Day: November 16, 2022

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

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

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

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

Muraoka, Masako published the artcileAlkylated pyrimidine derivatives as antiviral agents. I. Syntheses and antiviral screening of alkylpyrimidine and 5-alkyluracil nucleoside, Recommanded Product: 5-N-Propyluracil, the main research area is glucopyranosyl uracils antiviral; antiviral glucopyranosyl uracils; uracils glucopyranosyl antiviral; ribofuranosyl uracils antiviral.

5-Al-kyluracil, 3-alkyluracil, 5-alkylisocytosine, 5-alkyl-6-methylisocytosine, 3-alkyl-6-methyluracil, 1-(β-D-glucopyranosyl)-5-alkyluracil and 1-(β-D-ribofuranosyl)-5-alkyluracil were prepared and screened for antivirial activity on both RNA- and DNA-containing viruses. For RNA virus, type I Mahoney polio virus, and K-2211 strain ECHO-28 virus were used. For DNA viruses, type-I and type-12 strains adeno virus and DV 96 strain vaccinia virus were used. 5-Butyluracil and 1-(β-D-ribofuranosyl)-5-butyluracil (I) were effective against both RNA and DNA viruses. I was the more effective and exerted a broader spectrum than 5-fluorodeoxyuridine.

Chemical & Pharmaceutical Bulletin 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

Easmon, J. published the artcileThiazolyl and benzothiazolyl hydrazones derived from α-(N)-acetylpyridines and diazines: synthesis, antiproliferative activity and CoMFA studies, SDS of cas: 67073-96-5, the main research area is thiazolyl hydrazone preparation antiproliferative cancer CoMFA; QSAR thiazolyl hydrazone antiproliferative cancer; benzothiazolyl hydrazone antiproliferative cancer CoMFA.

The synthesis of a series of thiazolyl and benzothiazolyl hydrazones derived from α-(N)-acylpyridines, -quinolines, -isoquinolines, -pyridazines, -pyrimidines, and -pyrazines is reported. The stereochem. of these compounds was determined by NMR spectroscopic methods. The antiproliferative activity of the novel compounds was quantified in tissue culture (melanoma, breast carcinoma, colon adenocarcinoma, epitheloid cervix carcinoma, Burkitt’s lymphoma, leukemia, and hydroxyurea sensitive and resistant myelogenous leukemia sublines). All compounds exhibited profound antiproliferative activity, in particular against Burkitt’s lymphoma cells. Out of this series, some were 13-900 times more potent than hydroxyurea and no cross-resistance to hydroxyurea was observed A predictive 3D-QSAR model using the CoMFA approach was established.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 67073-96-5 belongs to class pyrimidines, name is 1-(6-Methylpyrimidin-4-yl)ethanone, and the molecular formula is C7H8N2O, SDS of cas: 67073-96-5.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Burger, Matthew T. published the artcileSynthesis and in Vitro and in Vivo Evaluation of Phosphoinositide-3-kinase Inhibitors, Product Details of C4HBr3N2, the main research area is morpholino heterocyclic pyrimidine preparation phosphoinositide kinase inhibitor; PI3K/AKT pathway; phosphoinositide 3-kinase alpha.

Phosphoinositide-3-kinases (PI3K) are important oncol. targets due to the deregulation of this signaling pathway in a wide variety of human cancers. A series of 2-morpholino, 4-substituted, 6-(3-hydroxyphenyl) pyrimidines have been reported as potent inhibitors of PI3Ks. Herein, we describe the structure-guided optimization of these pyrimidines with a focus on replacing the phenol moiety, while maintaining potent target inhibition and improving in vivo properties. A series of 2-morpholino, 4-substituted, 6-heterocyclic pyrimidines, which potently inhibit PI3K, were discovered. Within this series a compound (I) was identified with suitable pharmacokinetic (PK) properties, which allowed for the establishment of a PI3K PK/pharmacodynamic-efficacy relationship as determined by in vivo inhibition of AKTSer473 phosphorylation and tumor growth inhibition in a mouse A2780 tumor xenograft model.

ACS Medicinal Chemistry Letters published new progress about Antitumor agents. 36847-11-7 belongs to class pyrimidines, name is 2,4,6-Tribromopyrimidine, and the molecular formula is C4HBr3N2, Product Details of C4HBr3N2.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Axten, Jeffrey M. published the artcileDiscovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acetyl}-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (GSK2606414), a potent and selective first-in-class inhibitor of protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), COA of Formula: C7H5BrClN3, the main research area is methyltrifluoromethylphenylacetyldihydroindolylpyrrolopyrimidinamine preparation SAR PERK inhibitory antitumor.

Protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is activated in response to a variety of endoplasmic reticulum stresses implicated in numerous disease states. Evidence that PERK is implicated in tumorigenesis and cancer cell survival stimulated our search for small mol. inhibitors. Through screening and lead optimization using the human PERK crystal structure, we discovered compound I (GSK2606414), an orally available, potent, and selective PERK inhibitor. Compound I inhibits PERK activation in cells and inhibits the growth of a human tumor xenograft in mice.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 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, COA of Formula: C7H5BrClN3.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Horiuchi, Takao published the artcileDiscovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: Synthesis, biological evaluation and structure-activity relationships. Part 2, Recommanded Product: Thieno[2,3-d]pyrimidine, 4-chloro-6-(1,1-dimethylethyl)-, the main research area is cyclin dependent kinase 4 CDK4 inhibitor cancer; hydrazone derivative SAR preparation.

The design, synthesis and evaluation of novel thieno[2,3-d]pyrimidin-4-yl hydrazone analogs as cyclin-dependent kinase 4 (CDK4) inhibitor are described. Focusing on the optimization of the heteroaryl moiety at the hydrazone with substituted Ph groups, 4-[(methylamino)methyl]benzaldehyde (22)(I) and 5-isoindolinecarbaldehyde (24)(II) (6-tert-butylthieno[2,3-d]pyrimidin-4-yl)hydrazone derivatives have been identified. In this paper, the potency, selectivity profile and structure-activity relationships of our synthetic compounds are discussed.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 439692-55-4 belongs to class pyrimidines, name is Thieno[2,3-d]pyrimidine, 4-chloro-6-(1,1-dimethylethyl)-, and the molecular formula is C10H11ClN2S, Recommanded Product: Thieno[2,3-d]pyrimidine, 4-chloro-6-(1,1-dimethylethyl)-.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia

Lefranc, Julien published the artcileDiscovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor, SDS of cas: 3122-84-7, the main research area is BAY985 TBK1 IKK epsilon inhibitor antitumor activity antiproliferative melanoma.

The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homolog IKKε are noncanonical members of the inhibitor of the nuclear factor κB (IκB) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKKε inhibitor BAY-985. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 and displays antiproliferative efficacy in the melanoma cell line SK-MEL-2 but showed only weak antitumor activity in the SK-MEL-2 human melanoma xenograft model.

Journal of Medicinal Chemistry published new progress about Antitumor agents. 3122-84-7 belongs to class pyrimidines, name is 4-Chloro-6-(methoxymethyl)pyrimidine, and the molecular formula is C6H7ClN2O, SDS of cas: 3122-84-7.

Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia