Month: November 2022

Li, Jian-Yuan published the artcilePalladium-Catalyzed Hydroxycarbonylation of (Hetero)aryl Halides for DNA-Encoded Chemical Library Synthesis, Synthetic Route of 60703-80-2, the main research area is palladium catalyzed hydroxycarbonylation heteroaryl halide DNA encoded library synthesis.

A strategy for DNA-compatible, palladium-catalyzed hydroxycarbonylation of (hetero)aryl halides on DNA-chem. conjugates has been developed. This method generally provided the corresponding carboxylic acids in moderate to very good conversions for (hetero)aryl iodides and bromides, and in poor to moderate conversions for (hetero)aryl chlorides. These conditions were further validated by application within a DNA-encoded chem. library synthesis and subsequent discovery of enriched features from the library in selection experiments against two protein targets.

Bioconjugate Chemistry published new progress about Carbonylation. 60703-80-2 belongs to class pyrimidines, name is 6-Bromothieno[2,3-d]pyrimidine, and the molecular formula is C6H3BrN2S, Synthetic Route of 60703-80-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Devine, Shane M. published the artcileA critical evaluation of pyrrolo[2,3-d]pyrimidine-4-amines as Plasmodium falciparum apical membrane antigen 1 (AMA1) inhibitors, Category: pyrimidines, the main research area is pyrrolopyrimidineamine derivative antimalarial AMA1 inhibitor Plasmodium malaria.

We have determined that a previously reported class of pyrrolo[2,3-d]pyrimidine-4-amines exhibit low binding to apical membrane antigen 1 (AMA1) and suffer from unattractive qualities, such as aggregation. We attempted to remove these traits by generating mols. with improved solubility, but this did not translate into enhanced binding affinity or inhibition of parasite growth in erythrocytes. These results indicate that anti-malarial activity is not primarily due to inhibition of AMA1 function, but mediated by an alternate or addnl. mechanism of action.

MedChemComm published new progress about Antimalarials. 1266343-30-9 belongs to class pyrimidines, name is 5-Bromo-4-chloro-7-methyl-7H-pyrrolo[2,3-d]pyrimidine, and the molecular formula is C7H5BrClN3, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Yamanaka, Hiroshi published the artcileStudies on pyrimidine derivatives. XXXIX. Site-selectivity in the reaction of 5-substituted and 4,5-disubstituted pyrimidine N-oxides with trimethylsilyl cyanide, Quality Control of 38275-56-8, the main research area is Reissert Henze pyrimidine oxide regiochem; methylsilyl cyanide pyrimidine oxide reaction; pyrimidinecarbonitrile.

The site-selectivity in the modified Reissert-Henze reaction of pyrimidine 1-oxides I (R = OMe, R1 = Ph, Me, OMe, Br, Cl) with Me3SiCN gave pyrimidinecarbonitriles II (R = OMe, same R1, R2 = H, R3 = cyano) in 53-95% yields, whereas I (R = H, Ph, Me, same R1) gave mainly II (R = H, Ph, Me, same R1, R2 = cyano, R3 = H).

Chemical & Pharmaceutical Bulletin published new progress about Regiochemistry. 38275-56-8 belongs to class pyrimidines, name is 5-Chloropyrimidine-2-carbonitrile, and the molecular formula is C5H2ClN3, Quality Control of 38275-56-8.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Yamagami, Chisako published the artcileHydrophobicity parameter of diazines. 1. Analysis and prediction of partition coefficients of monosubstituted diazines, Computed Properties of 42839-08-7, the main research area is hydrophobicity diazine LFER; partition coefficient diazine.

The octanol/water partition coefficient (P) of a number of monosubstituted diazines was measured. The composition of the π value of substituents, the increment in the log P value accompanying the introduction of substituents, was examined in terms of physicochem. substituent parameters and correlation anal. The diazine-π value of substituents was generally higher than the pyridine-π value of corresponding substituents, indicating that the intramol. electronic interactions between the ring-N atoms and substituent are more pronounced than those in substituted pyridines in governing the log P value of the mol. Except for 2-substituted pyrimidines, the π value of substituents in each series of monosubstituted diazines was in general nicely correlated with the π value of the corresponding substituents in substituted pyridines along with electronic parameter terms representing bidirectional electronic effects on the relative solvation of the ring-N atom(s) and the hydrogen-bondable substituents with partitioning solvents according to the procedure proposed previously for the anal. of the π value in disubstituted benzenes and monosubstituted pyridines. Keeping in mind that 2-pyrimidines substituted by hydrogen-bondable groups sometimes behave as outliers, the correlations were believed to be usable for prediction of log P values of monosubstituted diazines.

Quantitative Structure-Activity Relationships published new progress about Hydrophobicity. 42839-08-7 belongs to class pyrimidines, name is Ethyl pyrimidine-2-carboxylate, and the molecular formula is C7H8N2O2, Computed Properties of 42839-08-7.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Summa, Vincenzo published the artcile4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species, Quality Control of 519028-33-2, the main research area is pyrimidinecarboxamide derivative preparation HIV integrase structure activity.

The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. The optimization of physicochem. properties, pharmacokinetic profiles, and potency led to the identification of (I) in the dihydroxypyrimidine series and (II) in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclin. species.

Journal of Medicinal Chemistry published new progress about AIDS (disease). 519028-33-2 belongs to class pyrimidines, name is Benzyl (2-(4-((4-fluorobenzyl)carbamoyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-yl)carbamate, and the molecular formula is C23H23FN4O5, Quality Control of 519028-33-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Miazga, Agnieszka published the artcileSynthesis and anti-HIV properties of novel 6-phenylselenenyl-5-propyluracils, Computed Properties of 19030-75-2, the main research area is phenylselenenylpropyluracil preparation antiHIV antiviral antiHIV antiAIDS.

Novel 6-phenylselenenyl-5-propyluracils were synthesized from 5-propyluracil with the use of regioselective synthesis to give 1-[(2-hydroxyethoxy)methyl]-6-phenylselenenyl-5-propyluracil (6), 1-ethoxymethyl-6-phenylselenenyl-5-propyluracil (9) and 1-benzyloxymethyl-6-phenylselenenyl-5-propyluracil (10). Interaction of these compounds with recombinant HIV-1 reverse transcriptase (RT) was evaluated using a non-isotopic colorimetric method. Compounds 9 and 10 exerted potent HIV RT inhibition (IC50 = 0.06 and 0.05 μM resp.) while compound 6 showed moderate inhibition (IC50 = 3.5 μM). Potent anti-HIV-1 activity in MT-2 cells inoculated by a syncythia-inducing HIV-1 (cat #3 strain) laboratory isolate was exerted by compounds 9 and 10 (EC50 = 0.62 μM and 0.025 μM, resp.), while compound 6 showed only moderate activity (IC50 = 4.1 μM). In addition, compound 10 showed very good in vitro therapeutic index (TI > 2046), indicating that it is a potential anti-HIV/AIDS drug.

Acta Biochimica Polonica published new progress about AIDS (disease). 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, Computed Properties of 19030-75-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Reddy, G. S. Kiran Kumar published the artcileDesign and Synthesis of HIV-1 Protease Inhibitors Incorporating Oxazolidinones as P2/P2′ Ligands in Pseudosymmetric Dipeptide Isosteres, Recommanded Product: (S)-3-Methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoic acid, the main research area is phenyloxazolidinone dipeptide isostere preparation inhibitor HIV1 protease antiviral.

A series of novel HIV-1 protease inhibitors based on two pseudosym. dipeptide isosteres have been synthesized and evaluated. The inhibitors were designed by incorporating N-phenyloxazolidinone-5-carboxamides into the hydroxyethylene and (hydroxyethyl)hydrazine dipeptide isosteres as P2 and P2′ ligands. Compounds with (S)-phenyloxazolidinones attached at a position proximal to the central hydroxyl group showed low nM inhibitory activities against wild-type HIV-1 protease. Selected compounds were further evaluated for their inhibitory activities against a panel of multidrug-resistant protease variants and for their antiviral potencies in MT-4 cells. The crystal structures of lopinavir (LPV) and two new inhibitors containing phenyloxazolidinone-based ligands in complex with wild-type HIV-1 protease have been determined A comparison of the inhibitor-protease structures with the LPV-protease structure provides valuable insight into the binding mode of the new inhibitors to the protease enzyme. Based on the crystal structures and knowledge of structure-activity relationships, new inhibitors can be designed with enhanced enzyme inhibitory and antiviral potencies.

Journal of Medicinal Chemistry published new progress about AIDS (disease). 192725-50-1 belongs to class pyrimidines, name is (S)-3-Methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoic acid, and the molecular formula is C9H16N2O3, Recommanded Product: (S)-3-Methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoic acid.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Flosi, William J. published the artcileDiscovery of imidazolidine-2,4-dione-linked HIV protease inhibitors with activity against lopinavir-resistant mutant HIV, Category: pyrimidines, the main research area is imidazolidinedione lopinavir analog preparation HIV protease inhibitor SAR.

A new series of HIV protease inhibitors has been designed and synthesized based on the combination of the (R)-(hydroxyethylamino)sulfonamide isostere and the cyclic urea component of lopinavir. The series was optimized by replacing the 6-membered cyclic urea linker with an imidazolidine-2,4-dione which readily underwent N-alkylation to incorporate various methylene-linked heterocycle groups that bind favorably in site 3 of HIV protease. Significant improvements compared to lopinavir were seen in cell culture activity vs. wild-type virus (pNL4-3) and the lopinavir-resistant mutant virus A17 (generated by in vitro serial passage of HIV-1 (pNL4-3) in MT-4 cells). Select imidazolidine-2,4-dione containing PIs were also more effective at inhibiting highly resistant patient isolates Pt1 and Pt2 than lopinavir. Pharmacokinetic data collected for compounds in this series varied considerably when coadministered orally in the rat with an equal amount of ritonavir (5 mg/kg each). The AUC values ranged from 0.144 to 12.33 μg h/mL.

Bioorganic & Medicinal Chemistry published new progress about AIDS (disease). 192725-50-1 belongs to class pyrimidines, name is (S)-3-Methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)butanoic acid, and the molecular formula is C9H16N2O3, Category: pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Humphrey, Guy R. published the artcileDevelopment of a Second-Generation, Highly Efficient Manufacturing Route for the HIV Integrase Inhibitor Raltegravir Potassium, HPLC of Formula: 519028-33-2, the main research area is Raltegravir Potassium preparation scaleup methylation amidoxime rearrangement green chem.

A manufacturing route for the synthesis of Raltegravir Potassium was developed via thermal rearrangement of amidoxime DMAD adducts to construct the key, highly functionalized hydroxypyrimidinone core, 2-(1-benzyloxycarbonylamino-1-methylethyl)-5,6-dihydroxypyrimidine-4-carboxylic acid Me ester. Utilizing this route, Raltegravir Potassium was prepared in nine linear chem. steps with 22% overall yield. A second-generation synthesis was subsequently developed that solved the key chem., productivity, and environmental impact issues of the initial synthesis. Highlights of the new synthesis include a highly selective methylation, 3-4-fold higher productivity, and a 65% reduction of combined organic and aqueous waste produced. The efficient second-generation manufacturing route provides Raltegravir Potassium in 35% overall yield.

Organic Process Research & Development published new progress about Green chemistry. 519028-33-2 belongs to class pyrimidines, name is Benzyl (2-(4-((4-fluorobenzyl)carbamoyl)-5-hydroxy-6-oxo-1,6-dihydropyrimidin-2-yl)propan-2-yl)carbamate, and the molecular formula is C23H23FN4O5, HPLC of Formula: 519028-33-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Iltzsch, Max H. published the artcileStructure-activity relationship of nucleobase ligands of uridine phosphorylase from Toxoplasma gondii, HPLC of Formula: 19030-75-2, the main research area is pyrimidine base Toxoplasma uridine phosphorylase inhibition; structure uracil analog uridine phosphorylase inhibition.

Seventy-nine nucleobase analogs were evaluated as potential inhibitors of T. gondii uridine phosphorylase (UrdPase), and the apparent Ki (appKi) values for these compounds were determined Based on the inhibition data, a structure-activity relationship for the binding of nucleobase analogs to the enzyme was formulated, using uracil as a reference compound Two compounds were identified as very potent inhibitors of T. gondii UrdPase: 5-benzyloxybenzylbarbituric acid and 5-benzyloxybenzyluracil, which had appKi values of 0.32 and 2.5 μM, resp. A comparison of the results from the present study with those from similar studies on mammalian UrdPase and thymidine phosphorylase (dThdPase) revealed that there are both similarities and differences between the catalytic site of T. gondii UrdPase and the catalytic sites of the mammalian enzymes with respect to binding of uracil analogs. One compound, 6-benzyl-2-thiouracil, was identified as a potent, specific inhibitor (appKi = 14 μM) of T. gondii UrdPase, relative to mammalian UrdPase and dThdPase.

Biochemical Pharmacology published new progress about Enzyme kinetics. 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, HPLC of Formula: 19030-75-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia