Month: November 2022

Fischbach, Melanie published the artcileProtease Probes that Enable Excimer Signaling upon Scission, Quality Control of 186046-81-1, the publication is Angewandte Chemie, International Edition (2014), 53(44), 11955-11959, database is CAplus and MEDLINE.

Peptide-based probes that fluoresce upon proteolytic cleavage are invaluable tools for monitoring protease activity. The read-out of protease activity through pyrene excimer signaling would be a valuable asset because the large Stokes shift and the long lifetime of the excimer emission facilitate measurements in autofluorescent media such as blood serum. However, proteolytic cleavage abolishes rather than installs the proximity relations required for excimer signaling. Herein, the authors introduce a new probe architecture to enable the switching on of pyrene excimer emission upon proteolytic scission. The method relies on hairpin-structured peptide nucleic acid (PNA)/peptide hybrids with pyrene units and anthraquinone-based quencher residues positioned in a zipper-like arrangement within the PNA stem. The excimer hairpin peptide beacons afforded up to a 50-fold enhancement of the pyrene excimer emission. Time-resolved measurements allowed the detection of matrix metalloprotease 7 in human blood serum.

Angewandte Chemie, International Edition published new progress about 186046-81-1. 186046-81-1 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(4-(((benzhydryloxy)carbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C39H35N5O8, Quality Control of 186046-81-1.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Fischbach, Melanie published the artcileProtease Probes that Enable Excimer Signaling upon Scission, COA of Formula: C26H26N4O7, the publication is Angewandte Chemie, International Edition (2014), 53(44), 11955-11959, database is CAplus and MEDLINE.

Peptide-based probes that fluoresce upon proteolytic cleavage are invaluable tools for monitoring protease activity. The read-out of protease activity through pyrene excimer signaling would be a valuable asset because the large Stokes shift and the long lifetime of the excimer emission facilitate measurements in autofluorescent media such as blood serum. However, proteolytic cleavage abolishes rather than installs the proximity relations required for excimer signaling. Herein, the authors introduce a new probe architecture to enable the switching on of pyrene excimer emission upon proteolytic scission. The method relies on hairpin-structured peptide nucleic acid (PNA)/peptide hybrids with pyrene units and anthraquinone-based quencher residues positioned in a zipper-like arrangement within the PNA stem. The excimer hairpin peptide beacons afforded up to a 50-fold enhancement of the pyrene excimer emission. Time-resolved measurements allowed the detection of matrix metalloprotease 7 in human blood serum.

Angewandte Chemie, International Edition published new progress about 169396-92-3. 169396-92-3 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide,Others,PNA, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido)acetic acid, and the molecular formula is C26H26N4O7, COA of Formula: C26H26N4O7.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Qiu, Yan published the artcileDesign and synthesis of uracil urea derivatives as potent and selective fatty acid amide hydrolase inhibitors, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is RSC Advances (2017), 7(37), 22699-22705, database is CAplus.

Fatty acid amide hydrolase (FAAH) is one of the key enzymes involved in the biol. degradation of endocannabinoids, especially anandamide. Pharmacol. blockage of FAAH restores the levels of endocannabinoids, providing therapeutic benefits in the management of inflammation, depression and multiple sclerosis. In this study, a series of uracil urea derivatives as FAAH inhibitors were designed and synthesized. Structural modifications at the C5 position and side chain of N-hexyl-2,4-dioxo-3,4-dihydropyrimidine-1(2H)-carboxamide (1a) led to FAAH inhibitors with improved potency and selectivity. Structure-activity relationship (SAR) studies indicated that C5 electron-withdrawing substituents were preferred for optimal potency but not for selectivity, whereas replacement of the alkyl chain with phenylalkyl moieties or biphenyl groups significantly improved both inhibitory potency and selectivity towards FAAH. Two highly potent picomolar FAAH inhibitors (4c, IC₅₀ = 0.3 ± 0.05 nM; 4d, IC₅₀ = 0.8 ± 0.1 nM) were developed. Compound 4c inhibited FAAH in a rapid, selective, noncompetitive, and irreversible pattern. This study provides several highly potent and selective FAAH inhibitors and an optimized chem. scaffold for the development of FAAH inhibitors. We anticipate that these FAAH inhibitors will enable new possibilities in understanding FAAH functions and development of therapeutics for pain and inflammatory diseases.

RSC Advances published new progress about 608-34-4. 608-34-4 belongs to pyrimidines, auxiliary class Pyrimidine,Amide, name is 3-Methylpyrimidine-2,4(1H,3H)-dione, and the molecular formula is C5H6N2O2, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Sana, Sravani published the artcileCinnamide derived pyrimidine-benzimidazole hybrids as tubulin inhibitors: Synthesis, in silico and cell growth inhibition studies, Recommanded Product: 2-Amino-4,6-dichloropyrimidine, the publication is Bioorganic Chemistry (2021), 104765, database is CAplus and MEDLINE.

A new class of piperazine-linked cinnamide derivatives of benzimidazole-pyrimidine hybrids have been synthesized and their in vitro cytotoxicity profiles were explored on selected human cancer cell lines. Specifically, structural comparison of target hybrids with tubulin-DAMA-colchicine and tubulin-nocodazole complexes has exposed a deep position of benzimidazole ring into the αT5 loop. The utmost cytotoxicity has shown with an amine linker of benzimidazole-pyrimidine series, with toward A549 (lung cancer) cell line. The most potent compound in this series was 18i, which inhibited cancer cell growth at micromolar concentrations ranging 2.21-7.29μM. Flow cytometry studies disclosed that compound I inhibited the cells in G2/M phase of cell cycle. The most active compound I also inhibited tubulin polymerization with an IC50 of 5.72 ± 0.51μM. In vitro biol. anal. of compound I presented apoptosis induction on A549 cells with triggering of ROS generation and loss of mitochondrial membrane potential, resulting in DNA injury. In addition, compound I displayed impairment in cellular migration and inhibited the colony formation. Notably, the safety profile of most potent compound 18i was revealed by screening against normal human pulmonary epithelial cells (L132: IC50: 69.25 ± 5.95μM). The detailed binding interactions of compound I with tubulin was investigated by employing mol. docking, superimposition and free energy analyses.

Bioorganic Chemistry published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Recommanded Product: 2-Amino-4,6-dichloropyrimidine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Sana, Sravani published the artcileExploration of carbamide derived pyrimidine-thioindole conjugates as potential VEGFR-2 inhibitors with anti-angiogenesis effect, Synthetic Route of 56-05-3, the publication is European Journal of Medicinal Chemistry (2020), 112457, database is CAplus and MEDLINE.

Here combined the two pharmacophoric units (pyrimidine and thioindole) combined in a single entity via mol. hybridization strategy along with introduction of urea functionality at C2 position of pyrimidine to increase the efficiency of H-bonding interactions. Among the synthesized conjugates I [R¹ = morpholino, piperidin-1-yl, phenylamino, etc.; R² = Ph, 4-methoxyphenyl, 4-chlorophenyl, etc.] compound I [R¹ = pyrrolidin-1-yl; R² = 4-chlorophenyl] was found to exhibited significant IC₅₀ =5.85, 7.87, 6.41 and 10.43μM against MDA-MB-231 (breast), HepG2 (liver), A549 (lung) and PC-3 (prostate) cancer cell lines, resp. All these compounds I were further evaluated for their inhibitory activities against VEGFR-2 protein. The results specified that among the tested compounds, I [R¹ = morpholino, R² = 2-methyl-4-chlorophenyl; R¹ = piperidin-1-yl, R² = 2,5-dimethylphenyl; R¹ = pyrrolidin-1-yl, R² = 4-chlorophenyl; R¹ = pyrrolidin-1-yl, R² = 2-methyl-4-chlorophenyl, R¹ = 4-(pyridin-2-yl)piperazin-1-yl, R² = 2-methyl-4-chlorophenyl; R¹ = 4-benzylpiperazin-1-yl, R² = Ph, 4-methoxyphenyl; R¹ = cyclopropylamino, R² = 2-methyl-4-chlorophenyl] prominently suppressed VEGFR-2, with IC₅₀ values of 310-920 nM in association to the pos. control (210 nM). Angiogenesis inhibition was evident by tube formation assay in HUVECs and cell-invasion by transwell assay. The mechanism of cellular toxicity on MDA-MB-231 was found through depolarization of mitochondrial membrane potential, increased ROS production and subsequent DNA damage resulting in apoptosis induction. Moreover, clonogenic and wound healing assays designated the inhibition of colony formation and cell migration by I [R¹ = pyrrolidin-1-yl; R² = 4-chlorophenyl] in a dose-dependent manner. Mol. docking studies also shown that compound I [R¹ = pyrrolidin-1-yl; R² = 4-chlorophenyl] capably intermingled with catalytically active residues GLU-885, ASP-1046 of the VEGFR-2 through hydrogen-bonding interactions.

European Journal of Medicinal Chemistry published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Synthetic Route of 56-05-3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Kheria, Sanjeev published the artcileThree in one: prototropy-free highly stable AADD-type self-complementary quadruple hydrogen-bonded molecular duplexes with a built-in fluorophore, Application In Synthesis of 56-05-3, the publication is Chemical Communications (Cambridge, United Kingdom) (2017), 53(18), 2689-2692, database is CAplus and MEDLINE.

This communication reports an effective approach for addressing the prototropy-related problems in heterocycle-based AADD-type self-assembling systems by freezing their hydrogen-bonding codes, by utilizing intramol. bifurcated hydrogen bonding interactions. Using this strategy, we have also developed a hydroquinone-conjugated AADD-type self-assembling system adorned with three valuable features such as prototropy-free dimerization yielding single duplexes, high duplex stability and a built-in fluorophore, which would augment its application potential. The rational approach used herein to arrest prototropic shift may also find application elsewhere, wherein proton shift-mediated structural changes become a detrimental factor.

Chemical Communications (Cambridge, United Kingdom) published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Application In Synthesis of 56-05-3.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Rajasekaran, S. published the artcileSynthesis and anti-denaturation activity of some substituted quinazolinone analogs, Safety of 2-Amino-4,6-dichloropyrimidine, the publication is International Journal of ChemTech Research (2012), 4(3), 1207-1211, database is CAplus.

In recent years there is a tremendous increase of inflammatory cases, leading to the design and development of newer anti-inflammatory agents. The reaction of 2-substituted phenyl-3-chloroacetamido quinazolin-4(3H)-ones with various 5-phenyl-1,3,4-oxadiazole-2-thiol and 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-thiol gave N-(4-oxo-2-substituted phenylquinazolin-3(4H)-yl)-2-[(5-aryl-1,3,4-oxadiazol-2-yl)sulfanyl] acetamides derivatives The reaction of 2-phenyl-3-chloroacetamido quinazolinone with various heteroaryl thiols and amines gave N-(4-oxo-2-Ph quinazolin-3(4H)-yl)-2-[(substituted amino/thiol)] acetamide derivatives The structure of all the compounds has been confirmed by IR, ¹HNMR, Mass spectral data and elemental anal. In vitro anti-inflammatory activity was performed by bovine serum albumin method. Some of the compounds have shown good antibacterial activity and few have shown moderate antioxidant activity compared to the standard drug.

International Journal of ChemTech Research published new progress about 56-05-3. 56-05-3 belongs to pyrimidines, auxiliary class Pyrimidine,Chloride,Amine,API, name is 2-Amino-4,6-dichloropyrimidine, and the molecular formula is C4H3Cl2N3, Safety of 2-Amino-4,6-dichloropyrimidine.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Augsburger, Fiona published the artcileRole of 3-mercaptopyruvate sulfurtransferase in the regulation of proliferation, migration, and bioenergetics in murine colon cancer cells, Category: pyrimidines, the publication is Biomolecules (2020), 10(3), 447, database is CAplus and MEDLINE.

The current study was designed to investigate the functional role of 3-MST’s catalytic activity in the murine colon cancer cell line CT26. The novel pharmacol. 3-MST inhibitor HMPSNE was used to assess cancer cell proliferation, migration and bioenergetics in vitro. Methods included measurements of cell viability (MTT and LDH assays), cell proliferation and in vitro wound healing (IncuCyte) and cellular bioenergetics (Seahorse extracellular flux anal.). 3-MST expression was detected by Western blotting; H₂S production was measured by the fluorescent dye AzMC. The results show that CT26 cells express 3-MST protein and mRNA, as well as several enzymes involved in H₂S degradation (TST, ETHE1). HMPSNE exerted a bell-shaped effect on several cellular bioenergetic parameters related to oxidative phosphorylation, while other bioenergeticparameterswereeitherunaffectedorinhibitedatthehighestconcentrationoftheinhibitor tested (300μM). In contrast to 3-MST, the expression of CBS (another H₂S producing enzyme which has been previously implicated in the regulation of various biol. parameters in other tumor cells) was not detectable in CT26 cells and pharmacol. inhibition of CBS exerted no significant effects on CT26 proliferation or bioenergetics. In summary, 3-MST catalytic activity significantly contributes to the regulation of cellular proliferation, migration and bioenergetics in CT26 murine colon cancer cells.

Biomolecules published new progress about 459420-09-8. 459420-09-8 belongs to pyrimidines, auxiliary class Metabolic Enzyme,3MST, name is 6-Methyl-2-((2-(naphthalen-1-yl)-2-oxoethyl)thio)pyrimidin-4(3H)-one, and the molecular formula is C17H14N2O2S, Category: pyrimidines.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Li, Nan published the artcileA Genetically Encoded Alkyne Directs Palladium-Mediated Protein Labeling on Live Mammalian Cell Surface, Name: 2-(Dimethylamino)pyrimidine-4,6-diol, the publication is ACS Chemical Biology (2015), 10(2), 379-384, database is CAplus and MEDLINE.

The merging of site-specific incorporation of small bioorthogonal functional groups into proteins via amber codon suppression with bioorthogonal chem. has created exciting opportunities to extend the power of organic reactions to living systems. A new alkyne amino acid can be site-selectively incorporated into mammalian proteins via a known orthogonal pyrrolysyl-tRNA synthetase/tRNA_CUA pair and directs an unprecedented, palladium-mediated cross-coupling reaction-driven protein labeling on live mammalian cell surface. A comparison study with the alkyne-encoded proteins in vitro indicated that this terminal alkyne is better suited for the palladium-mediated cross-coupling reaction than the copper-catalyzed click chem.

ACS Chemical Biology published new progress about 5738-14-7. 5738-14-7 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Alcohol,Pyrimidine, name is 2-(Dimethylamino)pyrimidine-4,6-diol, and the molecular formula is C6H9N3O2, Name: 2-(Dimethylamino)pyrimidine-4,6-diol.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia

Willwacher, Jens published the artcileSelective Metal-Site-Guided Arylation of Proteins, Category: pyrimidines, the publication is Journal of the American Chemical Society (2016), 138(28), 8678-8681, database is CAplus and MEDLINE.

We describe palladium-mediated S-arylation that exploits natural metal-binding motifs to ensure high site selectivity for a proximal reactive residue. This allows the chem. identification not only of proteins that bind metals but also the environment of the metal-binding site itself through proteomic anal. of arylation sites. The transformation is easy to perform under standard conditions, does not require the isolation of a reactive Ar-Pd complex, is broad in scope, and is applicable in cell lysates as well as to covalent inhibition/modulation of metal-dependent enzymic activity.

Journal of the American Chemical Society published new progress about 5738-14-7. 5738-14-7 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Alcohol,Pyrimidine, name is 2-(Dimethylamino)pyrimidine-4,6-diol, and the molecular formula is C6H13I, Category: pyrimidines.

Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/Pyrimidine,
Pyrimidine – Wikipedia