Category: pyrimidines

Jansa, Petr published the artcileSynthesis and structure-activity relationship studies of polysubstituted pyrimidines as inhibitors of immune-activated nitric oxide production, Formula: C4H3Cl2N3, the publication is Medicinal Chemistry Research (2015), 24(5), 2154-2166, database is CAplus.

Based on the previous discovery of the inhibitory effect of the 5-substituted 2-amino-4,6-dichloropyrimidines on nitric oxide (NO) production in vitro, a series of novel pyrimidine derivatives, namely 4,6-dichloro-2-[(N,N-dimethylamino)methyleneamino]pyrimidines, 2,4-diamino-6-chloropyrimidines, and 2,4-diamino-6-(2-hydroxyethoxy)pyrimidines, were prepared bearing various substituents at the C-5 position on the pyrimidine, such as hydrogen, Me, Et, Pr, iso-Pr, propargyl, allyl, Bu, sec-Bu, Ph, benzyl, and fluorine. The intrinsic biol. potential of the prepared compounds was characterized by effects on the in vitro production of immune-activated NO in mouse peritoneal cells. All 5-substituted 4,6-dichloro-2-[(N,N-dimethylamino)methyleneamino]pyrimidines strongly inhibited NO production The IC₅₀s were <5 μM in most cases. The highest inhibitory activity was observed for the 5-s-Bu analog (IC₅₀ = 2.57 μM), the lowest one for 5-unsubstituted compound (IC₅₀ = 11.49 μM). With the exception of the 5-fluoro-4,6-dichloro-2-[(N,N-dimethylamino)methyleneamino] derivative, all other compounds were devoid of cytotoxic effects. The hitherto obtained data suggest that the NO-inhibitory activity depends on the presence of the 2-amino-4,6-dichloropyrimidine scaffold.

Medicinal Chemistry 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, Formula: C4H3Cl2N3.

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

Jansa, Petr published the artcile5-Substituted 2-amino-4,6-dihydroxypyrimidines and 2-amino-4,6-dichloropyrimidines. Synthesis and inhibitory effects on immune-activated nitric oxide production, Application In Synthesis of 56-05-3, the publication is Medicinal Chemistry Research (2014), 23(10), 4482-4490, database is CAplus and MEDLINE.

A series of 5-substituted 2-amino-4,6-dihydroxypyrimidines were prepared by a modified condensation of the corresponding monosubstituted malonic acid diesters with guanidine in an excess of sodium ethoxide. The optimized procedure using Vilsmeier-Haack-Arnold reagent, followed by immediate deprotection of the (dimethylamino)methylene protecting groups, was developed to convert the 2-amino-4,6-dihydroxypyrimidine analogs to novel 5-substituted 2-amino-4,6-dichloropyrimidines in high yields. Pilot screening for biol. properties of the prepared compounds was done in mouse peritoneal cells using the in vitro nitric oxide (NO) assay. Irresp. of the substituent at the 5 position, 2-amino-4,6-dichloropyrimidines inhibited immune-activated NO production The most effective was 5-fluoro-2-amino-4,6-dichloropyrimidine with an IC₅₀ of 2 μM (higher activity than the most potent reference compound) while the IC₅₀s of other derivatives were within the range of 9-36 μM. The 2-amino-4,6-dihydroxypyrimidine counterparts were devoid of any NO-inhibitory activity. The compounds had no suppressive effects on the viability of cells.

Medicinal Chemistry 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, Application In Synthesis of 56-05-3.

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

Westerlund, Kristina published the artcileDesign, Preparation, and Characterization of PNA-Based Hybridization Probes for Affibody-Molecule-Mediated Pretargeting, Synthetic Route of 169396-92-3, the publication is Bioconjugate Chemistry (2015), 26(8), 1724-1736, database is CAplus and MEDLINE.

In radioimmunotherapy, the contrast between tumor and normal tissue can be improved by using a pretargeting strategy with a primary targeting agent, which is conjugated to a recognition tag, and a secondary radiolabeled mol. binding specifically to the recognition tag. The secondary mol. is injected after the targeting agent has accumulated in the tumor and is designed to have a favorable biodistribution profile, with fast clearance from blood and low uptake in normal tissues. In this study, we have designed and evaluated two complementary peptide nucleic acid (PNA)-based probes for specific and high-affinity association in vivo. An anti-HER2 Affibody-PNA chimera, Z_HER2:342-SR-HP1, was produced by a semisynthetic approach using sortase A catalyzed ligation of a recombinantly produced Affibody mol. to a PNA-based HP1-probe assembled using solid-phase chem. A complementary HP2 probe carrying a DOTA chelator and a tyrosine for dual radiolabeling was prepared by solid-phase synthesis. CD (CD) spectroscopy and UV thermal melts showed that the probes can hybridize to form a structured duplex with a very high melting temperature (T_m), both in HP1:HP2 and in Z_HER2:342-SR-HP1:HP2 (T_m = 86-88 °C), and the high binding affinity between Z_HER2:342-SR-HP1 and HP2 was confirmed in a surface plasmon resonance (SPR)-based binding study. Following a moderately fast association (1.7 × 10⁵ M^-1 s^-1), the dissociation of the probes was extremely slow and <5% dissociation was observed after 17 h. The equilibrium dissociation constant (K_D) for Z_HER2:342-SR-HP1:HP2 binding to HER2 was estimated by SPR to be 212 pM, suggesting that the conjugation to PNA does not impair Affibody binding to HER2. The biodistribution profiles of ¹¹¹In- and ¹²⁵I-labeled HP2 were measured in NMRI mice, showing very fast blood clearance rates and low accumulation of radioactivity in kidneys and other organs. The measured radioactivity in blood was 0.63 ± 0.15 and 0.41 ± 0.15%ID/g for ¹²⁵I- and ¹¹¹In-HP2, resp., at 1 h p.i., and at 4 h p.i., the kidney accumulation of radioactivity was 0.17 ± 0.04%ID/g for ¹²⁵I-HP2 and 3.83 ± 0.39%ID/g for ¹¹¹In-HP2. Taken together, the results suggest that a PNA-based system has suitable biophys. and in vivo properties and is a promising approach for pretargeting of Affibody mols.

Bioconjugate Chemistry 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 C6H10O7, Synthetic Route of 169396-92-3.

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

Westerlund, Kristina published the artcileDesign, Preparation, and Characterization of PNA-Based Hybridization Probes for Affibody-Molecule-Mediated Pretargeting, Category: pyrimidines, the publication is Bioconjugate Chemistry (2015), 26(8), 1724-1736, database is CAplus and MEDLINE.

In radioimmunotherapy, the contrast between tumor and normal tissue can be improved by using a pretargeting strategy with a primary targeting agent, which is conjugated to a recognition tag, and a secondary radiolabeled mol. binding specifically to the recognition tag. The secondary mol. is injected after the targeting agent has accumulated in the tumor and is designed to have a favorable biodistribution profile, with fast clearance from blood and low uptake in normal tissues. In this study, we have designed and evaluated two complementary peptide nucleic acid (PNA)-based probes for specific and high-affinity association in vivo. An anti-HER2 Affibody-PNA chimera, Z_HER2:342-SR-HP1, was produced by a semisynthetic approach using sortase A catalyzed ligation of a recombinantly produced Affibody mol. to a PNA-based HP1-probe assembled using solid-phase chem. A complementary HP2 probe carrying a DOTA chelator and a tyrosine for dual radiolabeling was prepared by solid-phase synthesis. CD (CD) spectroscopy and UV thermal melts showed that the probes can hybridize to form a structured duplex with a very high melting temperature (T_m), both in HP1:HP2 and in Z_HER2:342-SR-HP1:HP2 (T_m = 86-88 °C), and the high binding affinity between Z_HER2:342-SR-HP1 and HP2 was confirmed in a surface plasmon resonance (SPR)-based binding study. Following a moderately fast association (1.7 × 10⁵ M^-1 s^-1), the dissociation of the probes was extremely slow and <5% dissociation was observed after 17 h. The equilibrium dissociation constant (K_D) for Z_HER2:342-SR-HP1:HP2 binding to HER2 was estimated by SPR to be 212 pM, suggesting that the conjugation to PNA does not impair Affibody binding to HER2. The biodistribution profiles of ¹¹¹In- and ¹²⁵I-labeled HP2 were measured in NMRI mice, showing very fast blood clearance rates and low accumulation of radioactivity in kidneys and other organs. The measured radioactivity in blood was 0.63 ± 0.15 and 0.41 ± 0.15%ID/g for ¹²⁵I- and ¹¹¹In-HP2, resp., at 1 h p.i., and at 4 h p.i., the kidney accumulation of radioactivity was 0.17 ± 0.04%ID/g for ¹²⁵I-HP2 and 3.83 ± 0.39%ID/g for ¹¹¹In-HP2. Taken together, the results suggest that a PNA-based system has suitable biophys. and in vivo properties and is a promising approach for pretargeting of Affibody mols.

Bioconjugate Chemistry 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 C6H10O7, Category: pyrimidines.

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

Kai, Hiroyuki published the artcileDiscovery of clinical candidate Sivopixant (S-600918): Lead optimization of dioxotriazine derivatives as selective P2X3 receptor antagonists, Name: 4-(2-Pyrimidinyloxy)aniline, the publication is Bioorganic & Medicinal Chemistry Letters (2021), 128384, database is CAplus and MEDLINE.

In previous work, we discovered a lead compound and conducted initial SAR studies on a novel series of dioxotriazines to identify the compound as one of the P2X3 receptor antagonists. This compound showed high P2X3 receptor selectivity and a strong analgesic effect. Although not selected for clin. development, the compound was evaluated from various aspects as a tool compound In the course of the following study, the mol. structures of the dioxotriazines were modified based on pharmacokinetic/pharmacodynamic (PK/PD) analyses. As a result of these SAR studies, Sivopixant (S-600918, I) was identified as a clin. candidate with potent and selective antagonistic activity (P2X3 IC₅₀, 4.2 nM; P2X2/3 IC₅₀, 1100 nM) and a strong analgesic effect in the rat partial sciatic nerve ligation model (Seltzer model) of allodynia (ED₅₀, 0.4 mg/kg).

Bioorganic & Medicinal Chemistry Letters published new progress about 105130-26-5. 105130-26-5 belongs to pyrimidines, auxiliary class Pyrimidine,Amine,Benzene,Ether, name is 4-(2-Pyrimidinyloxy)aniline, and the molecular formula is C10H9N3O, Name: 4-(2-Pyrimidinyloxy)aniline.

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

Huang, Kuo-Ting published the artcileCombinatorial Self-Assembly of Glycan Fragments into Microarrays, COA of Formula: C26H26N4O7, the publication is ChemBioChem (2011), 12(1), 56-60, database is CAplus and MEDLINE.

We have demonstrated that complex glycan arrays can be accessed through the combinatorial self assembly of PNA-encoded carbohydrate fragments. Although the use of DNA microarrays to sort carbohydrate-DNA conjugates had previously been reported, previous efforts were restricted to monosaccharides and did not explore a broad range of glycan structures, nor their combinatorial assembly. The cooperativity of the fragments in their interaction with carbohydrate-binding proteins was demonstrated with two different lectins. The binding profile showed the strongest interaction for discrete combinations of two fragments. Importantly, the PNA-tagged glycans can be readily prepared from native oligosaccharides obtained from natural or com. sources by conversion of the anomeric position into a thiol on a mg scale by a two- to three-step process. The simplicity of the protocols described should make glycan arrays more broadly accessible. Immobilization of glycans by hybridization offers a reliable approach by which to obtain a homogeneous distribution of ligands within a microarray spot and allows the use of microarrays with higher d. than accessible by contact printing, which is currently the standard practice. Last but not least, combinatorial self assembly of fragments on DNA microarrays should be broadly applicable beyond the glycan fragments described here.

ChemBioChem 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

Huang, Kuo-Ting published the artcileCombinatorial Self-Assembly of Glycan Fragments into Microarrays, Synthetic Route of 186046-81-1, the publication is ChemBioChem (2011), 12(1), 56-60, database is CAplus and MEDLINE.

We have demonstrated that complex glycan arrays can be accessed through the combinatorial self assembly of PNA-encoded carbohydrate fragments. Although the use of DNA microarrays to sort carbohydrate-DNA conjugates had previously been reported, previous efforts were restricted to monosaccharides and did not explore a broad range of glycan structures, nor their combinatorial assembly. The cooperativity of the fragments in their interaction with carbohydrate-binding proteins was demonstrated with two different lectins. The binding profile showed the strongest interaction for discrete combinations of two fragments. Importantly, the PNA-tagged glycans can be readily prepared from native oligosaccharides obtained from natural or com. sources by conversion of the anomeric position into a thiol on a mg scale by a two- to three-step process. The simplicity of the protocols described should make glycan arrays more broadly accessible. Immobilization of glycans by hybridization offers a reliable approach by which to obtain a homogeneous distribution of ligands within a microarray spot and allows the use of microarrays with higher d. than accessible by contact printing, which is currently the standard practice. Last but not least, combinatorial self assembly of fragments on DNA microarrays should be broadly applicable beyond the glycan fragments described here.

ChemBioChem 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, Synthetic Route of 186046-81-1.

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

Pianowski, Zbigniew published the artcileImaging of mRNA in Live Cells Using Nucleic Acid-Templated Reduction of Azidorhodamine Probes, Name: 2-(4-((tert-Butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid, the publication is Journal of the American Chemical Society (2009), 131(18), 6492-6497, database is CAplus and MEDLINE.

Nucleic acid-templated reactions leading to a fluorescent product represent an attractive strategy for the detection and imaging of cellular nucleic acids. Herein we report the use of a Staudinger reaction to promote the reduction of profluorescent azidorhodamine. The use of two cell-permeable GPNA probes, one labeled with the profluorescent azidorhodamine and the other with trialkylphosphine, enabled the detection of the mRNA encoding O-6-methylguanine-DNA methyltransferase in intact cells.

Journal of the American Chemical Society published new progress about 172405-16-2. 172405-16-2 belongs to pyrimidines, auxiliary class Pyrimidine,Carboxylic acid,Amine,Amide, name is 2-(4-((tert-Butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid, and the molecular formula is C11H15N3O5, Name: 2-(4-((tert-Butoxycarbonyl)amino)-2-oxopyrimidin-1(2H)-yl)acetic acid.

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

Rothlingshofer, Manuel published the artcileNucleic Acid-Templated Energy Transfer Leading to a Photorelease Reaction and its Application to a System Displaying a Nonlinear Response, Application In Synthesis of 169396-92-3, the publication is Journal of the American Chemical Society (2011), 133(45), 18110-18113, database is CAplus and MEDLINE.

The photocleavage of a nitrobenzyl-type linker (NPPOC) at 405 nm wavelength was enabled by nucleic acid-templated energy transfer from a sensitizer (thioxanthenone) to the linker. This strategy was used to release profluorescent rhodamine, which facilitated monitoring of the reaction via fluorescence measurement in a nonoverlapping window with the sensitizer/photocleavage reaction. The rate acceleration of the templated reaction was greater than 20-fold over the background reaction. The templated reaction was used in conjunction with strand displacement to design four-component systems that responded to an analyte (DNA). Programming a specific hierarchical relationship among the four components enabled the design of a system that responded first pos. and then neg. to increasing levels of an analyte.

Journal of the American Chemical Society 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, Application In Synthesis of 169396-92-3.

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

Rothlingshofer, Manuel published the artcileNucleic Acid-Templated Energy Transfer Leading to a Photorelease Reaction and its Application to a System Displaying a Nonlinear Response, Formula: C39H35N5O8, the publication is Journal of the American Chemical Society (2011), 133(45), 18110-18113, database is CAplus and MEDLINE.

The photocleavage of a nitrobenzyl-type linker (NPPOC) at 405 nm wavelength was enabled by nucleic acid-templated energy transfer from a sensitizer (thioxanthenone) to the linker. This strategy was used to release profluorescent rhodamine, which facilitated monitoring of the reaction via fluorescence measurement in a nonoverlapping window with the sensitizer/photocleavage reaction. The rate acceleration of the templated reaction was greater than 20-fold over the background reaction. The templated reaction was used in conjunction with strand displacement to design four-component systems that responded to an analyte (DNA). Programming a specific hierarchical relationship among the four components enabled the design of a system that responded first pos. and then neg. to increasing levels of an analyte.

Journal of the American Chemical Society 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, Formula: C39H35N5O8.

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