic methodology for the preparation of medicinally relevant benzothiazole-containing heterocyclic structures.

Synthesis of a series of 8-phenylthiazolo[4,5- e ][1,2,4]triazolo[1,5- c ]pyrimidin-5(4 H )-one and 5-piperazino-8-phenylthiazolo[4,5- e ][1,2,4]triazolo[1,5- c ]pyrmidine compounds with promising biological activity is described.

A new series of 10-phenyl-7,9-dihydro-3 H -furo[3,4- b ]pyrazolo[4,3- f ]quinolin-9-one derivatives has been synthesized through an efficient multicomponent reaction of tetronic acid, 5-aminoindazole and various aromatic aldehydes catalyzed by copper(II) triflate under ultrasonic irradiation.

Synthesis of 3-( t -butylimino or cyclohexylimino)-2-aryl-2,3-dihydropyrrolo[2,1- a ]isoquinoline-1,1(10b H )-dicarbonitriles was developed through a one-pot four- component high-yield reaction of malononitrile, an aldehyde, isoquinoline and t -butylisocyanide or cyclohexylisocyanide. The simple, mild, and efficient reaction is conducted in dichloromethane at room temperature.

An efficient procedure for the oxidative cyclization of N -acylhydrazones was developed utilizing tert -butyl hypoiodite ( t -BuOI), which is generated in situ from t -BuOCl and NaI. A variety of 2,5-disubstituted 1,3,4-oxadiazoles were synthesized in high yields within short reaction time. The method is also suitable for cyclization of N -acylhydrazones derived from heterocyclic aldehydes and aliphatic aldehydes. Mild reaction conditions and simple workup operations make the procedure a good alternative for the synthesis of 2,5-disubstituted 1,3,4-oxadiazoles.

Readily available 2-(toluene-4-sulfonylamino)ethylamine is a convenient starting material for a two-step synthesis of 1-[2-(toluene-4-sulfonamido)ethyl]thiourea ( 2 ). Heterocyclization of the thiourea moiety in 2 furnished a thiazole derivative 3 which was further functionalized into substituted thiazoles 4–6 . A series of 2-(thiazol-5-yl)-[1,3,4]oxadiazoles 8 , 10 and 2-(thiazol-5-yl)-[1,3,4]thiadiazoles 9 , 11 were obtained.

A series of new benzimidazole derivatives, namely 2-acylbenzimidazoles 2–9 , a dihydroquinoxaline 10 , a benzoxazine 11 , quinolines 13–15 and fused 1,2,4-triazines 17–24 were synthesized. Structure elucidation of the compounds was conducted using IR, 1 H NMR, 13 C NMR, mass spectral data and elemental analysis. These products were evaluated for in vitro antitumor activity against MCF7 cell line (human breast cancer). Compounds 13–15 and 24 manifested significant antitumor activity.

A novel approach to isoflavone glycoconjugates, designed as less biodegradable congeners of natural glycosides, is presented on example of daidzein linkage to a C-glycosidic synthon derived from l -rhamnose. 1,3-Dipolar cycloaddition was employed for chemical ligation of daidzein 7- O -propargyl ester and alkyl azide containing 2,3-unsaturated pyranoside moiety. The obtained constructs with opposite anomeric configuration both exhibited a considerable increase in cytotoxic activity against the HTC 116 cell line, in comparison to the parent isoflavone.

The ionic liquid [H 3 N + CH 2 CH 2 OH][CH 3 COO - ] (HEAA) catalyzes a three-component, one-pot condensation of malononitrile/ethyl cyanoacetate, 1,3-dicarbonyl compound/enol, and quinone or ninhydrin in water to afford a spiropyran derivative. This method has advantages of mild reaction conditions, short reaction time, and environmental friendliness.