Category: pyrimidines

Nakayama, Chikao published the artcileSynthetic nucleosides and nucleotides. XII. Synthesis and antiviral activities of several 1-β-D-arabinofuranosyl-5-alkyluracils and their 5′-monophosphates, HPLC of Formula: 19030-75-2, the main research area is arabinofuranosylalkyluracil preparation virucide; nucleoside arabinofuranosylalkyluracil; nucleotide arabinofuranosylalkyluracil; uracil arabinofuranosylalkyl.

Arabinofuranosyluracils I (R = Me, Et, Pr, Bu) were prepared by acid hydrolysis of anhydronucleosides II. II were prepared from pyrimidines III by 2 routes : (a) condensation with 1,2-di-O-acetyl-3-O-p-toluenesulfonyl-5-O-benzoyl-D-xylofuranose and treatment of the products with MeONa-MeOH; (b) condensation with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose followed by debenzoylation and cyclization. Phosphorylation of I (R = Me, Et) or II (R = Me, Et) with tetrachloropyrophosphate in MeCn followed by treatment with acid gave 1-β-D-arabinofuranosyl-5-alkyluracil 5′-phosphates (IV). Antiviral activities of I, II, and IV against herpes simplex 1 and 2 are given; I (R = Me) and IV (R = Me) were significantly active against both the viruses.

Journal of Carbohydrates, Nucleosides, Nucleotides published new progress about Antiviral agents. 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

Kulikowski, Tadeusz published the artcile5-Substituted arabinofuranosyluracil nucleosides: synthesis and antiviral properties, Recommanded Product: 5-N-Propyluracil, the main research area is arabinofuranosyluracil nucleoside preparation virucide; alkyluracil arabinofuranosyl; structure antiviral activity arabinofuranosyluracil.

The title nucleosides I (R = Et, Pr, Me2CH, Bu), their α-anomers and N-3 isomers were prepared by a number of different procedures based on the catalytic condensation of the corresponding 5-alkyl-2,4-bis(trimethylsilyloxy)pyrimidines with 2,3,5-tri-O-benzyl-α-D-arabinofuranosyl chloride. The resulting protected nucleosides were deblocked by a new procedure based on the use of BF3.Et2O and EtSH. The chloromercuri derivative of ara-U (I; R = H) on reaction with allyl chloride in the presence of Li2PdCl4 gave I (R = allyl), which on catalytic hydrogenation gave I (R = Pr). The antiviral activities of these compounds were evaluated. I (R = allyl) showed moderate specific activity against herpes simplex type 1 virus in PRK cell culture. Structure-activity relationships are discussed.

Acta Biochimica Polonica published new progress about Antiviral agents. 19030-75-2 belongs to class pyrimidines, name is 5-N-Propyluracil, and the molecular formula is C7H10N2O2, Recommanded Product: 5-N-Propyluracil.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Sinha, Sarmistha published the artcileElectrophilicity of Pyridazine-3-carbonitrile, Pyrimidine-2-carbonitrile, and Pyridine-carbonitrile Derivatives: A Chemical Model To Describe the Formation of Thiazoline Derivatives in Human Liver Microsomes, Computed Properties of 38275-56-8, the main research area is electrophilicity model pyridazine pyrimidine pyridine carbonitrile cysteine adduct; thiazoline liver microsome glutathione acetylcysteine cysteine protease inhibitor.

Certain aromatic nitriles are well-known inhibitors of cysteine proteases. The mode of action of these compounds involves the formation of a reversible or irreversible covalent bond between the nitrile and a thiol group in the active site of the enzyme. However, the reactivity of these aromatic nitrile-substituted heterocycles may lead inadvertently to nonspecific interactions with DNA, protein, glutathione, and other endogenous components, resulting in toxicity and complicating the use of these compounds as therapeutic agents. In the present study, the intrinsic reactivity and associated structure-property relationships of cathepsin K inhibitors featuring substituted pyridazines [6-phenylpyridazine-3-carbonitrile, 6-(4-fluorophenyl)pyridazine-3-carbonitrile, 6-(4-methoxyphenyl)pyridazine-3-carbonitrile, 6-p-tolylpyridazine-3-carbonitrile], pyrimidines [5-p-tolylpyrimidine-2-carbonitrile, 5-(4-fluorophenyl)pyrimidine-2-carbonitrile], and pyridines [5-p-tolylpicolinonitrile and 5-(4-fluorophenyl)picolinonitrile] were evaluated using a combination of computational and anal. approaches to establish correlations between electrophilicity and levels of metabolites that were formed in glutathione- and N-acetylcysteine-supplemented human liver microsomes. Metabolites that were characterized in this study featured substituted thiazolines that were formed following rearrangements of transient glutathione and N-acetylcysteine conjugates. Peptidases including γ-glutamyltranspeptidase were shown to catalyze the formation of these products, which were formed to lesser extents in the presence of the selective γ-glutamyltranspeptidase inhibitor acivicin and the nonspecific peptidase inhibitors phenylmethylsulfonyl fluoride and aprotinin. Of the chem. series mentioned above, the pyrimidine series was the most susceptible to metabolism to thiazoline-containing products, followed, in order, by the pyridazine and pyridine series. This trend was in keeping with the diminishing electrophilicity across these series, as demonstrated by in silico modeling. Hence, mechanistic insights gained from this study could be used to assist a medicinal chem. campaign to design cysteine protease inhibitors that were less prone to the formation of covalent adducts.

Chemical Research in Toxicology published new progress about Electrophilicity. 38275-56-8 belongs to class pyrimidines, name is 5-Chloropyrimidine-2-carbonitrile, and the molecular formula is C5H2ClN3, Computed Properties of 38275-56-8.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Stoner, Eric J. published the artcileSynthesis of ABT-378, an HIV Protease Inhibitor Candidate: Avoiding the Use of Carbodiimides in a Difficult Peptide Coupling, Formula: C9H16N2O3, the main research area is peptide coupling acyl imidazolide protease inhibitor ABT 378 preparation.

An alternative to carbodiimide-mediated peptide coupling protocols has been developed for carboxylic acid I (R = OH) prone to decomposition by polymerization This method, involving the in situ generation of acyl imidazolide I (R = imidazolyl) from acid chloride I (R = Cl), has been applied to the preparation of a lead clin. HIV protease inhibitor candidate, ABT-378 (II). The nature of the polymerization and optimization of the new reaction conditions are presented.

Organic Process Research & Development published new progress about Peptide coupling. 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, Formula: C9H16N2O3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Gadhachanda, Venkat R. published the artcile4-Aminopyrimidines as novel HIV-1 inhibitors, Application of 4-Chloro-6-(methoxymethyl)pyrimidine, the main research area is aminopyrimidine preparation HIV1 inhibitor SAR.

A series of 4-aminopyrimidines was identified as novel HIV inhibitors of unknown mol. target. Structural modifications were carried out to establish SAR and identify the linking site for target identification. A number of analogs were found to possess single digit inhibitory activity for HIV replication. Several analogs with various potential linkers, including a biotinated analog, also exhibited excellent potency, and could serve as tools for the identification of novel anti-HIV targets.

Bioorganic & Medicinal Chemistry Letters published new progress about Anti-HIV agents. 3122-84-7 belongs to class pyrimidines, name is 4-Chloro-6-(methoxymethyl)pyrimidine, and the molecular formula is C6H7ClN2O, Application of 4-Chloro-6-(methoxymethyl)pyrimidine.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Kawasuji, Takashi published the artcileA platform for designing HIV integrase inhibitors. 2-Hydroxy-3-heteroaryl acrylic acid derivatives as novel HIV integrase inhibitor and modeling of hydrophilic and hydrophobic pharmacophores, Formula: C7H8N2O2, the main research area is hydroxyheteroaryl acrylic acid derivative preparation HIV1 integrase inhibitor antiaids.

The authors present a novel series of HIV integrase inhibitors, showing IC50s ranging from 0.01 to over 370 μM in an enzymic assay. Furthermore, pharmacophore modeling study for the inhibitors was carried out to elucidate the structure-activity relationships. Finally, the authors found a 3D-pharmacophore model, which is composed of a hydrophilic and a hydrophobic domain, providing valuable information for designing other novel types of integrase inhibitors.

Bioorganic & Medicinal Chemistry published new progress about Anti-HIV agents. 42839-08-7 belongs to class pyrimidines, name is Ethyl pyrimidine-2-carboxylate, and the molecular formula is C7H8N2O2, Formula: C7H8N2O2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Ku, Therese published the artcileSynthesis of distal and proximal fleximer base analogues and evaluation in the nucleocapsid protein of HIV-1, Related Products of pyrimidines, the main research area is fleximer bipyrimidine synthesis antiHIV HIV1 nucleocapsid protein; Fleximers; HIV-1; NC; Pyrimidine; Synthesis.

Anti-HIV-1 drug design has been notably challenging due to the virus’ ability to mutate and develop immunity against com. available drugs. The aims of this project were to develop a series of fleximer base analogs that not only possess inherent flexibility that can remain active when faced with binding site mutations, but also target a non-canonical, highly conserved target: the nucleocapsid protein of HIV (NC). The compounds were predicted by computational studies not to function via zinc ejection, which would endow them with significant advantages over non-specific and thus toxic zinc-ejectors. The target fleximer bases were synthesized using palladium-catalyzed cross-coupling techniques and subsequently tested against NC and HIV-1. The results of those studies are described herein.

Bioorganic & Medicinal Chemistry published new progress about Anti-HIV agents. 36847-11-7 belongs to class pyrimidines, name is 2,4,6-Tribromopyrimidine, and the molecular formula is C4HBr3N2, Related Products of pyrimidines.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Herstad, Gunnar published the artcileDecarboxylation in the synthesis of 4-alkyl-, 4-alkenyl- and 4-acylpyrimidines, Product Details of C5H5ClN2S, the main research area is pyrimidine alkyl alkenyl acyl preparation decarboxylation carboxypyrimidine; microwave irradiation decarboxylation pyrimidine preparation.

Decarboxylation of allylic esters I (R = H, Me, n = 0; R = Me, n = 2) of 4-carboxypyrimidines in toluene at 111 °C in the presence of a Pd(0) catalyst, tetrakis(triphenylphosphine) palladium, gives a mixture of a 4-alkenylpyrimidine II and a pyrimidine unsubstituted in the 4-position. If the decarboxylation is carried out in the presence of benzaldehyde, then benzaldehyde is added to the 4-position. Decarboxylation of 4-carboxypyrimidines I in the presence of different electrophiles, benzaldehyde, acetophenone and benzoyl chloride, results in incorporation of the electrophile into the 4-position, III [R = CH(OH)Ph, CMe(Ph)(OH), COPh, X = Cl; R = CH(OH)Ph, X = Br], together with a pyrimidine unsubstituted in the 4-position. Use of microwave irradiation enhances the rate of the decarboxylations.

Journal of Heterocyclic Chemistry published new progress about Decarboxylation. 38275-42-2 belongs to class pyrimidines, name is 5-Chloro-2-(methylthio)pyrimidine, and the molecular formula is C5H5ClN2S, Product Details of C5H5ClN2S.

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

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