36822-11-4

Usage

Uses

Used in Pharmaceutical Industry:
6-PHENYL-2-THIOURACIL is used as a reference material for the development and optimization of thyreostatic drug separation and detection technologies. Its application is crucial in ensuring the accuracy and reliability of these technologies, which are essential for the analysis and quality control of thyreostatic drugs.
Used in Analytical Chemistry:
6-PHENYL-2-THIOURACIL is used as a reference compound in various analytical techniques such as capillary electrophoresis, high-performance liquid chromatography (HPLC), and gas chromatography. These techniques are employed to separate, identify, and quantify thyreostatic drugs in samples, and the use of 6-PHENYL-2-THIOURACIL as a reference material helps to standardize the methods and improve their performance.
Used in Research and Development:
6-PHENYL-2-THIOURACIL is also used in research and development for the study of thyroid hormone regulation and the development of new thyreostatic drugs. Its role as a reference material allows researchers to compare the properties and effectiveness of newly synthesized compounds with established standards, facilitating the advancement of knowledge in this field.

InChI:InChI=1/C10H8N2OS/c13-9-6-8(11-10(14)12-9)7-4-2-1-3-5-7/h1-6H,(H2,11,12,13,14)

Upstream product

• 1147550-11-5 ammonium thiocyanate 
• 94-02-0 ethyl 3-oxo-3-phenylpropionate 
• 17356-08-0 thiourea 
• 73921-19-4 5-benzoyl-2,2-dimethyl-1,3-dioxane-4,6-dione 
• 93-58-3 benzoic acid methyl ester 
• 614-27-7 methyl 3-oxo-3-phenylpropionate 
• 100-52-7 benzaldehyde 
• 141-78-6 ethyl acetate 

Downstream Products

• 56035-29-1 2-methylthio-6-phenyl-3,4-dihydropyrimidin-4-one 
• 99072-62-5 6-phenyl-3,4-dihydro-1H-pyrimidine-2-thione 
• 13345-09-0 6-phenyluracil 
• 64247-58-1 6-phenylpyrimidine-2,4(1H,3H)-dithione 
• 86799-26-0 2-hydrazineyl-6-phenylpyrimidin-4(3H)-one 
• 4891-69-4 4-phenyl-6(1H)-pyrimidinone 
• 29558-46-1 7-phenyl-2,3-dihydro-thiazolo[3,2-a]pyrimidin-5-one 
• 74303-68-7 3-methyl-2-(methylsulfanyl)-6-phenylpyrimidin-4(3H)-one 
• 102649-60-5 2-(methylthio)-4-methoxy-6-phenylpyrimidine 
• 102649-61-6 2-(methylthio)-1-methyl-6-phenyl-4(3H)-pyrimidinone 

Relevant academic research and scientific papers

New 2,4-disubstituted-2-thiopyrimidines as VEGFR-2 inhibitors: Design, synthesis, and biological evaluation

A new series of 2,4-disubstituted-2-thiopyrimidines 6a–t, 9a, and 9b was efficiently designed and synthesized as antiangiogenic and cytotoxic agents. Compounds 6j, 6l, and 6d showed IC50 values of 1.23, 3.78, and 3.84 μM, respectively, against the vascular endothelial growth factor receptor-2 (VEGFR-2). Most of the synthesized 2-thiouracils showed antiproliferative activity against the HepG2 cell line (hepatocellular carcinoma) in the micromolar range, for instance, 9b, 6l, 6m, 6n, and 6j displayed IC50 = 7.92, 8.35, 8.51, 9.59, and 13.06 μM, respectively, relative to sorafenib (III; IC50 = 10.99 μM). Also, compounds 6j, 9a, 6m, and 6s (IC50 = 15.21, 16.96, 17.68, and 18.15 μM, respectively) are the most potent compounds against the UO-31 cell line. Further evaluation of the effect of the synthesized candidates on VEGFR-2 in the HepG2 cell line demonstrated that compounds 6j and 6l exhibit VEGFR-2 inhibitory activity of 87% and 84%, respectively, relative to sorafenib (III; 92%). In silico docking of the synthesized hits into the binding site of VEGFR-2 showed their ability to perform the main binding interactions with the key amino acids in the binding site. Studying the in silico predicted ADME (absorption, distribution, metabolism, and excretion) parameters for the synthesized thiouracils demonstrated that they have favorable pharmacokinetic and drug-likeness properties. These results demonstrate that the 2,4-disubstituted thiouracils 6 and 9 have not only favorable antiangiogenic and antiproliferative activity but also satisfy the criteria required for the development of orally bioavailable drugs. Consequently, they represent a biologically active scaffold that should be further optimized for future discovery of potential hits.

Antitubercular 2-Pyrazolylpyrimidinones: Structure-Activity Relationship and Mode-of-Action Studies

Phenotypic screening of a Medicines for Malaria Venture compound library against Mycobacterium tuberculosis (Mtb) identified a cluster of pan-active 2-pyrazolylpyrimidinones. The biology triage of these actives using various tool strains of Mtb suggested a novel mechanism of action. The compounds were bactericidal against replicating Mtb and retained potency against clinical isolates of Mtb. Although selected MmpL3 mutant strains of Mtb showed resistance to these compounds, there was no shift in the minimum inhibitory concentration (MIC) against a mmpL3 hypomorph, suggesting mutations in MmpL3 as a possible resistance mechanism for the compounds but not necessarily as the target. RNA transcriptional profiling and the checkerboard board 2D-MIC assay in the presence of varying concentrations of ferrous salt indicated perturbation of the Fe-homeostasis by the compounds. Structure-activity relationship studies identified potent compounds with good physicochemical properties and in vitro microsomal metabolic stability with moderate selectivity over cytotoxicity against mammalian cell lines.

Structure optimization of positive allosteric modulators of GABAB receptors led to the unexpected discovery of antagonists/potential negative allosteric modulators

Positive allosteric modulators (PAMs) of GABAB receptor represent an interesting alternative to receptor agonists such as baclofen, as they act on the receptor in a more physiological way and thus are devoid of the side effects typically exerted by the agonists. Based on our interest in the identification of new GABAB receptor PAMs, we followed a merging approach to design new chemotypes starting from selected active compounds, such as GS39783, rac-BHFF, and BHF177, and we ended up with the synthesis of four different classes of compounds. The new compounds were tested alone or in the presence of 10 μM GABA using [35S]GTPγS binding assay to assess their functionality at the receptor. Unexpectedly, a number of them significantly inhibited GABA-stimulated GTPγS binding thus revealing a functional switch with respect to the prototype molecules. Further studies on selected compounds will clarify if they act as negative modulators of the receptor or, instead, as antagonists at the orthosteric binding site.

Pyrimidone molecule for promoting SOD activity in cosmetics and preparation method and application thereof

The invention discloses a pyrimidone molecule for prompting the SOD activity in cosmetics and a preparation method and application thereof, and belongs to the technical field of synthesis of proteaseagonists. According to the technical scheme, the molecule is characterized in that the pyrimidone molecule is of the structure shown in the specification, methyl benzoate with the low cost is adoptedas a starting raw material, and the novel pyrimidone molecule of the novel structure can be obtained through condensation substitution, ring formation, chlorination, cyanogroup substitution, aethrization and other poly-step reactions. The molecule is easy and rapid to operate, high in yield and suitable for industrial mass production, can effectively improve the activity of SOD in cosmetics, and has the potential as a domestic auxiliary additive.

α-Amino-β-carboxymuconate-?-semialdehyde Decarboxylase (ACMSD) Inhibitors as Novel Modulators of de Novo Nicotinamide Adenine Dinucleotide (NAD+) Biosynthesis

NAD+ has a central function in linking cellular metabolism to major cell-signaling and gene-regulation pathways. Defects in NAD+ homeostasis underpin a wide range of diseases, including cancer, metabolic disorders, and aging. Although the beneficial effects of boosting NAD+ on mitochondrial fitness, metabolism, and lifespan are well established, to date, no therapeutic enhancers of de novo NAD+ biosynthesis have been reported. Herein we report the discovery of 3-[[[5-cyano-1,6-dihydro-6-oxo-4-(2-thienyl)-2-pyrimidinyl]thio]methyl]phenylacetic acid (TES-1025, 22), the first potent and selective inhibitor of human ACMSD (IC50 = 0.013 μM) that increases NAD+ levels in cellular systems. The results of physicochemical-property, ADME, and safety profiling, coupled with in vivo target-engagement studies, support the hypothesis that ACMSD inhibition increases de novo NAD+ biosynthesis and position 22 as a first-class molecule for the evaluation of the therapeutic potential of ACMSD inhibition in treating disorders with perturbed NAD+ supply or homeostasis.

Discovery of wtRET and V804MRET Inhibitors: From Hit to Lead

Oncogenic activation of RET kinase has been found in several neoplastic diseases, like medullary thyroid carcinoma, multiple endocrine neoplasia, papillary thyroid carcinoma, and non-small-cell lung cancer. Currently approved RET inhibitors were not originally designed to be RET inhibitors, and their potency against RET kinase has not been optimized. Hence, novel compounds able to inhibit both wild-type RET (wtRET) and its mutants (e.g., V804MRET) are needed. Herein we present the development and the preliminary evaluation of a new sub-micromolar wtRET/V804MRET inhibitor, N-(2-fluoro-5-trifluoromethylphenyl)-N′-{4′-[(2′′-benzamido)pyridin-4′′-ylamino]phenyl}urea (69), endowed with a 4-anilinopyridine structure, starting from our previously identified 4-anilinopyrimidine hit compound. Profiling against a panel of kinases indicated 69 as a multi cKIT/wtRET/V804MRET inhibitor.

INHIBITORS OF α-AMINO-β-CARBOXYMUCONIC ACID SEMIALDEHYDE DECARBOXYLASE

The present disclosure discloses compounds capable of modulating the activity of α-amino-β-carboxymuconic acid semialdehyde decarboxylase (ACMSD), which are useful for the prevention and/or the treatment of diseases and disorders associated with defects in NAD+ biosynthesis, e.g., metabolic disorders, neurodegenerative diseases, chronic inflammatory diseases, kidney diseases, and diseases associated with ageing. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament.

Synthesis and biological evaluation of novel pyrimidine-benzimidazol hybrids as potential anticancer agents

A series of pyrimidine-benzimidazol hybrids was synthesized and evaluated for anticancer activity on four human cancer cell lines including MCF-7, MGC-803, EC-9706 and SMMC-7721. Some of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 5a-b and 6a-b showed most effective activity. Compounds 5b and 6b were more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines, with IC50 values ranging from 2.03 to 10.55 μM and 1.06 to 12.89 μM, respectively. Flow cytometry analysis demonstrated that treatment of MGC-803 with 6b led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death.

Synthesis and antitumor activity evaluation of pyrimidine analogues bearing urea moiety

A series of 4-anilino-6-phenylpyrimidines containing urea moiety were synthesized and the structures of all products were confirmed by 1H NMR, 13C NMR and HRMS. The antiproliferative activities of these compounds were evaluated against three human tumor cell lines (MGC-803, MCF-7 and EC-109) by applying the MTT assay method. compounds 4a, 4b and 6a showed the most effective activity, among which, 6a was more cytotoxic than 5-fluorouracil against all tested human cancer cell lines with IC50 values ranging from 1.80 to 2.72 μmol·L-1. A series of 4-anilino-6-phenylpyrimidines containing urea moiety were synthesized. The antiproliferative activities of these compounds were evaluated against three human tumor cell lines (MGC-803, MCF-7 and EC-109) by applying the MTT assay method. compounds 4a, 4b and 6a showed most effective activity, among which, 6a was more cytotoxic than 5-fluorouracil against all tested three human cancer cell lines with IC50 values ranging from 1.80 to 2.72 μmol·L-1. Copyright

Evaluation of a large library of (thiazol-2-yl)hydrazones and analogues as histone acetyltransferase inhibitors: Enzyme and cellular studies

Recently we described some (thiazol-2-yl)hydrazones as antiprotozoal, antifungal and anti-MAO agents as well as Gcn5 HAT inhibitors. Among these last compounds, CPTH2 and CPTH6 showed HAT inhibition in cells and broad anticancer properties. With the aim to identify HAT inhibitors more potent than the two prototypes, we synthesized several new (thiazol-2-yl)hydrazones including some related thiazolidines and pyrimidin-4(3H)-ones, and we tested the whole library existing in our lab against human p300 and PCAF HAT enzymes. Some compounds (1x, 1c', 1d', 1i' and 2m) were more efficient than CPTH2 and CPTH6 in inhibiting the p300 HAT enzyme. When tested in human leukemia U937 and colon carcinoma HCT116 cells (100 μM, 30 h), 1x, 1i' and 2m gave higher (U937 cells) or similar (HCT116 cells) apoptosis than CPTH6, and were more potent than CPTH6 in inducing cytodifferentiation (U937 cells).