Day: November 21, 2022

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

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

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

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

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

Brown, D. J. published the artcileSimple pyrimidines. III. Methylation and structure of the aminopyrimidines, Application of N,N-Dimethylpyrimidin-4-amine, the publication is Journal of the Chemical Society (1955), 4035-40, database is CAplus.

cf. C.A. 49, 14000f. 2- (I) and 4-aminopyrimidine (II) were shown to exist largely in the amino form, by comparison of their basic strength, and ultraviolet and infrared spectra with those of the corresponding nuclear and extranuclear N-Me derivatives The preparation of the nuclear N-Me derivatives involved the methylation of I and II to 1,2-dihydro-2- (III) and 1,4-dihydro-4-imino-1-methylpyrimidine (IV), resp. In alk. solution, III rearranged to 2-methylaminopyrimidine (V), while IV was hydrolyzed to 1,4-dihydro-1-methyl-4-oxopyrimidine (VI). The ultraviolet spectra of the cations of I and II were similar to those of the cations of III and IV, which suggested that a proton was bonded to a nuclear N atom in cations from I and II. This view was suggested by the marked difference between the spectra of the cations of I, II, V, 2-dimethylamino (VII), 4-methylamino- (VIII), and 4-dimethylaminopyrimidine (IX) and that of the neutral mol. of pyrimidine itself. For the neutral molecules of I and II the ultraviolet absorption curves were quantitatively displaced along the wavelength scale from those of the corresponding nuclear N-Me derivatives (III and IV) than from those of the extranuclear N-Me analogs V, VII, VIII, and IX. There is the possibility of some amine-imine tautomerism. The extent of such tautomerism was calculated from the ionization constants of the N-Me series fixed in the amino and imino forms. K_tautometric = [amine]/(imine] = K_a[amino]/K_a[imino]. By using the ionization constants of III, IV, V, VII, VIII, and IX it was found that the amine-imine tautomeric constant in aqueous solution was of the order of 10⁶ for both I and II. In the solid state and in nonaqueous solvents I and II similarly exist largely in the amino form as was shown by their infrared spectra. Both I and II in CCl₄ gave 2 sharp bands at 3540 and 3430 cm.^-1 due to asym. and sym. stretching modes of the unassocd. NH₂ group and 2 broad bands at 3320 and 3170 cm.^-1 due to vibration modes of the intermol. H-bonded NH₂ group. V and VIII give only 1 sharp band at 3460 cm.^-1 and a broad one near 3260 cm.^-1 In the double-bond stretching region, I and II showed a strong band at 1650 cm.^-1 which was due to internal deformation of the NH₂ group, for it disappeared upon deuteriation. In the same region the salts of III and IV absorbed strongly at 1646 cm.^-1 and the deuteriated compounds showed some absorption, which may be due to the C:N stretching mode. V and VIII showed a strong band near 1615 cm.^-1 and were unaffected by deuteriation. I (5 g.), 10 ml. MeI, and 60 ml. MeOH were kept 5 days at room temperature to give 2.9 g. III hydriodide (X), m. 247-8° (decomposition) (from 95% EtOH). X (0.23 g.) cooled to 0°, moistened with H₂O, covered with Et₂O, and then ground with 1 g. powd. KOH and the Et₂O solution separated, dried, and concentrated yielded crude III. Recrystallization of III was carried out by solution in Et₂O, drying, filtering through cotton, concentrating, cooling to room temperature, filtering with a filter stick, and drying in a desiccator over CaCl₂ to yield pure III, yellow needles, m. 102-4°; picrate, m. 198-200° (from EtOH). X (1 g.) heated 10 min. in 12 ml. NaOH solution yielded 71% V, m. 59-60°; picrate, m. 191° (mixed m.p. with III picrate showed a depression). II (5 g.), 5 ml. MeI, and 25 ml. MeOH refluxed 1 hr. gave 10 g. IV hydriodide (XI), m. 205-6° (from EtOH). In another experiment the reactants were left 3 days at room temperature to give XI, m. 163-4°. Recrystallization of this lower-melting form or storage for 3 days gave the higher-melting form. XI picrate, m. 172-3° (from EtOH). XI (0.9 g.) left 10 hrs. at 20-5° with 0.1N NaOH, HCl added to pH 5, the solution evaporated and the residue treated with picric acid yielded 55% VI picrate, m. 164-6°. VI picrate, prepared from authentic base also m. 164-6°. The 2 specimens showed no mixed m.p. depression. An attempt to prepare 1,2,3,4-tetrahydro-2,4-diimino-1,3-dimethylpyrimidine gave only a single monomethylated derivative of indeterminate structure.

Journal of the Chemical Society published new progress about 31401-45-3. 31401-45-3 belongs to pyrimidines, auxiliary class Pyrimidine,Amine, name is N,N-Dimethylpyrimidin-4-amine, and the molecular formula is C6H9N3, Application of N,N-Dimethylpyrimidin-4-amine.

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

Wandlowski, Th. published the artcileStructural and Thermodynamic Aspects of Phase Transitions in Uracil Adlayers. A Chronocoulometric Study, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione, the publication is Langmuir (1996), 12(26), 6604-6615, database is CAplus.

The phase formation of uracil and 5 uracil alkyl derivatives on a Au (111) single crystal electrode from aqueous 0.05 M KClO₄ was studied by using chronocoulometry, cyclic voltammetry, and phase-sensitive ac voltammetry. As a function of the applied electrode potential and/or the adsorbate concentration, uracil (U), 5-methyluracil (5-MU), and 5,6-dimethyluracil (5,6-DMU) exhibit 4 different adsorption regions. These are assigned to a “dilute” phase (I), a 2-dimensional condensed physisorbed film (II), a partial charge transfer/deprotonation region (III), and a chemisorbed film (IV). Substitution of the N (1)- and/or the N (3)-ring N with Me groups prevents the formation of the ordered physisorbed film II. In the case of 1-methyluracil (1-MU) and 3-methyluracil (3-MU), region I is followed immediately by regions III and IV. No indications for the latter 2 regions were found with 1,3-dimethyluracil, where both ring N atoms are blocked simultaneously with Me groups. Quant. thermodn. adsorption parameters (e.g., film pressure, Gibbs surface excess, Gibbs energy of adsorption, and electrosorption valence) were determined on the basis of chronocoulometric measurements for the “dilute” and the 2-dimensional condensed physisorbed film. All of these mols. are oriented parallel to the electrode surface in both ordered regions. The corresponding values of the Gibbs energies of adsorption ΔG_I° and ΔG_II° of the 6 uracil derivatives on Au (111) indicate weak chemisorption. On the basis of structural and energetic data, the formation of the 2D-condensed physisorbed film of U, 5-MU, and 5,6-DMU is interpreted as a replacement of residual interfacial H₂O mols. accompanied by the creation of a 2D network of planar oriented and (via H bonds) interconnected mols. The adsorption and phase formation parameter obtained for the 6 uracil derivatives on Au (111) in regions I and II is complemented by anal. of selected (published) results on Ag (111) and Hg electrodes. No quant. thermodn. data were extracted in regions III and IV.

Langmuir 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 C19H14Cl2, Recommanded Product: 3-Methylpyrimidine-2,4(1H,3H)-dione.

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

Schleper, A. Lennart published the artcileInfluence of regioisomerism in bis(terpyridine) based exciplexes with delayed fluorescence, Product Details of C4H3Cl2N3, the publication is Journal of Materials Chemistry C: Materials for Optical and Electronic Devices (2022), 10(19), 7699-7706, database is CAplus.

Exciplexes of individual electron donor and acceptor mols. are a promising approach to utilizing otherwise non-emissive triplet states in optoelectronic applications. In this work, we synthesize a series of bis(terpyridine) pyrimidine (BTP) isomers and employ them as electron acceptors in complexes with tris(4-carbazoyl-9-ylphenyl)amine (TCTA). We show that these TCTA : BTP complexes produce thermally activated delayed fluorescence (TADF) by exciplex emission, and we investigate the influence of the nitrogen position in the pyridine on the optical and electronic properties of the exciplex. The mol. arrangement of the complex is studied using scanning tunneling microscopy (STM) as well as classical force field and d. functional theory (DFT) simulations. Finally, we fabricate organic light-emitting diodes (OLEDs) with maximum external quantum efficiencies ranging between 0.5% and 2% – depending on the BTP isomer.

Journal of Materials Chemistry C: Materials for Optical and Electronic Devices 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, Product Details of C4H3Cl2N3.

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

Latham, Jonathan published the artcileIntegrated catalysis opens new arylation pathways via regiodivergent enzymatic C-H activation, Recommanded Product: 2-(Dimethylamino)pyrimidine-4,6-diol, the publication is Nature Communications (2016), 11873pp., database is CAplus and MEDLINE.

The integration of regioselective halogenase enzymes with Pd-catalyzed cross-coupling chem., in one-pot reactions, successfully addresses this problem for the indole heterocycle was demonstrated. The resultant ‘chemobio-transformation’ delivered a range of functionally diverse arylated products that were impossible to access using sep. enzymic or chemocatalytic C-H activation, under mild, aqueous conditions. This use of different biocatalysts to select different C-H positions contrasts with the prevailing substrate-control approach to the area, and presented opportunities for new pathways in C-H activation chem. The issues of enzyme and transition metal compatibility were overcome through membrane compartmentalization, with the optimized process requiring no intermediate work-up or purification steps.

Nature Communications 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, Recommanded Product: 2-(Dimethylamino)pyrimidine-4,6-diol.

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

Gompper, Rudolf published the artcileAminopyridines, aminopyrimidines, and tris(dimethylamino) benzene from (aza) vinamidinium and (aza)pentamethinium salts, Application of N,N-Dimethylpyrimidin-4-amine, the publication is Angewandte Chemie (1981), 93(3), 298-9, database is CAplus.

Reaction of H₂XC(NMe₂):N⁺:CRNMe₂.ClO₄^– (X = CH, R = H, Ph, Me, NMe₂; X = N, R = H) with Me₂NCH(OEt)₂ gave 74-90% Me₂NCH:XC(NMe₂):N⁺:CRNMe₂.ClO₄^– (I). I (X = CH) were cyclized with NH₄OAc to give the pyrimidines II (R = H, Ph, NMe₂). The pyridine III was obtained by treating I (X = CH, R = Me) with base. 1,3,5-(Me₂N)₃C₆H₃ was obtained in 70% yield by treating Me₂NCMe:C:C(NMe₂)₂.HClO₄ with Me₂NCMe(OEt)₂.

Angewandte Chemie published new progress about 31401-45-3. 31401-45-3 belongs to pyrimidines, auxiliary class Pyrimidine,Amine, name is N,N-Dimethylpyrimidin-4-amine, and the molecular formula is C6H9N3, Application of N,N-Dimethylpyrimidin-4-amine.

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