294197-68-5

Upstream product

• 4397-53-9 p-benzyloxybenzaldehyde 
• 141-97-9 ethyl acetoacetate 
• 57-13-6 urea 
• 123-08-0 4-hydroxy-benzaldehyde 
• 123629-41-4 ethyl 4-(4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 
• 100-39-0 benzyl bromide 
• 100-52-7 benzaldehyde 

Relevant academic research and scientific papers

RETRACTED ARTICLE: Boric acid in magnetized water: Clean and powerful media for synthesis of 3,4-dihydropyrimidin-2(1: H)-ones

Water was magnetized via an external magnetic field and employed, for the first time, as a solvent in green preparation of 3,4-dihydropyrimidin-2(1H)-ones by the one-pot three-component condensation reaction using boric acid as a catalyst. Shorter reactio

Synthesis and in vitro study of antiproliferative benzyloxy dihydropyrimidinones

In this study, we report on antiproliferative benzyloxy dihydropyrimidinones (DHPMs) produced by the Biginelli reaction of benzyloxy benzaldehyde, urea, and diverse 1,3-diones. The reaction was catalyzed by lanthanum triflate and completed within 1–1.5 h,

Nickel Chloride Hexahydrate Catalyzed Multicomponent Biginelli's Synthesis of 3,4-Dihydropyrimidin-2(1H)-Ones and Thiones

An efficient protocol is reported for the one-pot three-component Bignelli synthesis of a series of 3,4-dihydropyrimidine-2(1H)-ones and thiones in good yields (66–90%) from the aldehydes (4-benzyloxybenzaldehyde, 5-bromovanilin, 4-formyl-1-cyclohexene, a

Discovery and structural optimization of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-ones as RORc inverse agonists

Aim: Retinoic acid receptor-related orphan nuclear receptors (RORs) are orphan nuclear receptors that show constitutive activity in the absence of ligands. Among 3 subtypes of RORs, RORc is a promising therapeutic target for the treatment of Th17-mediated autoimmune diseases. Here, we report novel RORc inverse agonists discovered through structure-based drug design. Methods: Based on the structure of compound 8, a previously described agonist of RORa, a series of 4-(4-(benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-one derivatives were designed and synthesized. The interaction between the compounds and RORc was detected at molecular level using AlphaScreen assay. The compounds were further examined in 293T cells transfected with RORc and luciferase reporter gene. Thermal stability shift assay was used to evaluate the effects of the compounds on protein stability. Results: A total of 27 derivatives were designed and synthesized. Among them, the compound 22b was identified as the most potent RORc inverse agonist. Its IC50 values were 2.39 μmol/L in AlphaScreen assay, and 0.82 μmol/L in inhibition of the cell-based luciferase reporter activity. Furthermore, the compound 22b displayed a 120-fold selectivity for RORc over other nuclear receptors. Moreover, a molecular docking study showed that the structure-activity relationship was consistent with the binding mode of compound 22b in RORc. Conclusion: 4-(4-(Benzyloxy)phenyl)-3,4-dihydropyrimidin-2(1H)-one derivatives are promising candidates for the treatment of Th17-mediated autoimmune diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.

Identification of new nonsteroidal RORα ligands; Related structure-activity relationships and docking studies

A high throughput screen was developed to identify novel, nonsteroidal RORα agonists. Among the validated hit compounds, the 4-(4-(benzyloxy) phenyl)-5-carbonyl-2-oxo-1,2,3,4-tetrahydropyrimidine scaffold was the most prominent. Among the numerous analogues tested, compounds 8 and 9 showed the highest activity. Key structure-activity relationships (SAR) were established, where benzyl and urea moieties were both identified as very important elements to maintain the activity. Most notably, the SAR were consistent with the binding mode of the compound 8 (S-isomer) in the RORα docking model that was developed in this program. As predicted by the model, the urea moiety is engaged in the formation of key hydrogen bonds with the backbone of Tyr380 and Asp382. The benzyl group is located in a wide hydrophobic pocket. The structural relationships reported in this letter will help in further optimization of this compound series and will provide novel synthetic probes helpful for elucidation of complex RORα physiopathology.