7269-15-0

Upstream product

• 4270-27-3 6-chlorouracil 
• 62-53-3 aniline 
• 67-52-7 BARBITURIC ACID 

Downstream Products

• 84459-37-0 8-chloro-10-phenyl-2H,3H,4H,10H-pyrimido[4,5-b]quinoline-2,4-dione 
• 84459-38-1 8-Hydroxy-10-phenyl-10H-pyrimido[4,5-b]quinoline-2,4-dione 
• 87750-74-1 10-Phenyl-1H,10H-pyrimido[5,4-g]pteridine-2,4,6,8-tetraone 
• 87750-77-4 7-Methyl-10-phenyl-1H,10H-pyrimido[5,4-g]pteridine-2,4,6,8-tetraone 
• 84459-36-9 7-nitro-10-phenyl-2H,3H,4H,10H-pyrimido[4,5-b]quinoline-2,4-dione 
• 84459-35-8 10-phenyl-2H,3H,4H,10H-pyrimido[4,5-b]quinoline-2,4-dione 
• 1079130-18-9 C₃₈H₄₉N₃O₂ 
• 1257251-81-2 7'-phenyl-3H-spiro[isobenzofuran-1,6'-pyrrolo[2,3-d]pyrimidine]-2',3,4',5'(1'H,3'H,7'H)-tetraone 
• 6851-14-5 10-phenylbenzo[g]pteridine-2,4(3H,10H)-dione 
• 1448807-55-3 7-chloro-10-phenyl-2H,3H,4H,10H-pyrimido[4,5-b]quinoline-2,4-dione 

Relevant academic research and scientific papers

Novel Deazaflavin Analogues Potently Inhibited Tyrosyl DNA Phosphodiesterase 2 (TDP2) and Strongly Sensitized Cancer Cells toward Treatment with Topoisomerase II (TOP2) Poison Etoposide

Topoisomerase II (TOP2) poisons as anticancer drugs work by trapping TOP2 cleavage complexes (TOP2cc) to generate DNA damage. Repair of such damage by tyrosyl DNA phosphodiesterase 2 (TDP2) could render cancer cells resistant to TOP2 poisons. Inhibiting TDP2, thus, represents an attractive mechanism-based chemosensitization approach. Currently known TDP2 inhibitors lack cellular potency and/or permeability. We report herein two novel subtypes of the deazaflavin TDP2 inhibitor core. By introducing an additional phenyl ring to the N-10 phenyl ring (subtype 11) or to the N-3 site of the deazaflavin scaffold (subtype 12), we have generated novel analogues with considerably improved biochemical potency and/or permeability. Importantly, many analogues of both subtypes, particularly compounds 11a, 11e, 12a, 12b, and 12h, exhibited much stronger cancer cell sensitizing effect than the best previous analogue 4a toward the treatment with etoposide, suggesting that these analogues could serve as effective cellular probes.

UV365 light promoted catalyst-free synthesis of pyrimido[4,5-b] quinoline-2,4-diones in aqueous-glycerol medium

Herein, a highly efficient and environmentally benign protocol for the synthesis of biologically important pyrimido[4,5-b]quinolinone-2,4-diones from aromatic amines, barbituric acid and aryl aldehyde is reported. This process takes place at room temperat

Aggregation effects in visible-light flavin photocatalysts: Synthesis, structure, and catalytic activity of 10-arylflavins

A series of 10-arylflavins (10-phenyl-, 10-(2′,6′- dimethylphenyl)-, 10-(2′,6′-diethylphenyl)-, 10-(2′,6′- diisopropylphenyl)-, 10-(2′-tert-butylphenyl)-, and 10-(2′,6′- dimethylphenyl)-3-methylisoalloxazine (2 a-f)) was prepared as potentially nonaggrega

Synthesis and biological evaluation of novel pyrimido[4,5-b]quinoline-2,4- dione derivatives as MDM2 ubiquitin ligase inhibitors

A series of pyrimido[4,5-b]quinoline-2,4-dione derivatives was synthesized and evaluated for their cytotoxic activities in vitro against five human cancer cell lines. Selected compounds were tested for their MDM2 E3 ligase inhibitory activities and p53-MDM2 binding inhibitory activities. Among tested compounds, four sulfur-containing compounds (4-7) displayed enhanced cytotoxic activities and better MDM2 E3 ligase inhibitoty activities in comparison with that of HLI98c. Three compounds (4-6) showed better p53-MDM2 binding inhibitory potency with IC50 values ranging from 1.3 μM to 9.0 μM.

Toxoflavins and deazaflavins as the first reported selective small molecule inhibitors of tyrosyl-DNA phosphodiesterase II

The recently discovered enzyme tyrosyl-DNA phosphodiesterase 2 (TDP2) has been implicated in the topoisomerase-mediated repair of DNA damage. In the clinical setting, it has been hypothesized that TDP2 may mediate drug resistance to topoisomerase II (topo II) inhibition by etoposide. Therefore, selective pharmacological inhibition of TDP2 is proposed as a novel approach to overcome intrinsic or acquired resistance to topo II-targeted drug therapy. Following a high-throughput screening (HTS) campaign, toxoflavins and deazaflavins were identified as the first reported sub-micromolar and selective inhibitors of this enzyme. Toxoflavin derivatives appeared to exhibit a clear structure-activity relationship (SAR) for TDP2 enzymatic inhibition. However, we observed a key redox liability of this series, and this, alongside early in vitro drug metabolism and pharmacokinetics (DMPK) issues, precluded further exploration. The deazaflavins were developed from a singleton HTS hit. This series showed distinct SAR and did not display redox activity; however low cell permeability proved to be a challenge.

5-Deazaflavin derivatives as inhibitors of p53 ubiquitination by HDM2

Based on previous reports of certain 5-deazaflavin derivatives being capable of activating the tumour suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2, we have conducted an structure-activity relationship (SAR) analysis through systematic modification of the 5-deazaflavin template. This analysis shows that HDM2-inhibitory activity depends on a combination of factors. The most active compounds (e.g., 15) contain a trifluoromethyl or chloro substituent at the deazaflavin C9 position and this activity depends to a large extent on the presence of at least one additional halogen or methyl substituent of the phenyl group at N10. Our SAR results, in combination with the HDM2 RING domain receptor recognition model we present, form the basis for the design of drug-like and potent activators of p53 for potential cancer therapy.

Synthesis, biological active molecular design, and molecular docking study of novel deazaflavin-cholestane hybrid compounds

Novel deazaflavin-cholestane hybrid compounds, 3′,8′-disubstituted-5′-deazacholest-2,4-dieno[2,3-g]pteridine-2′,4′(3′H,8′H)-diones, have been synthesized by condensation reaction between 6-(monosubstituted amino)-pyrimidin-2,4(1H,3H)-diones and 2-hydroxymethylenecholest-4-en-3-one in presence of p-toluenesulfonic acid monohydrate and diphenyl ether. The antitumor activities against human tumor cell lines (CCRF-HSB-2 and KB cells) have been investigated in vitro, and many of these compounds showed promising antitumor activities. Furthermore, molecular docking study using LigandFit within the software package Discovery Studio 1.7 was done for lead optimization of these compounds as potential PTK inhibitors. In general, all of the synthesized steroid-hybrid compounds showed good binding affinities into PTK (PDB code: 1t46).

Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells

A family of 5-deazaflavin derivatives has been synthesised using a two-step convergent strategy. The biological activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low molecular weight inhibitors of the E3 activity of HMD2 in tumours that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1-3 (HL198C-E)] is not essential for observation of this biological activity.

Synthesis of substituted uracils by the reactions of halouracils with selenium, sulfur, oxygen and nitrogen nucleophiles under focused microwave irradiation

Under microwave irradiation, the nucleophilic substitution reactions of halouracils with selenium, sulfur, oxygen and nitrogen nucleophiles was complete within several minutes with yields up to 99%. The method using microwave irradiation is superior to th

Microwave-assisted facile one-step carbamoylation of 6-aminouracils

Carbamoylation of 6-aminouracils was achieved by reacting 6-aminouracils with isocyanates under computer-controlled microwave irradiation for a short reaction time. Under known thermal conditions, most of carbamoylated uracils are obtained in poor yields