Category: pyrimidines

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

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

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

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

Sturala, Jiri published the artcileElectron-Deficient Heteroarenium Salts: An Organocatalytic Tool for Activation of Hydrogen Peroxide in Oxidations, SDS of cas: 42839-08-7, the main research area is heteroarenium salt organocatalytic activation hydrogen peroxide oxidations.

A series of monosubstituted pyrimidinium and pyrazinium triflates and 3,5-disubstituted pyridinium triflates were prepared and tested as simple catalysts of oxidations with hydrogen peroxide, using sulfoxidation as a model reaction. Their catalytic efficiency strongly depends on the type of substituent and is remarkable for derivatives with an electron-withdrawing group, showing reactivity comparable to that of flavinium salts which are the prominent organocatalysts for oxygenations. Because of their high stability and good accessibility, 4-(trifluoromethyl)pyrimidinium and 3,5-dinitropyridinium triflates are the catalysts of choice and were shown to catalyze oxidation of aliphatic and aromatic sulfides to sulfoxides, giving quant. conversions, high preparative yields and excellent chemoselectivity. The high efficiency of electron-poor heteroarenium salts is rationalized by their ability to readily form adducts with nucleophiles, as documented by low pKR+ values (pKR+ < 5) and less neg. reduction potentials (Ered > -0.5 V). Hydrogen peroxide adducts formed in situ during catalytic oxidation act as substrate oxidizing agents. The Gibbs free energies of oxygen transfer from these heterocyclic hydroperoxides to thioanisole, obtained by calculations at the B3LYP/6-311++g(d,p) level, showed that they are much stronger oxidizing agents than alkyl hydroperoxides and in some cases are almost comparable to derivatives of flavin hydroperoxide acting as oxidizing agents in monooxygenases.

Journal of Organic Chemistry published new progress about Activation energy. 42839-08-7 belongs to class pyrimidines, name is Ethyl pyrimidine-2-carboxylate, and the molecular formula is C7H8N2O2, SDS of cas: 42839-08-7.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Henriksen, Ulla published the artcileFacile synthesis of N-(1-alkenyl) derivatives of 2,4-pyrimidinediones, Application In Synthesis of 19030-75-2, the main research area is pyrimidinedione alkenyl derivative synthesis.

N-(1-alkenyl) derivatives of 2,4-pyrimidinediones were prepared in a one pot synthesis from aldehydes and the nucleobases using trimethylsilyl trifluoromethanesulfonate (TfOTMS) as coupling reagent. Presilylation of the above nucleobases, and N6-benzoyladenine, with excess N,O-bis(trimethylsilyl)acetamide (BSA) followed by addition of one mol eq. TfOTMS yielded the N-(1-trimethylsilyloxyalkyl) derivatives

Nucleosides, Nucleotides & Nucleic Acids published new progress about Coupling reaction. 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, Application In Synthesis of 19030-75-2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sandosham, Jessie published the artcileSyntheses of 5-alkenylpyrimidines by organotin reactions, HPLC of Formula: 84755-30-6, the main research area is stannylpyrimidine preparation coupling alkenyl bromide; vinylpyrimidine; alkenylpyrimidine; halopyrimidine coupling vinyltin; pyrimidine alkenyl.

5-Stannylpyrimidine I (R = SnBu3) (II) was prepared from I (R = Br) by lithiation at -95° and quenching with Bu3SnCl. II is used in Pd-catalyzed coupling reactions with vinyl bromides to give 5-vinylpyrimidines I (R = CH:CHR1, R1 = H, Me, Ph). The opposite reaction sequence, i.e. Pd-catalyzed coupling between 5-halopyrimidines and vinyltin derivatives, is also described. Alternatively, the 5-vinylpyrimidines have been obtained by dehydrohalogenation with CsF and by a modified Wittig reaction. 2-Methylthiopyrimidines are transformed into the 2-methoxy derivatives or 2-pyrimidinones using chloramine-T in a simple one-pot synthesis.

Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry published new progress about Coupling reaction. 84755-30-6 belongs to class pyrimidines, name is 4-Methyl-2-(methylthio)pyrimidine-5-carbaldehyde, and the molecular formula is C7H8N2OS, HPLC of Formula: 84755-30-6.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Knoblauch, Bernd H. A. published the artcile5-substituted UTP derivatives as P2Y2 receptor agonists, Product Details of C7H10N2O2, the main research area is UTP analog preparation phosphorylation structure activity; uracil nucleotide crystal structure; purinergic P2Y2 receptor antagonist uracil nucleotide.

A series of 5-alkyl-substituted UTP derivatives, which had been synthesized previously with a moderate degree of purity, was resynthesized, purified, and characterized. Synthetic and purification procedures were optimized. New spectroscopic data, including 13C- and 31P NMR data, are presented. Phosphorylation reactions yielded a number of side products, such as the 2′-, 3′-, and 5′-monophosphates, the 2′,3′-cyclic monophosphates, and the 2′,3′-cyclic phosphates of the 5′-triphosphates. Furthermore, raw products were contaminated with inorganic phosphates, including cyclometatriphosphate, phosphate, and pyrophosphate. The uracil nucleotides were investigated for their potency to increase intracellular calcium concentrations by stimulation of P2Y2 receptors (P2Y2R) on NG108-15 cells, a mouse neuroblastoma × glioma cell line, and in human basal epithelial airway cells, including a cystic fibrosis (CF/T43) cell line. UTP exhibited EC50 values of ca. 1 μM (in NG108-15 cells) and of 0.1 μM (in CF/T43 cells), resp. 5-Substituted UTP derivatives were agonists at the P2Y2R, but were less potent than UTP. 5-Ethyl-UTP, for example, exhibited an EC50 value of 99 μM at P2Y2R of NG108-15 cells and proved to be a full agonist. With increasing volume of the 5-substituent of UTP derivatives, P2Y2 activity decreased.

European Journal of Medicinal Chemistry published new progress about Crystal structure. 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, Product Details of C7H10N2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sharma, Lalit Kumar published the artcileLipE guided discovery of isopropylphenyl pyridazines as pantothenate kinase modulators, Related Products of pyrimidines, the main research area is isopropylphenyl pyridazine derivative panthothenate kinase lipophilic ligand efficiency; Hit-to-lead; Lipophilic ligand efficiency; Pantothenate Kinase; Pyridazine.

Pantothenate kinase (PANK) is the critical regulator of intracellular levels of CoA and has emerged as an attractive target for treating neurol. and metabolic disorders. This report describes the optimization, synthesis, and full structure-activity relationships of a new chem. series of pantothenate competitive PANK inhibitors. Potent drug-like mols. were obtained by optimizing a high throughput screening hit, using lipophilic ligand efficiency (LipE) derived from human PANK3 IC50 values to guide ligand development. X-ray crystal structures of PANK3 with index inhibitors from the optimization were determined to rationalize the emerging structure activity relationships. The anal. revealed a key bidentate hydrogen bonding interaction between pyridazine and R306′ as a major contributor to the LipE gain observed in the optimization. A tractable series of PANK3 modulators with nanomolar potency, excellent LipE values, desirable physicochem. properties, and a well-defined structural binding mode was produced from this study.

Bioorganic & Medicinal Chemistry published new progress about Crystal structure. 38275-56-8 belongs to class pyrimidines, name is 5-Chloropyrimidine-2-carbonitrile, and the molecular formula is C5H2ClN3, Related Products of pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Gardner, Evan J. published the artcileTris(pyrazolyl)borate Copper Hydroxide Complexes Featuring Tunable Intramolecular H-Bonding, Recommanded Product: Ethyl pyrimidine-2-carboxylate, the main research area is crystal structure copper pyrazolylborate pendant heterocycle arm; copper pyridyl pyrimidyl pyrazolylborate preparation intramol hydrogen bonding.

A modular synthesis provides access to new tris(pyrazolyl)borate ligands XpyMeTpK that possess a single functionalized pendant pyridyl (py) or pyrimidyl (pyd) arm designed to engage in tunable intramol. H-bonding to metal-bound functionalities. To illustrate such H-bonding interactions, [XpyMeTpCu]2(μ-OH)2 (6a-6e) complexes were synthesized from the corresponding XpyMeTpCu-OAc (5a-5e) complexes. Single crystal x-ray structures of three new dinuclear [XpyMeTpCu]2(μ-OH)2 complexes reveal H-bonding between the pendant heterocycle and bridging hydroxide ligands while the donor arm engages the Cu center in an unusual monomeric DMAPMeTpCu-OH complex. Vibrational studies (IR) of each bridging hydroxide complex reveal reduced νOH frequencies that tracks with the H-bond accepting ability of the pendant arm. Reversible protonation studies that interconvert [XpyMeTpCu]2(μ-OH)2 and [XpyMeTpCu(OH2)]OTf species indicate that the acidity of the corresponding aquo ligand decreases with increasing H-bond accepting ability of the pendant arm.

Inorganic Chemistry published new progress about Crystal structure. 42839-08-7 belongs to class pyrimidines, name is Ethyl pyrimidine-2-carboxylate, and the molecular formula is C7H8N2O2, Recommanded Product: Ethyl pyrimidine-2-carboxylate.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia