Day: October 20, 2022

Pithova, P.; Sorm, F. published the artcile< Influence of some derivatives and structural analogs of pyrimidine and purine bases on the degradation of uracil>, Safety of 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione, the main research area is .

The enzymic degradation of uracil (I) by rat liver Me2CO powder is inhibited by compounds possessing the NHCONH grouping in a 6-membered ring. Their activity, however, disappears on methylation of N. Xanthine, uric acid, orotie acid, 2-pyridone, and 5-bromo-6-azauracil inhibit the 1st stage of I degradation, viz., its reduction to dihydrouraeil (II). The inhibitory action of 5-substituted I derivatives is apparently of competitive character. None of the above compounds, however, inhibits the degradation of II and no accumulation of β-ureidopropionie acid and β-alanine was detected in the reaction mixture

Collection of Czechoslovak Chemical Communications published new progress about 4956-05-2. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Safety of 6-Bromo-1,2,4-triazine-3,5(2H,4H)-dione.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kang, Dongwei; Feng, Da; Sun, Yanying; Fang, Zengjun; Wei, Fenju; De Clercq, Erik; Pannecouque, Christophe; Liu, Xinyong; Zhan, Peng published the artcile< Structure-Based Bioisosterism Yields HIV-1 NNRTIs with Improved Drug-Resistance Profiles and Favorable Pharmacokinetic Properties>, Related Products of 18740-39-1, the main research area is thiophenepyrimidine piperidine substituted preparation antiHIV activity.

The development of efficacious NNRTIs for AIDS therapy commonly encountered the rapid generation of drug-resistant mutations, which becomes a major impediment to effective anti-HIV treatment. Using a structure-based bioisosterism strategy, a series of piperidine-substituted thiophene[2,3-d]pyrimidine derivatives were designed and synthesized. Compound I yielded the greatest potency, exhibiting significantly better anti-HIV-1 activity than ETR against all of the tested NNRTI-resistant HIV-1 strains. In addition, the phenotypic (cross)resistance of I and other NRTIs to the different selected HIV-1 strains was evaluated. As expected, no phenotypic cross-resistance against the NRTIs (AZT and PMPA) was observed with the mutant Ires strain. Furthermore, I was identified with improved solubility, lower CYP liability, and hERG inhibition. Remarkably, I exhibited optimal pharmacokinetic properties in rats (F = 37.06%) and safety in mice (LD50 > 2000 mg/kg), which highlights I as a promising anti-HIV-1 drug candidate.

Journal of Medicinal Chemistry published new progress about Anti-HIV agents. 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Related Products of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ferris, J. P.; Joshi, P. C.; Lawless, J. G. published the artcile< Chemical evolution. XXIX. Pyrimidines from hydrogen cyanide>, Related Products of 15837-41-9, the main research area is pyrimidine formation prebiosis; hydrogen cyanide pyrimidine formation.

Dilute (0.1M) solutions of HCN condensed to oligomers at pH 8-9. Hydrolysis of these oligomers at pH 8.5 or with 6N HCl yielded 4,5-dihydroxypyrimidine as the most abundant pyrimidine product along with orotic acid and 5-hydroxyuracil. Thus, the 3 major N-containing classes of biomols. could have originated from HCN on the primitive earth. The observation of the formation of orotic acid and 4-aminoimidazole-5-carboxamide by the hydrolysis of the HCN oligomers suggested that once the initially formed pyrimidines and purines were consumed, those life forms persisted which evolved enzymes for the conversion of these intermediates to the pyrimidines and purines present in contemporary RNA.

BioSystems published new progress about Molecular evolution. 15837-41-9 belongs to class pyrimidines, and the molecular formula is C4H4N2O2, Related Products of 15837-41-9.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kabbaj, Youssef; Lazrek, Hassan Bihi; Barascut, Jean Louis; Imbach, Jean Louis published the artcile< Synthesis and biological activity of some unsaturated 6-aza-uracil acyclo-nucleosides>, Category: pyrimidines, the main research area is HIV antiviral acyclic nucleoside preparation human alkylation azauracil condensation.

A useful route is described for obtaining Z and E unsaturated alkylating agents, e.g. AcOCH2CH:CHCH2Br. Coupling 6-aza-uracil I (X = H, Br, R = H) with unsaturated alkylating agent followed by the deprotection with acid resin gave acyclo-nucleosides, e.g. (E and Z)-I (X = H, Br; R = Ch2CH:CHCH2OH), in good overall yields. Unsaturated acyclo-nucleosides phosphonates, e.g. II (X = H, Br), were prepared using potassium carbonate as base and 4-bromo-but-2-enyl di-Et phosphonate as the alkylating agent. The introduction of a propargyl group at the N-3 position of acyclo-nucleosides was achieved using potassium carbonate in DMF. Title 6-aza-uracil acyclo-nucleosides were tested for their in vitro antiviral activity. II (X = H, Br) showed activity at 7 μg/mL, but they were also very toxic at this concentration

Nucleosides, Nucleotides & Nucleic Acids published new progress about Acyclonucleosides Role: BSU (Biological Study, Unclassified), RCT (Reactant), SPN (Synthetic Preparation), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation). 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Bretschneider, H.; Richter, W.; Kloetzer, W. published the artcile< New reactions of sulfonamides. XV. Syntheses of 4-sulfanilamido-5,6-dimethoxypyrimidine>, SDS of cas: 5018-38-2, the main research area is .

4,6-Dihydroxy-5-methoxypyrimidine (I), m. 275-80°, was prepared (a) as the Na salt from di-Me α-methoxymalonate (II) and HC-(:NH)NH2 in MeOH-NaOMe, (b) by desulfurizing the 2-mercapto- derivative, m. 215° (decomposition) (from II and CS(NH2)2]. In 4,6-dichloro-5-methoxypyrimidine (III), m. 57-8° (from I and POCl3), one Cl atom reacts readily with nucleophiles; III with liquid NH3 at 20 atm. gave 4-amino- (IV), m. 178-80°, with Na sulfanilamide in HCONMe2 at 100° 4-sulfanilamido- (V), m. 198-202° (190°, labile form), with Na N-4-acetylsulfanilamide in HCONMe2 at 100° 4-(N-4-acetylsulfanilamido)-5-methoxy-6-chloropyrimidine (VI), m. 210-12°, and with NaOMe-MeOH at 20° 4-chloro-5,6-dimethoxypyrimidine (VII), m. 53-5°. V autoclaved at 125° with NaOMe-MeOH gave the title compound (VIII), m. 192-4° (4:1 MeOH-H2O). VI was hydrolyzed by boiling 0.5N NaOH to V, and by NaOMe-MeOH at 115-25° (autoclave) to VIII. VII in EtOH with PhSNa or EtSNa gave 4-phenylthio; b0.001 160-70°, or 4-ethylthio-5,6-dimethoxypyrimidine, b0.05, 84°, oxidized by peracetic acid to the corresponding 4-phenylsulfonyl-, m. 96-100° (EtOH-H2O, 1:1) and 4-ethylsulfonyl-5,6-dimethoxypyrimidine, m. 87-8° (EtOH-H2O); both sulfones yielded VIII when heated with Na sulfanilamide. Autoclaved at 130° with NaOMe-MeOH III was converted to 4,5,6-trimethoxypyrimidine, m. 56-8°. Other routes to VIII started from Me 2-methoxy-2-cyanoacetate (from the bromo ester and CuCN), b25 99°, n20D 1.4170, which with CS(NH2)2 afforded 2-mercapto-4-amino-5-methoxy-6-hydroxypyrimidine (IX), m. 275-80° (decomposition); desulfurized IX, m. 230-1°, with POCl3 gave IV, converted by p-acetamidobenzenesulfonyl chloride via the disulfonyl derivative (not isolated) to VIII. Alternatively, IX was S-methylated by MeI-NaOMe and the 2-methylthio derivative, m. 203°, treated with PhMe3N toluenesulfonate to give (beside an N-Me derivative, m. 206-7°) 2-methylthio-4-amino-5,6-di-methoxypyrimidine, m. 115-17°, the p-acetamidobenzenesulfonyl derivative, m. 220-1°, which was desulfurized (Raney Ni) and deacetylated to VIII. VIII was investigated as a potential antibacterial agent with prolonged action similar to its 2,6-dimethoxy congener.

Monatshefte fuer Chemie published new progress about Sulfonamides. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, SDS of cas: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Li, Ruoxi; Ling, Dazheng; Tang, Tongke; Huang, Zhenghui; Wang, Manjiong; Ding, Yan; Liu, Taiping; Wei, Hanwen; Xu, Wenyue; Mao, Fei; Zhu, Jin; Li, Xiaokang; Jiang, Lubin; Li, Jian published the artcile< Discovery of Novel Plasmodium falciparum HDAC1 Inhibitors with Dual-Stage Antimalarial Potency and Improved Safety Based on the Clinical Anticancer Drug Candidate Quisinostat>, Safety of Ethyl 2-chloropyrimidine-5-carboxylate, the main research area is Plasmodium HDAC HDAC1 inhibitors antimalarials antitumor drug repurposing.

Previously, we identified the clin. anticancer drug candidate quisinostat as a novel and potent antimalarial lead compound To further enhance the antimalarial effect and improve safety, 31 novel spirocyclic hydroxamic acid derivatives were synthesized based on the structure of quisinostat, and their antimalarial activities and cytotoxicity were evaluated. Among them, compound 11 displayed broad potency in vitro against several multi-resistant malarial parasites, especially two artemisinin-resistant clin. isolates. Moreover, 11 could eliminate both liver and erythrocytic parasites in vivo, kill all morphol. erythrocytic parasites with specific potency against schizonts, and show acceptable metabolic stability and pharmacokinetic properties. Western blot anal., PfHDAC gene knockdown, and enzymic inhibition experiments collectively confirmed that PfHDAC1 was the target of 11. In summary, 11 is a structurally novel PfHDAC1 inhibitor with the potential to prevent and cure malaria, overcome multi-drug resistance, and provide a prospective prototype for antimalarial drug research.

Journal of Medicinal Chemistry published new progress about Acetylation (hyperacetylation). 89793-12-4 belongs to class pyrimidines, and the molecular formula is C7H7ClN2O2, Safety of Ethyl 2-chloropyrimidine-5-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Chambers, Richard D.; Musgrave, W. Kenneth R.; Wood, David E. published the artcile< Polyhaloaromatic compounds. Part 30. Eliminations of molecular nitrogen from trichloro- and perfluorotri-isopropyl-1,2,4-triazine>, Reference of 4956-05-2, the main research area is elimination nitrogen chlorotriazine fluoroisopropyltriazine; triazine chloro fluoroisopropyl nitrogen elimination.

3,5,6-Trichloro-1,2,4-triazine (I; R = Cl) with CF3CF:CF2 and KF gave 61% I [R = (CF3)2CF]. Gas-phase pyrolysis of I (R = Cl) gave CCl2:CClCN, indicating an intermediate azete. Pyrolysis of I [R = (CF3)2CF] gave a mixture of (CF3)2CFCCCF(CF3)2 (II) and (CF3)2CFCN, whereas photolysis resulted in rearrangement to the triazine III in addition to formation of II and (CF3)2CFCN via elimination of N.

Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999) published new progress about Elimination reaction. 4956-05-2 belongs to class pyrimidines, and the molecular formula is C3H2BrN3O2, Reference of 4956-05-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Allehyani, Basmah H.; Elroby, Shaaban A.; Aziz, Saadullah G.; Hilal, Rifaat H. published the artcile< Protonation and deprotonation enthalpies of alloxan and implications for the structure and energy of its complexes with water: a computational study>, Product Details of C4H4N2O5, the main research area is alloxan water complex hydrogen bond DFT calculation; DFT calculations; alloxan; dipolar alloxan–water interaction; gas phase acidities; hydrogen bond; trajectory dynamics simulation.

The optimized geometries, harmonic vibrational frequencies, and energies of the structures of monohydrated alloxan were computed at the DFT/ωB97X-D and B3LYP/6-311++G** level of theory. Results confirm that the monohydrate exists as a dipolar alloxan-water complex which represents a global min. on the potential energy surface (PES). Trajectory dynamics simulations show that attempt to reorient this monohydrate, to a more favorable orientation for H-bonding, is opposed by an energy barrier of 25.07 kJ/mol. Alloxan seems to prefer acting as proton donor than proton acceptor. A marked stabilization due to the formation of N-H-OH2 bond is observed The concerted proton donor-acceptor interaction of alloxan with one H2O mol. does not increase the stability of the alloxan-water complex. The proton affinity of the O and N atoms and the deprotonation enthalpy of the NH bond of alloxan are computed at the same level of theory. Results are compared with recent data on uracil, thymine, and cytosine. The intrinsic acidities and basicities of the four pyrimidines were discussed. Results of the present study reveal that alloxan is capable of forming stronger H-bonds and more stable cyclic complex with water, yet it is of much lower basicity than other pyrimidines.

Journal of Biomolecular Structure and Dynamics published new progress about Atomic charge. 2244-11-3 belongs to class pyrimidines, and the molecular formula is C4H4N2O5, Product Details of C4H4N2O5.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Son, Hoon Young; Song, Yang-Heon published the artcile< A convenient synthesis of new 3,7-diphenylthieno[3,2-e]bis[1,2,4]triazolo[4,3-a:4',3'-c]pyrimidine derivatives by oxidative cyclization using alumina-supported calcium hypochlorite>, Synthetic Route of 18740-39-1, the main research area is thienopyrimidinylhydrazone oxidative cyclization alumina supported calcium hypochlorite; thienoditriazolopyrimidine preparation.

New 3,7-diphenylthieno[3,2-e]bis[1,2,4]triazolo[4,3-a:4′,3′-c]pyrimidine derivatives were easily synthesized at room temperature in good yield by the oxidative cyclization of thienopyrimidinylhydrazones with Al2O3-supported Ca(OCl)2.

Bulletin of the Korean Chemical Society published new progress about Fused heterocyclic compounds Role: SPN (Synthetic Preparation), PREP (Preparation). 18740-39-1 belongs to class pyrimidines, and the molecular formula is C6H2Cl2N2S, Synthetic Route of 18740-39-1.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Le, Phuong T.; Richardson, Paul F.; Sach, Neal W.; Xin, Shuibo; Ren, Shijian; Xiao, Jiezhan; Xue, Liangliang published the artcile< Development of a Scalable Synthesis of 4-Aminopyrimidin-5-ol, a Versatile Intermediate>, SDS of cas: 5018-38-2, the main research area is aminopyrimidinol preparation green chem.

A robust process for the preparation of multigram quantities of 4-aminopyrimidin-5-ol in good yield from an inexpensive and readily available 4,6-dichloro-5-methoxypyrimidine starting material is described. An initial evaluation of the reported literature route for this material utilizing a de novo pyrimidine synthesis provided safety concerns over the scalability of several intermediates. In addition, a number of steps proceeded in mediocre yield, and involved chromatog. separations for the desired products. The newly developed route mitigates the safety concerns, reduces the number of steps from five to three, avoids column chromatog., leads to an 8-fold improvement in yield, and utilizes reagents, which are recognized to be more environmentally benign.

Organic Process Research & Development published new progress about Green chemistry. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, SDS of cas: 5018-38-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia