Facile Synthesis and In‐Vitro Antitumor Activity of Some Pyrazolo[3,4‐b]pyridines and Pyrazolo[1,5‐a]pyrimidines Linked to a Thiazolo[3,2‐a]benzimidazole Moiety

Abstract

The key precursor E-3-(N,N-dimethylamino)-1-(3-methylthiazolo[3,2-a]benzimidazol-2-yl)prop-2-en-1-one 4 was synthesized in good yield using Gold's reagent. The reaction of enaminone 4 with 5-amino-3-aryl-1-phenylpyrazoles 5a, b in refluxing acetic acid in the presence of sulphuric acid, yielded pyrazolo[3,4-b]pyridines 7a, b. Similarly, pyrazolo[1,5-a]pyrimidines 10a, b and 14a-f were prepared by reaction of enaminone 4 with 5-amino-1H-pyrazoles 8a, b and 12a-f, respectively. The structure of pyrazolo[1,5-a]pyrimidine 10b was determined by X-ray diffraction. The synthesized compounds were tested for their in-vitro antitumor activity against the colon cancer cell line CaCo-2; their cytotoxicity against the normal fibroblast cell line BHK was explored as well. Some of the tested compounds exhibited cell growth inhibitory activity. The significant antitumor activity of compound 14f against the CaCo-2 cell line (IC(50 )= 0.5 microg/mL) was coupled with a lower toxicity against BHK (IC(50 )= 2.3 microg/mL).

Multistage Fragmentation of Ion Trap Mass Spectrometry System and Pseudo-MS3of Triple Quadrupole Mass Spectrometry Characterize Certain (E)-3-(Dimethylamino)-1-arylprop-2-en-1-ones: A Comparative Study

“…Several methods for the preparation of enaminones have been reported [24]. Enaminones 4a–j were efficiently prepared by the reaction of ketone 1a–j with dimethylformamide-dimethylacetal (DMF - DMA) ( 2 ) or with [3-(dimethylamino)-2-azaprop-2-en-1-ylidene] dimethylammonium chloride (Gold's reagent) (Scheme 1) ( 3 ).…”

“…Thus, there is necessity to improve the known analyses methods for this class of compounds or develop new methods. In continuation for our previous work [19–24] in the chemistry of the title compounds, certain enaminones 4a–j were synthesized and used as model compounds for this current study.…”

Thiazolo[3,2-a]benzimidazoles: Synthetic Strategies, Chemical Transformations and Biological Activities

“…1-(3-Methylthiazolo[3,2- a ]benzimidazol-2-yl)ethanone ( 10b ) was treated with dimethylformamide-dimethylacetal (DMF-DMA), in dry xylene, at reflux temperature, it afforded E -3-( N , N -dimethylamino)-1-(3-methylthiazolo[3,2- a ]benzimidazol-2-yl)prop-2-en-1-one ( 93 ) [ 70 ] ( Scheme 32 ). Recently, Abdel-Aziz et al reported an alternative synthesis of compound 93 using [3-(dimethyl-amino)-2-azaprop-2-en-1-ylidene]dimethylammonium chloride (Gold’s reagent) [ 71 ] where Gold's reagent reacted with ketone 10b in sodium methoxide to produce the enaminone 93 ( Scheme 32 ). The reaction of compound 93 with aminopyrazoles 94 in refluxing pyridine [ 70 ] or in acetic acid presence of H 2 SO 4 [ 71 ] afforded pyrazolo[1,5- a ]pyrimidines 95 .…”

“…Recently, Abdel-Aziz et al reported an alternative synthesis of compound 93 using [3-(dimethyl-amino)-2-azaprop-2-en-1-ylidene]dimethylammonium chloride (Gold’s reagent) [ 71 ] where Gold's reagent reacted with ketone 10b in sodium methoxide to produce the enaminone 93 ( Scheme 32 ). The reaction of compound 93 with aminopyrazoles 94 in refluxing pyridine [ 70 ] or in acetic acid presence of H 2 SO 4 [ 71 ] afforded pyrazolo[1,5- a ]pyrimidines 95 .…”

An Alternative Regioselective Approach for the Synthesis of Highly Functionalized Derivatives of Pyrazolo[5,1‐b]purine Scaffold

“…Because of the importance of pyrazolo[1,5‐ a ]pyrimidine scaffold, various methods for its synthesis have been developed. Most of them involve the condensation reaction between aminopyrazoles and 1,3‐ bis ‐electrophilic reagents, such as 1,2‐allenic ketones , enaminones , enaminonitriles , β‐ketonitriles , 1,3‐dicarbonyl compounds , and α,β‐unsaturated carbonyl compounds .…”