Antitumor and antiviral activity of synthetic .alpha.- and .beta.-ribonucleosides of certain substituted pyrimido[5,4-d]pyrimidines: a new synthetic strategy for exocyclic aminonucleosides

Sanghvi, Yogesh S.; Larson, Steven B.; Matsumoto, Steven S.; Nord, L. Dee; Smee, Donald F.; Willis, Randall C.; Avery, Thomas L.; Robins, Roland K.; Revankar, Ganapathi R.

doi:10.1021/jm00123a022

Cited by 70 publications

(20 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pyrimidine derivatives have attracted considerable interest in recent years in diverse biological problems (5,6). Experts use pyrimidine derivatives in many different biological applications, including anti-tumor (7), antiviral (7,8), antioxidant (9), antifungal (10), and hepatoprotective (11) roles. FDA-approved drug Brigatinib (marketed as Alunbrig) is a pyrimidine-based small-molecule used in targeted cancer therapy (12).…”

Section: Introductionmentioning

confidence: 99%

Identifying the Novel Pyrimidine-Based CDK2 Inhibitors as Anticancer Agents Using Text-Mining and Combined Molecular Modeling Approaches

Şahin

Durdağı

2020

Journal of the Turkish Chemical Society Section A: Chemistry

View full text Add to dashboard Cite

The cycline-dependent kinase (CDK) protein is a vital target used in anti-cancer drug designing studies. Many FDA-approved drugs, including anti-cancer drugs, use pyrimidine as a crucial fragment. In the current study, a small molecule database (Specs SC) that text mining studies include more than 210.000 compounds, and we filtered 6668 molecules that carry "pyrimidine" fragments. We then screened these compounds at the binding pocket of CDK-2 target using molecular docking and molecular dynamics (MD) simulations approaches. Besides, we compared the binding free energies of screened compounds with pyrimidine-based FDA-approved anti-cancer drug Abemaciclib which targets CDK. Based on the comparison of docking scores of screened compounds, we used top-7 hits in 100 ns MD simulations. We also applied the same MD simulations protocol (100 ns) to the Abemaciclib-bound CDK-2 complex structure. We then calculated the average Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) energies. Our MM/GBSA results showed that 6 out of 7 compounds have better MM/GBSA scores than FDAapproved compound Abemaciclib. Thus, together with a combination of text mining and integrated molecular modeling approaches, we identified novel pyrimidine-based hits against CDK.

show abstract

Section: Introductionmentioning

confidence: 99%

Identifying the Novel Pyrimidine-Based CDK2 Inhibitors as Anticancer Agents Using Text-Mining and Combined Molecular Modeling Approaches

Şahin

Durdağı

2020

Journal of the Turkish Chemical Society Section A: Chemistry

View full text Add to dashboard Cite

show abstract

“…Among them, pyrimido[4,5‐ d ]pyrimidines are an important class of annulated uracils of biological significance . These compounds have attracted considerable attention in medicinal chemistry due to their significant and diverse biological activities, including antitumor, antioxidant, hepatoprotective, antiviral, and antifungal . Some of their derivatives are also useful as bronchodilators, vasodilators, antiallergic,, antihypertensive and anticancer agents.…”

Section: Introductionmentioning

confidence: 99%

Concise Pyrimido[4,5‐d]pyrimidine Synthesis via Direct Annulation of N‐Uracil Amidines with Benzaldehydes Under Transition Metal Free Conditions

Debnath¹,

Sahu²,

2019

ChemistrySelect

View full text Add to dashboard Cite

A novel and concise route towards the synthesis of pyrimido [4,5-d]pyrimidines via a direct annulation reaction of N-uracil amidines with benzaldehydes under transition metal free conditions has been described. The requisite precursors Nuracil amidines are obtained via S N AE reaction on 6-chlorouracil with amidines. A series of pyrimido [4,5-d]pyrimidines has been synthesized in good to excellent yields by the direct annulation of N-uracil amidines with benzaldehydes using Cs 2 CO 3 as base and molecular oxygen as oxidant in t BuOH at 100 0 C. This synthetic protocol has a number of advantages such asoperational simplicity, use of green oxidant, avoidance of transition metal catalysts or ligands, and easy accessibility of the starting materials, making it a highly practical approach to access various pyrimido [4,5-d]pyrimidines of biological interest.[a] Dr.

show abstract

“…Heterocycles containing pyrimidine scaffold (as a core unit) and their analogues have received considerable attentions due to their biological and pharmaceutical activities such as antibacterial, antileishmaniasis, antitumor and anti‐inflammatory . Furthermore, due to unique biological and pharmacological properties of pyrimido [4, 5‐b] quinoline derivatives such as antioxidant, antitumore and antiviral activities, synthesis of this class of compounds have gained great interest in synthetic organic chemistry. Recently, various methods were published for the synthesis of pyrimido [4, 5‐b] quinolintriones through multicomponent condensation reaction in the presence of different catalyst such as RuCl 3 , xH 2 O, tungstoposphoric acid (H 3 PW 12 O 40 ) under ultrasonic irradiation, TEBAC and [MSim]Cl ionic liquid .…”

Section: Introductionmentioning

confidence: 99%

Green and rapid synthesis of dihydropyrimido [4,5‐b]quinolinetrione derivatives using CoFe₂O₄@PPA as high efficient solid acidic catalyst under ultrasonic irradiation

Moradi

Mahdipour

2019

Applied Organom Chemis

View full text Add to dashboard Cite

A new high efficient and green protocol for the preparation of dihydropyrimido [4,5-b]quinolinetrione derivatives using magnetically solid acid catalyst was presented. High performance solid acid catalyst was prepared through a three-step reaction. Firstly, CoFe 2 O 4 nano particles were synthesized using co-precipitation method. In second step, CoFe 2 O 4 nano particles were coated with SiO 2 shell through treatment with tetraethyl orthosilicate (CoFe 2 O 4 @SiO 2 ). Finaly, CoFe 2 O 4 @SiO 2 was modified with polyphosphoric acid (CoFe 2 O 4 @SiO 2 /PPA) in a simple manner. Green reusable catalyst was characterized in details using FTIR, VSM, TEM, FESEM, EDX and used as catalyst for the synthesis of dihydropyrimido[4,5-b]quinolinetrione derivatives.Reaction was performed under ultrasonic irradiation as green, effective and mild conditions and products were achieved in high to excellent yields.Green and eco-friendly conditions, short reaction times with high yield of products in addition to easy workup are some merits of presented method. KEYWORDSCoFe 2 O 4 @SiO 2 /PPA, dihydropyrimido[4,5-b]quinolinetrione, green chemistry, solid acidic catalyst, ultrasonic irradiation

show abstract

Antitumor and antiviral activity of synthetic .alpha.- and .beta.-ribonucleosides of certain substituted pyrimido[5,4-d]pyrimidines: a new synthetic strategy for exocyclic aminonucleosides

Abstract: gel with 25:70:30:0.2 Me0H/CHCl3/H20/H0Ac afforded 112 mg (40%) of the amino ester, judged to be 90% pure by TLC and NMR. Rechromatography of a portion of this material as before

Cited by 70 publications

References 3 publications

Identifying the Novel Pyrimidine-Based CDK2 Inhibitors as Anticancer Agents Using Text-Mining and Combined Molecular Modeling Approaches

Identifying the Novel Pyrimidine-Based CDK2 Inhibitors as Anticancer Agents Using Text-Mining and Combined Molecular Modeling Approaches

Concise Pyrimido[4,5‐d]pyrimidine Synthesis via Direct Annulation of N‐Uracil Amidines with Benzaldehydes Under Transition Metal Free Conditions

Green and rapid synthesis of dihydropyrimido [4,5‐b]quinolinetrione derivatives using CoFe₂O₄@PPA as high efficient solid acidic catalyst under ultrasonic irradiation

Contact Info

Product

Resources

About

Antitumor and antiviral activity of synthetic .alpha.- and .beta.-ribonucleosides of certain substituted pyrimido[5,4-d]pyrimidines: a new synthetic strategy for exocyclic aminonucleosides

Abstract: gel with 25:70:30:0.2 Me0H/CHCl3/H20/H0Ac afforded 112 mg (40%) of the amino ester, judged to be 90% pure by TLC and NMR. Rechromatography of a portion of this material as before

Cited by 70 publications

References 3 publications

Identifying the Novel Pyrimidine-Based CDK2 Inhibitors as Anticancer Agents Using Text-Mining and Combined Molecular Modeling Approaches

Identifying the Novel Pyrimidine-Based CDK2 Inhibitors as Anticancer Agents Using Text-Mining and Combined Molecular Modeling Approaches

Concise Pyrimido[4,5‐d]pyrimidine Synthesis via Direct Annulation of N‐Uracil Amidines with Benzaldehydes Under Transition Metal Free Conditions

Green and rapid synthesis of dihydropyrimido [4,5‐b]quinolinetrione derivatives using CoFe2O4@PPA as high efficient solid acidic catalyst under ultrasonic irradiation

Contact Info

Product

Resources

About

Green and rapid synthesis of dihydropyrimido [4,5‐b]quinolinetrione derivatives using CoFe₂O₄@PPA as high efficient solid acidic catalyst under ultrasonic irradiation