4551-03-5

Upstream product

• 120-57-0 piperonal 
• 74051-76-6 5-(benzo[d][1,3]dioxol-5-ylmethylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione 
• 67-52-7 BARBITURIC ACID 

Downstream Products

• 5463-73-0 5-(benzo[1,3]dioxol-5-ylmethyl)pyrimidine-2,4,6-trione 
• 1001318-01-9 3-(1,3-benzodioxol-5-yl)-2-phenyl-3,3a-dihydro-2H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)-dione 

Relevant academic research and scientific papers

Leucettamine B analogs and their carborane derivative as potential anti-cancer agents: Design, synthesis, and biological evaluation

Leucettamine B is a natural product found in marine sponge Leucetta microraphis. Several of analogs of its family, such as aplysinopsine and clathridine, are medicinally active molecules which have applications in many pharmaceuticals and healthcare products; however, thus far, leucettamine B has not been studied. In this report, we describe the synthesis of a new class of analogs of leucettamine B obtained by Knoevenagel condensation using a microwave reactor. The 25 newly synthesized compounds were tested against MDA-MB-468, SW480, and Mahlavu cell lines for anticancer activity. Among them, the carborane-based compound (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-3-(1-closo-carboranyl)-2-thioxo -thiazolidin-4-one (49) and (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-3-(2-(pyrrolidin-1-yl)ethyl)-2-thioxothiazolidin-4-one (31) derivatives were found to have the most potential for use against tumor cells. The carborane derivative 49 had the lowest IC50 value against the SW480 cell line (4.7 μM) and the Mahlavu (6.6 μM) cell line. Furthermore, compound 31 also had a low IC50 value against SW480 (7.5 μM). Our research shows that leucettamine B analogs might have potential for use in cancer chemotherapy.

Antifibrotic Effects of a Barbituric Acid Derivative on Liver Fibrosis by Blocking the NF-κB Signaling Pathway in Hepatic Stellate Cells

Hepatic stellate cells (HSCs) are the major profibrogenic cells that promote the pathogenesis of liver fibrosis. The crosstalk between transforming growth factor-β1 (TGF-β1) signaling and lipopolysaccharide (LPS)-induced NF-κB signaling plays a critical role in accelerating liver fibrogenesis. Until now, there have been no FDA-approved drug treatments for liver fibrosis. Barbituric acid derivatives have been used as antiasthmatic drugs in the clinic; however, the effect of barbituric acid derivatives in treating liver fibrosis remains unknown. In this study, we synthesized a series of six barbituric acid (BA) derivatives, and one of the compounds, BA-5, exhibited the best ability to ameliorate TGF-β1-induced HSC activation without overt cytotoxic effects. Then, we treated HSCs and RAW264.7 macrophages with BA-5 to analyze the cross-talk of anti-fibrotic and anti-inflammatory effects. Carbon tetrachloride (CCl4)-induced liver fibrosis mouse model was used to evaluate the therapeutic effects of BA-5. Treatment with BA-5 inhibited TGF-β1-induced α-SMA, collagen1a2, and phosphorylated smad2/3 expression in HSCs. Furthermore, BA-5 treatment reversed the LPS-induced reduction in BAMBI protein and decreased IκBα and NF-κB phosphorylation in HSCs. NF-κB nuclear translocation, MCP-1 secretion, and ICAM-1 expression were also inhibited in BA-5-treated HSCs. Conditioned medium collected from BA-5-treated HSCs showed a reduced ability to activate RAW264.7 macrophages by inhibiting the MAPK pathway. In the mouse model, BA-5 administration reduced CCl4-induced liver damage, liver fibrosis, and F4/80 expression without any adverse effects. In conclusion, our study showed that the barbituric acid derivative BA-5 inhibits HSCs activation and liver fibrosis by blocking both the TGF-β1 and LPS-induced NF-κB signaling pathways and further inhibits macrophages recruitment and activation.

Design, synthesis and in vivo evaluation of sodium 2-benzyl-chloromalonates as new central nervous system depressants

This work describes the design, synthesis and in vivo evaluation of new central nervous system depressing agents that show low levels of acute toxicity as well as high solubility in water and exhibit anxiolytic and hypnotic effects. These new compounds are sodium 2-benzyl-2-chloromalonates, which were designed using molecular modelling techniques and synthesized in four steps, with an overall yield between 41% and 65%. In vivo tests with mice, including pentobarbital-induced sleep, rotarod, open field and elevated plus maze tests, were carried out, and the results indicated that some of these agents induce activities similar to those induced by diazepam but with lower hypnotic potency and greater anxiolytic potency. These compounds were also orally administered to mice in doses of 2 g kg-1, and their effects were evaluated for 14 days. The mice did not show signs of intoxication, confirming that sodium 2-benzyl-2-chloromalonates exhibit low levels of acute toxicity. These observations indicate that sodium 2-benzyl-2-chloromalonates and their analogues are efficient and safer central nervous system depressing drugs relative to existing standards of care.

SHIKIMATE PATHWAY INHIBITORS AND THE USE THEREOF

The present invention relates to methods of inhibiting shikimate pathway, comprising administering to a subject a pharmaceutically acceptable composition comprising a compound having a formula: or pharmaceutically acceptable salts thereof. The present invention also provides a synergistic antibacterial composition containing compound

Barbituric acid in the synthesis of fused 1,7-phenanthroline derivatives

New 7-aryl(hetaryl)-7,8,9,10,11,12-hexahydropyrimido[5,4-b][1,7] phenanthroline-9,11-diones have been synthesized by three-component condensation of barbituric acid with quinolin-5-amine and aromatic or heteroaromatic aldehydes.

Synthesis and in vivo evaluation of 5-chloro-5-benzobarbiturates as new central nervous system depressants

A new family of barbiturates, 5-chloro-5-benzylbarbituric acids, was prepared using a simple efficient synthetic method from aromatic aldehydes and barbituric acid, followed by reduction and chlorination with trichloro-isocyanuric acid, affording overall yields of 53 to 70percent. The in vivo evaluation with mice showed that these compounds present tranquilizing activity.

SiO2?12WO3?24H2O: A highly efficient catalyst for the synthesis of 5-arylidene barbituric acid in the presence of water

The condensation of aromatic aldehydes and barbituric acid catalyzed by SiO212WO324H2O in aqueous media at room temperature gave 5-arylidene barbituric acid in high yields with or without the use of ultrasound, providing a simple and efficient route to synthesis of these compounds.

A new and efficient method for the synthesis of 5-arylmethylene- pyrimidine2,4,6-trione under solvent and catalyst free conditions

A new and efficient method has been developed for the synthesis of 5-arylmethylene-pyrimidine-2,4,6-trione without any catalyst and solvent under microwave irradiation. A number of condensation products are prepared in very short reaction time with high yields.

Organic reactions in ionic liquids: Ionic liquid promoted Knoevenagel condensation of aromatic aldehydes with (2-thio)barbituric acid

The Knoevenagel condensation of aromatic aldehydes with (2-thio)barbituric acid proceeded efficiently in reusable ionic liquids, EAN, BmimBF4, and BmimPF6 at room temperature in the absence of any catalyst with high yields.

Preparation of benzylidene barbituric acids promoted by infrared irradiation in absence of solvent

Several benzaldehydes were condensed with barbituric acid under infrared irradiation, in absence of solvent, affording the corresponding 5-benzylidene barbituric acids.