Day: November 16, 2022

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

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

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

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

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