Design and synthesis of new series of 3‐cyanopyridine and pyrazolopyridine derivatives

Keshk, Reda Mohammed

doi:10.1002/jhet.4058

Cited by 10 publications

(8 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Reacting compounds 1a or 1b with acetylacetone in the presence of conc. HCl afforded 2,4,8,10-tetramethylpyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine 2 in high yield percent and shorter reaction time compared to the previously reported procedures [ 18 , 20 ]. The formation of compound 2 from 1b instead of 3-acetyl-4,8,10-trimethylpyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine attributed to the hydrolysis of amide linkage of 1b by hydrochloric acid before cyclization to the final product.…”

Section: Resultsmentioning

confidence: 89%

Selective Sensing of Darolutamide and Thalidomide in Pharmaceutical Preparations and in Spiked Biofluids

2022

Self Cite

View full text Add to dashboard Cite

Selective spectrofluorometric sensing is introduced for the analysis of non-steroidal anti-androgens, darolutamide, and thalidomide in pharmaceutical preparations and biofluids. An organic fluorophore, 2,4,8,10-tetramethylpyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine 2 was synthesized in our laboratories by new simple methods to act as a fluorescent reagent for the analysis of the studied drugs. Elemental and spectral analyses were performed to approve the fluorophore structure. The fluorophore possesses a fluorescence at λem 422 nm when excited at 328 nm. The interaction between the studied drugs and the fluorophore was found to be quenching. The quenching mechanisms were studied and interpreted through the Stern–Volmer relationship. Moreover, the Stern–Volmer constants were calculated for the quenching interactions of both drugs. The introduced method was validated for the estimation of darolutamide and thalidomide in dosage forms, plasma, and urine, offering good percentage recoveries.

show abstract

Section: Resultsmentioning

confidence: 89%

Selective Sensing of Darolutamide and Thalidomide in Pharmaceutical Preparations and in Spiked Biofluids

2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Keshk 39 Yield: 70%, mp 196 °C (Lit. 39 General Procedure for the Preparation of Compounds (3−6 and 8,9). To a solution of oxadiazole-thione 2 (1.0 mmol) in acetone (20 mL), potassium carbonate (1.2 mmol) was added and stirred for 1 h; then the appropriate alkyl or galactosyl bromide (1.1 mmol) was added.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Design and Synthesis of Novel Pyridine-Based Compounds as Potential PIM-1 Kinase Inhibitors, Apoptosis, and Autophagy Inducers Targeting MCF-7 Cell Lines: In Vitro and In Vivo Studies

Shaban,

Eltamany,

Boraei

et al. 2023

ACS Omega

View full text Add to dashboard Cite

2-((3-Cyano-4,6-dimethylpyridin-2-yl)oxy)acetohydrazide 1 was used as the precursor for the synthesis of 5-thioxo-1,3,4-oxadiazol-2-yl)methoxy)nicotinonitrile 2 . The latter was alkylated with different alkylating agents to produce the S-alkylated products 3–6 . Galactosylation of 5-thioxo-1,3,4-oxadiazol-2-yl)methoxy)nicotinonitrile 2 produces a mixture of S- and N-galactosides 8 and 9 . The hydrazide 1 is converted to azide 10 , coupled with glycine methyl ester hydrochloride and a set of amines to produce the target coupled amides 11–15 . New compounds were assigned using NMR and elemental analysis. Compound 12 had potent cytotoxicity with IC 50 values of 0.5 and 5.27 μM against MCF-7 and HepG2 cell lines compared with doxorubicin, which displayed the following IC 50 : 2.14 and 2.48 μM for the mentioned cell lines, respectively. Regarding the molecular target, compound 12 exhibited potent PIM-1 inhibition activity with 97.5% with an IC 50 value of 14.3 nM compared to Staurosporine (96.8%, IC 50 = 16.7 nM). Moreover, compound 12 significantly activated apoptotic cell death in MCF-7 cells, increasing the cell population by total apoptosis by 33.43% (23.18% for early apoptosis and 10.25% for late apoptosis) compared to the untreated control group (0.64%), and arresting the cell cycle at S-phase by 36.02% compared to control 29.12%. Besides, compound 12 caused tumor inhibition by 42.1% in solid tumors in the SEC-bearing mice. Results disclosed that compound 12 significantly impeded cell migration and cell proliferation by interfering with PIM-1 enzymatic activity via considerable apoptosis-induction, which made it an attractive lead compound for the development of chemotherapeutics to treat breast cancer.

show abstract

“…Reaction of compound 2 with phosphorous oxychloride for 3 h afforded pyridopyrazolopyrimidine 3 in low yield percent (41%). On trying to synthesized compound 3 in high yield percent than above and reported procedures [30,38], pyrazolopyridine 1 was heated with ethyl acetoacetate under reflux in the presence of (ethanol, ethanol/conc. HCl and CH 2 Cl 2 /POCl 3 ).…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis, and characterization of novel pyrazolopyridine and pyridopyrazolopyrimidine derivatives

Keshk

2022

Journal of Heterocyclic Chem

Self Cite

View full text Add to dashboard Cite

Novel derivatives of pyrazolopyridine and pyridopyrazolopyrimidine were synthesized as these nitrogen heterocyclic compounds have biological and pharmaceutical application. Reaction of 4,6‐dimethyl‐1H‐pyrazolo[3,4‐b]pyridin‐3‐amine 1 with ethyl acetoacetate afforded 3‐(4,6‐dimethyl‐2H‐pyrazolo[3,4‐b]pyridin‐3‐ylamino)‐but‐2‐enoic acid ethyl ester 2 and 2,8,10‐Trimethylpyrido[2′,3′:3,4]pyrazolo[1,5‐a]pyrimidin‐4‐ol 3. The reaction product depends on the reaction time and catalyst applied. The reaction of ester 2 with POCl3 afforded pyridopyrazolopyrimidine 3 which reacted with ethyl bromoacetate to afford (2,8,10‐trimethylpyrido[2′,3′:3,4]pyrazolo[1,5‐a]pyrimidin‐4‐yloxy)acetic acid ethyl ester 4, while the reaction of compound 3 with POCl3 afforded 4‐chloro‐derivative 5, which reacted with hydrazine and a series of amines (primary and secondary) to yield 6 and 7a–n, respectively. 4‐Hydrazino pyridopyrazolopyrimidine 6 reacted with aromatic aldehydes, aromatic ketones, acetylacetone, and ethyl acetoacetate to afford condensation products 8–11. The reaction of ester 2 with ethyl chloroacetate afforded diester 12, which reacted with ethanolamine and hydrazine to afford 13, 14. Pyrazolopyridine 14 reacted with excess acetylacetone to yield pentenone derivative 15. The newly synthesized compound structure was confirmed by elemental analysis and spectral data (IR, NMR and mass spectra).

show abstract

Design and synthesis of new series of 3‐cyanopyridine and pyrazolopyridine derivatives

Cited by 10 publications

References 42 publications

Selective Sensing of Darolutamide and Thalidomide in Pharmaceutical Preparations and in Spiked Biofluids

Selective Sensing of Darolutamide and Thalidomide in Pharmaceutical Preparations and in Spiked Biofluids

Design and Synthesis of Novel Pyridine-Based Compounds as Potential PIM-1 Kinase Inhibitors, Apoptosis, and Autophagy Inducers Targeting MCF-7 Cell Lines: In Vitro and In Vivo Studies

Design, synthesis, and characterization of novel pyrazolopyridine and pyridopyrazolopyrimidine derivatives

Contact Info

Product

Resources

About