Pyridine 5a Research Articles

New thiazole derivatives linked to pyridine, fused pyridine, pyrimidine and thiazolopyrimidine scaffolds with potential dual anticancer and antimicrobial activities: Design, synthesis and docking simulation

The present study involved the design and synthesis of a novel series of thiazole derivatives 3, 5, 7, 8, 10–13 having various heterocyclic scaffolds, including pyrazole, pyridine, and/or pyrimidine. Upon screening of their antiproliferative efficacy, pyrazolo[3,4-b]pyridine 5a,b and pyrimidine 10a,b, afforded excellent activity against cancerous HepG-2 and MCF-7 cell lines with safety borders against normal human diploid cell line WI-38 comparing with doxorubicin and erlotinib. Then, their impact upon the apoptotic indicators; caspase-3, Bax and Bcl-2 was assessed. Regarding to antimicrobial activities, all screened Gram-positive and Gram-negative bacteria and fungal strains except Candida albicans, were effectively inhibited by the thiazole moiety bearing pyrazolo[3,4-b]pyridine 5a,b and pyrimidine 10a,b. Additionally, thiazole-pyrazolo[3,4-b]pyridine 5b exhibited remarkable and superior inhibitory properties against EGFR and E. coli DNA gyrase (IC50 = 0.3‏5 ± 0.‏25 and ‏‏2‏‏‏.55‏ ± 0.03 µM, respectively) in comparison with references erlotinib and novobiocin (IC50 = 0.27 ± 0.02 and 3.78 ± 0.02 µM, respectively). In order to provide improved optimization and rationalization of effective novel anticancer and antimicrobial leads, in silico ADMET and docking investigations were ultimately constructed.

Construction and Functionalization of Highly Strained N -Doped Zigzag Hydrocarbon Belts

Construction and Functionalization of Highly Strained <i>N</i> -Doped Zigzag Hydrocarbon Belts

Synthesis of Dihydroisoquinoline and Dihydropyridine Derivatives via Asymmetric Dearomative Three-Component Reaction

Synthesis of Dihydroisoquinoline and Dihydropyridine Derivatives via Asymmetric Dearomative Three-Component Reaction

Novel 2-methyl-6-arylpyridines carrying active pharmacophore 4,5-dihydro 2-pyrazolines: synthesis, antidepressant, and anti-tuberculosis evaluation

As part of the effort to develop new hybrid molecules for the treatment of depression and tuberculosis, a new series of novel 6-aryl-2-methyl-3-(5-aryl-4,5-dihydro-1H-pyrazol-3yl)pyridines 5a–l were synthesized. These compounds were screened for in vivo antidepressant activity following both modified forced swimming test (FST) and tail suspension test (TST) at a test dose of 100 mg kg−1. Preliminary antidepressant screening of 5a–l revealed that compound 5b showed significant decrease in the immobility time when compared to normal control group in both FST and TST and was found to be more active than the standard imipramine (10 mg kg−1, ip). Compounds 5f, 5h, 5j, and 5l displayed moderate to good antidepressant activity. All synthesized compounds were also screened for their in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain. Compounds 5a, 5c, and 5i showed highest anti-tubercular activity with MIC value 12.5 µg mL−1 comparable to the standard drugs.

Design, Synthesis, and Cytotoxicity Evaluation of 3‐(5‐(3‐(aryl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)pyridine and 5‐(3‐(aryl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐3‐(pyridin‐3‐yl)‐4,5‐dihydropyrazole‐1‐carbaldehyde Derivatives as Potential Anticancer Agents

In an attempt to find bio‐active small molecules, a series of novel 3‐(5‐(3‐(aryl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1‐phenyl‐4,5‐dihydro‐1H‐pyrazol‐3‐yl)pyridine 5a–i and 5‐(3‐(aryl)‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐3‐(pyridin‐3‐yl)‐4,5‐dihydropyrazole‐1‐carbaldehyde 6a–i were designed, synthesized, and evaluated for their in vitro cytotoxic activity against a panel of human cancer cell lines namely; HeLa (human cervix), NCI‐H460 (human lung), PC‐3 (human prostate), and NIH‐3T3 (mouse embryo fibroblasts) normal cell line. Most of these compounds exhibited moderate to good cytotoxic activity against the tested cancer cell lines and weak toxicity against normal cell line. Analogues 5b, 5f, 5g, 6b, and 6g showed significant cytotoxicity as compared to standard drug etoposide. Among all the synthesized compounds, compound 6g displayed superior cytotoxicity with an IC50 value of 7.98 ± 1.08 μM for Hela cancer cell line.

N-(Propargyl)diazenecarboxamides for ‘click’ conjugation and their 1,3-dipolar cycloadditions with azidoalkylamines in the presence of Cu(II)

Propargyl functionalized diazenes 1 were prepared by two different approaches and were examined as alkyne click components in copper-catalyzed azide–alkyne cycloadditions (CuAAC) with 2-(azidomethyl)pyridine 5a and four α-azido-ω-aminoalkanes C2–C5 ( 5b– e). Whereas the reactions with azidoalkylamines 5b– e reached completion with copper(II) sulfate without the need of reducing agent typically in no more than few minutes, 2-(azidomethyl)pyridine 5a required the addition of metallic copper and much longer reaction times (2–24 h). This difference in the reactivity was studied and addressed in terms of base effect and proximity effect to CuAAC.

Studies of Thiazolopyridines. Part 6. Synthesis and Antimicrobial Evaluation of Some Novel Thiazolo[3,2‐a]pyridine and Thiazolo[2′,3′:6,1]pyrido[2,3‐d]pyrimidine Derivatives.

Condensation of thiazolinone 1 with aromatic aldehydes yielded the corresponding methylidene derivatives 2a–f. Cyclization of compounds 2a–f with arylidenemalononitrile 3 (1:1 molar ratio) in ethanol in the presence of piperidine furnished the novel thiazolo[3,2-a]pyridines 5a–v, via Michael adduct 4. Compounds 5p, r were cyclized with malononitrile in the presence of piperidine to yield thiazolo[3,2-a][1,8]naphthryidines 7a, b. Thiazolo-[2′,3′:1,6]pyrido[2,3-d]pyrimidine 9a–cwere obtained by cyclization of compounds 5c, p, r with formic acid. The structure of the synthesized compounds was established by analytical and spectral data. Also, some of the synthesized compounds were screened for antimicrobial activity in vitro.

Studies of Thiazolopyridines, Part 6: Synthesis and Antimicrobial Evaluation of Some Novel Thiazolo[3,2-a] Pyridine and Thiazolo[2′,3′:6,1]-pyrido[2,3-d]pyrimidine Derivatives

Condensation of thiazolinone 1 with aromatic aldehydes yielded the corresponding methylidene derivatives 2a–f. Cyclization of compounds 2a–f with arylidenemalononitrile 3 (1:1 molar ratio) in ethanol in the presence of piperidine furnished the novel thiazolo[3,2-a]pyridines 5a–v, via Michael adduct 4. Compounds 5p, r were cyclized with malononitrile in the presence of piperidine to yield thiazolo[3,2-a][1,8]naphthryidines 7a, b. Thiazolo-[2′,3′:1,6]pyrido[2,3-d]pyrimidine 9a–cwere obtained by cyclization of compounds 5c, p, r with formic acid. The structure of the synthesized compounds was established by analytical and spectral data. Also, some of the synthesized compounds were screened for antimicrobial activity in vitro.

Studies on the Synthesis of New 3‐(3,5‐Diamino‐1‐substituted‐pyrazol‐4‐yl)azo‐thieno[2,3‐b]pyridines and 3‐(2‐Amino‐5,7‐disubstituted‐pyrazolo[1,5‐a]pyrimidine‐3‐yl)azothieno[2,3‐b]pyridines

AbstractCoupling the diazonium salt of 3‐amino‐2‐cyano‐4,6‐dimethylthieno[2,3‐b]pyridine 1 with malononitrile 2 gave 2‐cyano‐3‐(hydrazonomalononitrile)‐4,6‐dimethylthieno[2,3‐b]pyridine 3 which then reacted with hydrazine compounds 4a‐4h to yield corresponding 2‐cyano‐3‐(3,5‐diamino‐1‐substituted‐pyrazol‐4‐yl)azo‐4,6‐dimethylthieno[2,3‐b]pyridines 5a‐5h. The 2‐cyano‐3‐(2‐amino‐5,7‐disubstituted‐pyrazolo‐[1,5‐a]pyrimidine‐3‐yl)azo‐4,6‐dimethylthieno[2,3‐b]pyridines 7a‐7f were obtained in good yield by the cyclocondensation reaction of 2‐cyano‐3‐(3,5‐diamino‐pyrazol‐4‐yl)azo‐4,6‐dimethylthieno[2,3‐b]pyridine 5a with the appropriate 1,3‐diketones 6a‐6f under acidic condition.

Novel solid‐state synthesis of dimeric 4‐aryl‐1,4‐dihydropyridines

AbstractOn irradiation in the solid state the 4‐aryl‐1,4‐dihydroypridines 1 undergo [2+2] cycloadditon to centrosymmetric head‐to‐tail dimers 3 and 4a. The almost exclusive formation of the cage dimers 3 via the C2‐symmetric syn‐dimers 2 takes place in nearly quantitative yields, in contrast with the cycloaddition reaction of the anti‐dimer 4a, which is accompanied by photooxidation to pyridine 5a.

REACTIONS WITH PYRIDINETHIONE DERIVATIVES: SYNTHESIS AND CHARACTERIZATION OF THIENYL[2,3-b]PYRIDINE, PYRIDO[2′,3′:4,5] THIENO[2,3-b]PYRIDAZINE, PYRIDO[2′,3′:4,5] THIENO[2,3-b]-PYRIMIDINONE, PYRAZOLINO [3′,4′:4,5] THIENO[2,3-b]PYRIDINE AND AMINOPYRAZOLO[3,4-b]PYRIDINE DERIVATIVES

Thieno[2,3-b]pyridines 5a,b, 2-S-methylacetyl pyridine derivative 7 , 2-S-methyldiaetyl pyridine derivative 7b, 2-S-methylethoxycarbonyl pyridine derivative 12a, 2-S-methylacetylethoxycarbonyl pyridine derivative 12 and 2-S-methyl pyridine derivative 28 , had been obtained via the reaction of pyridinethione 3 with phenacyl bromide derivatives, chloroacetone, α-chloroacetylacetone, chloroethylacetone, α-chloroethylacetoacetate and methyl iodide respectively. Several cyclization reactions were performed with 10% KOH, nitrous acid, hydrazine hydrate, formic acid, acetic anhydride and acetic acid to give an additional ring on the previously obtained new ring system.

Sterically Crowded Heterocycles. III. A General Approach to Imidazo[1,2-a]pyridines by Ferricyanide Oxidation of Quaternary Pyridinium Salts

Substituted 1-(pyridin-2-yl)-2,4,6-triphenylpyridinium perchlorates 1b-1e were converted with potassium ferricyanide and potassium hydroxide to sterically crowded 2-phenyl-3-[(Z)-1,3-diphenyl-3-oxopropenyl]imidazo[1,2-a]pyridines 2b-2e accompanied by minor isomeric 2-benzoyl-3,5-diphenyl-1-(pyridin-2-yl)pyrroles 3c-3e. 4-Phenyl-2,6-di(4-substituted phenyl)-1-(pyridin-2-yl)pyridinium salts 4a, 4b gave exclusively corresponding imidazo[1,2-a]pyridines 5a, 5b while the ferricyanide oxidation of 1-(5-iodo- and 5-cyanopyridin-2-yl)-2,4,6-triphenylpyridinium perchlorates 6a, 6b led to mixtures of major imidazo[1,2-a]pyridines 7a-7c and minor pyrroles 8a-8c. Some mechanistic aspects of the oxidation procedure are discussed in connection with a resistance of 2,6-diphenyl-1,3,5-trimethylpyridinium perchlorate (9c) towards the oxidizing agents.

The synthesis and the structure-activity relationships of some substituted benzoxazoles, oxazolo(4,5- b)pyridines, benzothiazoles and benzimidazoles as antimicrobial agents

The synthesis of a new series of 2,5-disubstituted benzoxazoles 4a–f, 2-substituted oxazolo(4,5- b)pyridines 5a, b, benzothiazoles 6a, b and benzimidazoles 7a, b is described in order to determine their antimicrobial activities and feasible structure-activity relationships (SAR). The synthesized compounds were tested in vitro against 3 Gram-positive, 3 Gram-negative, and a fungus Candida albicans, 4b, 4e and 4f were found to be more active than the others against Klebsiella pneumoniae at a MIC value of 12.5 μg/ml. All the derivatives 4–7 exhibited significant antimycotic activity against C albicans. The antibacterial and antimycotic activities of 4–7 are also compared with several standard drugs.