Pyridines 4a Research Articles

High pressure assisted synthetic approach for novel 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline derivatives and their assessment as anticancer agents

A novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline systems has been developed with a new synthetic platform. This process includes ammonium acetate-mediated cyclocondensation reactions of 3-oxo-2-arylhydrazonopropanals with benzosuberone and tetralone precursors, respectively, using the high-pressure Q-tube reactor, which has been found to be superior to both conventional heating and microwave irradiation. The novel protocol benefits from its high atom efficiency, economy, ease of workup, broad substrate scope and is also applicable to gram-scale synthesis. To identify and confirm the newly synthesized targeted compounds, the X-ray single-crystal as well as all possible spectroscopic methods were utilized. The cytotoxicity of the newly synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j and 5,6-dihydrobenzo-[h]quinolines derivatives 6a–e were preliminary examined toward three cell lines of human cancer; lung cancer (A549), breast cancer (MCF-7) and colon cancer (HCT-116), by applying the MTT colorimetric assay. The achieved results reflected the promising profile of the prepared compounds in this study against cancer cells and have shown that members from the synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j exhibited promising cytotoxicity’s against MCF-7, and A549 cancer cells respectively, while the HCT-116 (colon) cancer cells were inhibited by certain examples of 5,6-dihydrobenzo[h]quinoline derivatives 6c,d. These promising results could serve as a good primary base for further research into the design of anticancer drugs.

New furochromone derivatives as promising in‐vitro anti‐proliferative agents toward HepG‐2 and MCF‐7 cell lines with molecular docking studies

AbstractBased on the considerable features of the multicomponent reactions (MCRs) in the field of organic and medicinal chemistry, the present work was designed to synthesize a new series of imidazole, pyridine, and pyrimidine derivatives using MCRs to obtain new anti‐proliferative agent beside exploration of their interaction mechanism by molecular docking technique. MCRs of furochromone carbaldehyde 1, benzoin, and ammonium acetate afforded the corresponding 2,4,5‐trisubstituted imidazole 2. However, MCRs of 1 with benzoin, amine derivatives, and ammonium acetate yielded the corresponding 1,2,4,5‐tetrasubstituted imidazole 3a,b. In addition, pyridine 4a,b‐5a,b and pyrimidine derivatives 6a,d were synthesized via condensation of 1 with different carbonyl compounds and ammonium acetate or benzyl urea, respectively. The in‐vitro anti‐Proliferative activities of the new furochromone derivatives were screened toward MCF‐7 and HepG‐2 cancer cell lines as well as the normal cell line (human normal melanocyte, HFB4) in comparison to the known anticancer drugs: 5‐fluorouracil and doxorubicin using MTT assay. Compounds 5a and 5b revealed effective anti‐proliferative activity against MCF‐7 cell lines with IC 50 18 and 22 μg/mL, respectively, compared to 5‐fluorouracil (IC 50 of 13 μg/mL). However, compounds 6a‐d exhibited potent activity against HepG‐2 cancer cell lines of IC 50 ranging from 18 to 20 μg/mL compared to doxorubicin (IC 50 of 14 μg/mL). Moreover, the binding mode of the most active furochromones 5a,b and 6a‐d inside the active site of the epidermal growth factor receptor (EGFR) kinase enzyme (PDB ID: 5CAV) were studied using molecular docking technique. Compounds 6b,c showed excellent docking results compared to the known EGFR inhibitors (4ZQ).

Molecular modeling and cyclization reactions of 2-(4-oxothiazolidine-2-ylidene) acetonitrile

Diazotization of 2-(4-oxothiazolidine-2-ylidene) acetonitrile 1 with aryl diazonium chloride derivatives afforded 4-thiazolidinones 2a, b, whereas 3a, b derivatives produced through reaction of arylcarbonohydrazonoyl dicyanide with thioglycolic acid. Cyclization of 2a with aromatic aldehydes and malononitrile gave the expected substituted thiazolo [3,2-a] pyridines 4a, b. The reaction of 1 with anthraldehyde (1:1 molar ratio) gave the expected 4,5-dihydro-4-oxothiazole derivatives 5 which condensed with other mole p-chlorobenzaldehyde and gave the corresponding bisarylidine derivative 6. Thiazolo [3,2-a] pyridine enaminonitrile derivative 7 produced through addition of malononitrile to bisarylidine 6. Also, compound 7 reacted with other mole of malononitrile and furnished thiazolo [3,2-a] pyridine 12, furthermore, compound 7 refluxed with phenyl hydrazine, thiourea, and formic acid, to form the corresponding thiazolo [3,2-a] pyridines 13, 15 and 17, respectively. Also, compound 1 reacted with phNCS in presence of KOH and afforded 19. The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. Also, valuable information is obtained from calculation of the molecular parameters including electronegativity, net dipole moment of the compounds, total energy, electronic energy, binding energy, electrophilicity index, HOMO and LUMO energy.

An Efficient Microwave‐Assisted Synthesis and Antimicrobial Activity of Novel 2‐Amino 3‐Cyano Pyridine Derivatives using Two Reusable Solid Acids as Catalysts

Two solid acids, Fe3+ K‐10 montmorillonite clay and HY‐zeolite, have been employed efficiently for synthesis of 2‐amino 3‐cyano pyridines 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j, 4k, 4l, 4m, 4n, 4o, 4p, 4q, 4r, 4s, 4t, 4u, 4v, 4w, 4x by multicomponent reaction of 3‐acetyl 4‐hydroxy coumarin 1a, 1b, 1c, 1,3‐diphenyl‐1H‐pyrazole‐4‐carbaldehyde 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, malononitrile 3, and ammonium acetate. Both the catalysts are recoverable and recyclable. The main significant of this procedure is short reaction time, high yields, easy workup procedure, and being environmentally friendly. The structures of all the compounds have been well characterized by IR, 1H NMR, 13C NMR, and mass spectral data. All the synthesized compounds were screened for their antimicrobial and antifungal activities.

Synthesis of Certain 3‐Aminopyrazolo[5,4‐b]pyridine and 3,4‐Substituted Pyrido[2′,3′ :3,4]pyrazolo[5,1‐c][1,2,4]triazine Derivatives

Abstract2‐Thioxo‐1,2‐dihydropyridine derivatives 2a, 2b were reacted with methyl iodide to give 2‐methylthiopyridines 3a, 3b, which were reacted with hydrazine hydrate to produce 3‐aminopyrazolo[5,4‐b]pyridines 4a, 4b. Compounds 4a, 4b were diazotized to afford the corresponding diazonium salts 5a, 5b, which were reacted with some active methylene compounds 6a–6h to give the corresponding pyrido[2′,3′:3,4]pyrazole[5,1‐c][1,2,4]triazines 7–14.

Synthesis of Functionalized Pyrano[3,2‐c]pyridines and Their Transformations to 4‐Hydroxy‐3[(1E)‐N‐hydroxyalkanimidoyl]pyridones

Reaction of 4‐hydroxy‐6‐methyl‐2(1H)‐pyridones 1a and 4‐hydroxy‐1,6‐dimethyl‐2(1H)‐pyridones 1b with diethyl malonates 2a–e leads to the formation of pyrano[3,2‐c]pyridines 4a–j. Degradation of 4a–i affords the corresponding ketones 6a–i. Condensation of ketones 6a–i with hydroxyl amine or phenyl hydrazine hydrochloride is described.

Pyridine-2(1H)-thione in Heterocyclic Synthesis: Synthesis of Some New Nicotinic Acid Ester, Thieno[2, 3-b]pyridine, Pyrido[3′, 2′: 4, 5]thieno [3, 2-d]pyrimidine, and Thiazolylpyrazolo[3, 4-b]pyridine Derivatives

Nicotinic acid esters 3a–c were prepared by the reaction of pyridine-2(1H)-thione derivative 1 with α-halo-reagents 2a–c. Compounds 3a–c underwent cyclization to the corresponding thieno[2, 3-b]pyridines 4a–c via boiling in ethanol/piperidine solution. Compounds 4a–c condensed with dimethylformamide-dimethylacetal (DMF-DMA) to afford 3-{[(N,N-dimethylamino)methylene]amino}thieno[2, 3-b]- pyridine derivatives 6a–c. Moreover, compounds 4a–c and 6a–c reacted with different reagents and afforded the pyrido[3′,2′:4, 5]thieno[3, 2-d]pyrimidine derivatives 10a–d, 11a–c, 12a,b, 14a,b, 17, and 19. In addition, pyrazolo[3, 4-b]pyridine derivative 20 (formed via the reaction of 1 with hydrazine hydrate) reacted with ethylisothiocyanate yielded the thiourea derivative 21. Compound 21 reacted with α-halocarbonyl compounds to give the 3-[(3H-thiazol-2-ylidene)amino]-1H-pyrazolo[3, 4-b]pyridine derivatives 23a–c, 25, and 27a,b.

Sequential Amination/Annulation/Aromatization Reaction of Carbonyl Compounds and Propargylamine: A New One‐Pot Approach to Functionalized Pyridines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Sequential amination/annulation/aromatization reaction of carbonyl compounds and propargylamine: a new one-pot approach to functionalized pyridines.

A general one-pot synthesis of pyridines 4a-t from the reaction of dialkyl acyclic/cyclic ketones 1a-i, methyl, aryl/heteroaryl ketones 1m-r, and aldehydes bearing alpha-hydrogens 1s,t with propargylamine 2 is described. Gold and copper salts are efficient catalysts for the reaction of ketones with 2. The formation of the pyridines 4 is suggested to proceed through the sequential amination of carbonyl compounds followed by regioselective 6-endo-dig cyclization of the N-propargylenamine (N-propargyldienamine) intermediate 3(5) and aromatization reaction. Whereas the preparation of linear polycyclic pyridine 4i can be carried out by reacting cholestan-3-one 1i with 2, the angular polycyclic pyridine 4j has been obtained starting from cholest-5-en-3-one 1j. Selectivity of the reaction of polycyclic dicarbonyls 1k,l with 2 has also been investigated.

A new method for generation of 4- and 6-aryl thieno[2,3-c]furans, and 3-aryl furo[3,4-b]pyridine

6-Aryl thieno[2,3-c]furans 2a–c, 4-(3,4-dimethoxyphenyl)thieno[2,3-c]furan 3a, and 3-(3,4-dimethoxyphenyl)furo[3,4-b]pyridine 4a, which were intercepted in situ by dimethyl acetylenedicarboxylate to give the corresponding Diels–Alder adducts in good yields, were generated under acidic conditions from 2-(α-acetoxybenzyl)thiophene-3-carbaldehydes 5a–c, 3-(α-acetoxy-3,4-dimethoxybenzyl)thiophene-2-carbaldehyde 10a and 2-(α-acetoxy-3,4-dimethoxybenzyl)pyridine-3-carbaldehyde 12a, respectively.