3-Aryl-as-triazines as potential antiinflammatory agents

(Benzo)isoquinoline derivatives are of significant interest in different areas of basic and applied organic chemistry. Of special promise are their biological [1][2][3], photophysical, and coordination [4][5][6][7][8] properties. Their use as chiral catalysts [9,10] is also of interest.The most frequently used methods for preparing (benzo)isoquinoline systems are cross-coupling reactions [11,12], which demand the use of special catalysts. We propose a method for preparing (benzo)isoquinoline derivatives based on an aza Diels-Alder reaction with 1,2,4-triazines as dienes and the aryne intermediates acting as dienophiles.The methodology for preparing diverse pyridine derivatives via reaction of the corresponding 1,2,4-triazines has long been known [13][14][15]. However, there are only a few examples of using aryne intermediates in similar reactions. The range of dienophiles in these cases is limited to certain dehydrobenzene derivatives, the generation of which used poorly available anthranilic acids [16,17] despite the marked growth in the chemistry of arynes in recent years [18,19].In our work, we propose a highly efficient method for the preparation of (het)aryl-substituted isoquinoline 1a and benzo[h]isoquinoline 1b, which involves the reaction of arynes 2a,b with the substituted 1,2,4-triazines 3a,b in anhydrous toluene for 24-36 h at 140°C under an argon atmosphere. The target compounds 1a,b were obtained in 76% and 80% yield, respectively. The corresponding arynes were generated in situ by the action of potassium tert-butoxide on the chloro-and bromo-substituted arenes 4a,b.The structure of the obtained compounds 1a,b was confirmed from the 1 H and 13 C NMR spectroscopy, mass spectrometry, and by elemental analysis data. The mass spectra of compounds 1a,b showed the presence of a molecular ion peak.The compounds obtained are 2,2'-bipyridine type ligands with an extended conjugated system, and are of interest from the viewpoint of complex formation and as luminescent materials.

show abstract

“…The 5-phenyl-3-(2-pyridyl)-1,2,4-triazine (3a) [20] and 6-phenyl-3-(2-pyridyl)-1,2,4-triazine (3b) [15] were synthesized by the reported methods.…”

Section: T-buokmentioning

confidence: 99%

Preparation of (benzo)isoquinolines using in situ generated aryne intermediates

Kopchuk

Zyryanov

Коvalev

et al. 2013

Chem Heterocycl Comp

View full text Add to dashboard Cite

show abstract

“…1,2,4-Triazines and its derivatives are a well-known class of azaheterocycles for their broad spectrum of biological activities and natural occurrences (Figure ). Taking Lamictal for example, as a member of the sodium channel blocking class of antiepileptic drugs, it has been used in the treatment of epilepsy, bipolar disorder and so on for a long time. Apart from these impressive biological properties, 1,2,4-triazines have been widely used as 2-azadienes in the inverse electron demanded Diels–Alder reactions to build important heterocyclic skeletons .…”

Section: Introductionmentioning

confidence: 99%

Unexpected O–H Insertion of Rhodium-Azavinylcarbenes with N-Acylhydrazones: Divergent Synthesis of 3,6-Disubstituted- and 3,5,6-Trisubstituted-1,2,4-Triazines

et al. 2017

View full text Add to dashboard Cite

A practical and efficient method for divergent synthesis of 3,6-disubstituted- and 3,5,6-trisubstituted-1,2,4-triazines via unexpected rhodium-catalyzed O-H insertion/rearrangement/conditions-controlled intramolecular cyclization and oxidation reaction under mild conditions has been developed. Notably, it is the first example for the synthesis of 1,2,4-triazines with different substituted-patterns via a common intermediate with excellent chemoselectivities by the reaction of N-acylhydrazones as aze-[3C] or [4C] synthons with N-sulfonyl-1,2,3-triazoles as aze-[2C] synthons. Furthermore, this method allows direct access to di(het)aryl ketone frameworks containing 1,2,4-triazine moiety for the first time, serving as a versatile building block for the synthesis of other useful heterocyclic skeletons, such as pyridine or pyridazinone-fused triazine in excellent yields.

show abstract

“…1,2,4-Triazine scaffold has been associated with diversified pharmacological activities, such as antiplatelet 14,25 , anticancer 26 , thromboxane synthetase inhibition 27 , anti-inflammatory 28 and antimalarial 29 . Further, the diaryl system attached to 1,2,4-triazine heterocycle has been reported to be a potent anticytokine, mediating through the inhibition of p38 MAPK signaling pathway 30 .…”

Section: Introductionmentioning

confidence: 99%

Design, green synthesis and pharmacological evaluation of novel 5,6-diaryl-1,2,4-triazines bearing 3-morpholinoethylamine moiety as potential antithrombotic agents

Tamboli

Giridhar

Gandhi

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

The aim of this research work was to investigate a series of novel 5,6-diaryl-1,2,4-triazines (3a-3q) containing 3-morpholinoethylamine side chain, and to address their antiplatelet activity by in vitro, ex vivo and in vivo methods. All compounds were synthesized by environment benign route and their structures were unambiguously confirmed by spectral data. Compounds (3l) and (3m) were confirmed by their single crystal X-ray structures. Out of all the synthesized compounds, 10 were found to be more potent in vitro than aspirin; six of them were found to be prominent in ex vivo assays and one compound (3d) was found to have the most promising antithrombotic profile in vivo. Moreover, compound (3d) demonstrated less ulcerogenicity in rats as compared to aspirin. The selectivity of the most promising compound (3d) for COX-1 and COX-2 enzymes was determined with the help of molecular docking studies and the results were correlated with the biological activity.

show abstract

3-Aryl-as-triazines as potential antiinflammatory agents

Cited by 37 publications

References 3 publications

Preparation of (benzo)isoquinolines using in situ generated aryne intermediates

Preparation of (benzo)isoquinolines using in situ generated aryne intermediates

Unexpected O–H Insertion of Rhodium-Azavinylcarbenes with N-Acylhydrazones: Divergent Synthesis of 3,6-Disubstituted- and 3,5,6-Trisubstituted-1,2,4-Triazines

Design, green synthesis and pharmacological evaluation of novel 5,6-diaryl-1,2,4-triazines bearing 3-morpholinoethylamine moiety as potential antithrombotic agents

Contact Info

Product

Resources

About