Month: November 2022

Meegalla, Sanath K. published the artcileSynthesis and GABA receptor potency of 3-thiomethyl-4-(hetero)aryl-5-amino-1-phenylpyrazoles, Computed Properties of 762263-64-9, the publication is Bioorganic & Medicinal Chemistry Letters (2004), 14(19), 4949-4953, database is CAplus and MEDLINE.

A convenient synthetic route to 4-arylpyrazoles, e.g., I, is described. The potential for insecticidal activity through GABA channel blockage by this series of compounds, as well as their selectivity for insect vs. mammalian receptors, were explored through in vitro and in vivo assays.

Bioorganic & Medicinal Chemistry Letters published new progress about 762263-64-9. 762263-64-9 belongs to pyrazines, auxiliary class Pyrazine,Boronic acid and ester,Boronic Acids, name is Pyrazin-2-ylboronic acid, and the molecular formula is C4H5BN2O2, Computed Properties of 762263-64-9.

Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem

Krinkova, Jana published the artcileIn vitro antifungal activity of 5-alkyl-6-chloropyrazine-2-carboxamides and the corresponding thioamides, Product Details of C5H5N3S, the publication is Folia Pharmaceutica Universitatis Carolinae (2001), 21-26, database is CAplus.

Homolytic alkylation of 6-chloropyrazine-2-carbonitrile by alkanoic acids and subsequent partial hydrolysis afforded 5-alkyl-6-chloropyrazine-2-carboxamides, which were converted by Lawesson’s reagent into corresponding thioamides. Products were tested for their in vitro antifungal activity. The structure-activity relationships were studied. Three of the tested compounds, 6-chloro-5-butylpyrazine-2-carbothioamide, 6-chloro-5-isobutylpyrazine-2-carbothioamide, and 6-chloro-5-(1,1-dimethylethyl)-pyrazine-2-carbothioamide, were active in vitro against all 8 strains tested (MIC values ranged from 62.5 to 500 μmol.dm^-3). Thioamides exerted higher antifungal activity than the corresponding amides. The values of hydrophobicity in the series of studied compounds were determined The activity dropped or disappeared at the compounds with lower lipophilicity (log P > 2.28). Some interesting correlation between antimycobacterial and antifungal activity was found.

Folia Pharmaceutica Universitatis Carolinae published new progress about 4604-72-2. 4604-72-2 belongs to pyrazines, auxiliary class Pyrazine,Amine,Amide, name is Pyrazine-2-carbothioamide, and the molecular formula is C5H5N3S, Product Details of C5H5N3S.

Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem

Garamvolgyi, Rita published the artcileDesign and synthesis of new imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrazine derivatives with antiproliferative activity against melanoma cells, Application In Synthesis of 117718-92-0, the publication is European Journal of Medicinal Chemistry (2016), 623-643, database is CAplus and MEDLINE.

A new series of diarylamide and diarylurea derivatives containing imidazo[1,2-a]pyridine or imidazo[1,2-a]pyrazine scaffold I (R = H, 3,5-F, 3-CF₃, etc.), II, III was designed and synthesized to investigate their in vitro efficacy against the A375P human melanoma cell line. Several compounds expressing submicromolar IC₅₀ values against the A375P cells was observed, from which I (R = 3,5-F), II (R = 3,5-Cl), III (R = 3,5-Cl, 3,5-(CF₃)₂, 4-F-3-CF₃) demonstrated the highest potencies with IC₅₀ below 0.06 μM.

European Journal of Medicinal Chemistry published new progress about 117718-92-0. 117718-92-0 belongs to pyrazines, auxiliary class Other Aromatic Heterocyclic,Bromide,Amine, name is 3-Bromoimidazo[1,2-a]pyrazin-8-amine, and the molecular formula is C6H5BrN4, Application In Synthesis of 117718-92-0.

Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem

Dhumal, Sambhaji T. published the artcileSynthesis and Antitubercular activity of New Thiazolidinones with Pyrazinyl and Thiazolyl scaffolds, Category: pyrazines, the publication is Journal of Heterocyclic Chemistry (2017), 54(1), 125-130, database is CAplus.

Emergence of multidrug resistant and extensively drug resistant tuberculosis has prompted to develop new mol. entities to treat the disease. A series of new 4-thiazolidinones with pyrazinyl and thiazolyl scaffolds has been synthesized, and their antitubercular activity is reported. The title 4-thiazolidinones, N-(pyrazinyl substituted thiazoloylamino)-2-aryl-4-thiazolidinones I [ R = H, 4-Me, 2-F, etc] have been first time prepared using pyrazinamide as a starting material via five successive steps. The purity and the structures of the intermediates (carboethoxythiazole, acid hydrazide, and azomethines) and title thiazolidinones I [ R = H, 4-Me, 2-F, etc] have been confirmed by TLC and spectral analyses, resp. An antitubercular screening of the new 4-thiazolidinones has been performed on bacterial strains, Mycobacterium tuberculosis H37Ra and Mycobacterium BCG using the solutions of different concentrations of the compounds I [ R = H, 4-Me, 2-F, etc] and the screening results are presented. Compound I [ R = H] has displayed notable antitubercular activity.

Journal of Heterocyclic Chemistry published new progress about 4604-72-2. 4604-72-2 belongs to pyrazines, auxiliary class Pyrazine,Amine,Amide, name is Pyrazine-2-carbothioamide, and the molecular formula is C5H5N3S, Category: pyrazines.

Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem

Patinote, Cindy published the artcileImidazo[1,2-a]quinoxalines for melanoma treatment with original mechanism of action, Formula: C6H5BrN4, the publication is European Journal of Medicinal Chemistry (2021), 113031, database is CAplus and MEDLINE.

The malignant transformation of melanocytes causes several thousand deaths each year, making melanoma an important public health concern. Melanoma is the most aggressive skin cancer, which incidence has regularly increased over the past decades. We described here the preparation of new compounds based on the 1-(3,4-dihydroxyphenyl)imidazo[1,2-a]quinoxaline structure. Different positions of the quinoxaline moiety were screened to introduce novel substituents in order to study their influence on the biol. activity. Several alkylamino or alkyloxy groups were also considered to replace the methylamine of our first generation of Imiqualines. Imidazo[1,2-a]pyrazine derivatives were also designed as potential minimal structure. The investigation on A375 melanoma cells displayed interesting in vitro low nanomolar cytotoxic activity. Among them, 9d (EAPB02303) is particularly remarkable since it is 20 times more potent than vemurafenib, the reference clin. therapy used on BRAF mutant melanoma. Contrary to the first generation, EAPB02303 does not inhibit tubulin polymerization, as confirmed by an in vitro assay and a mol. modelisation study. The mechanism of action for EAPB02303 highlighted by a transcriptomic anal. is clearly different from a panel of 12 well-known anticancer drugs. In vivo EAPB02303 treatment reduced tumor size and weight of the A375 human melanoma xenografts in a dose-dependent manner, correlated with a low mitotic index but not with necrosis.

European Journal of Medicinal Chemistry published new progress about 117718-92-0. 117718-92-0 belongs to pyrazines, auxiliary class Other Aromatic Heterocyclic,Bromide,Amine, name is 3-Bromoimidazo[1,2-a]pyrazin-8-amine, and the molecular formula is C6H5BrN4, Formula: C6H5BrN4.

Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem

Coutard, Bruno published the artcileAssessment of Dengue virus helicase and methyltransferase as targets for fragment-based drug discovery, Name: Thieno[2,3-b]pyrazin-7-amine, the publication is Antiviral Research (2014), 61-70, database is CAplus and MEDLINE.

Seasonal and pandemic flaviviruses continue to be leading global health concerns. With the view to help drug discovery against Dengue virus (DENV), a fragment-based exptl. approach was applied to identify small mol. ligands targeting two main components of the flavivirus replication complex: the NS3 helicase (Hel) and the NS5 mRNA methyltransferase (MTase) domains. A library of 500 drug-like fragments was first screened by thermal-shift assay (TSA) leading to the identification of 36 and 32 fragment hits binding Hel and MTase from DENV, resp. In a second stage, we set up a fragment-based X-ray crystallog. screening (FBS-X) in order to provide both validated fragment hits and structural binding information. No fragment hit was confirmed for DENV Hel. In contrast, a total of seven fragments were identified as DENV MTase binders and structures of MTase-fragment hit complexes were solved at resolution at least 2.0 Å or better. All fragment hits identified contain either a five- or six-membered aromatic ring or both, and three novel binding sites were located on the MTase. To further characterize the fragment hits identified by TSA and FBS-X, we performed enzymic assays to assess their inhibition effect on the N7- and 2′-O-MTase enzymic activities: five of these fragment hits inhibit at least one of the two activities with IC₅₀ ranging from 180 μM to 9 mM. This work validates the FBS-X strategy for identifying new anti-flaviviral hits targeting MTase, while Hel might not be an amenable target for fragment-based drug discovery (FBDD). This approach proved to be a fast and efficient screening method for FBDD target validation and discovery of starting hits for the development of higher affinity mols. that bind to novel allosteric sites.

Antiviral Research published new progress about 59944-75-1. 59944-75-1 belongs to pyrazines, auxiliary class Other Aromatic Heterocyclic,Amine, name is Thieno[2,3-b]pyrazin-7-amine, and the molecular formula is C6H5N3S, Name: Thieno[2,3-b]pyrazin-7-amine.

Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem

Kushner, S. published the artcileExperimental chemotherapy of tuberculosis. II. The synthesis of pyrazinamides and related compounds, Application In Synthesis of 4604-72-2, the publication is Journal of the American Chemical Society (1952), 3617-21, database is CAplus.

cf. C.A. 43, 5025b. To 5.0 g. 2-aminothiazole was added slowly a suspension of 3.5 g. freshly prepared pyrazinoyl chloride (I) in 15 cc. EtOAc, the mixture heated 10 min. on a steam bath, the supernatant hot EtOAc decanted, the residue heated again with 15 cc. EtOAc, the procedure repeated, the combined EtOAc-layers were evaporated to dryness, and the solid, yellow residue was washed with cold H₂O, filtered, dried, and recrystallized from hot EtOAc to give 3.0 g. (60%) N-(2-thiazolyl)pyrazinamide, m. 187-9°. By the same procedure were prepared the following N-mono- or N,N-disubstituted pyrazinamides (substituent given): Me, m. 105°; Me₂, m. 70-2°; Bu 20%, b₃ 167-70°; C₁₆H₃₃ 50%, m. 85-7° (from C₆H₆-EtOH); PhCH₂, m. 116-18°; Ph 55-60%, m. 127-30°; p-ClC₆H₄ 60%, m. 184-5°; o-ClC₆H₄ 60%, m. 135-6°; m-ClC₆H₄ 60%, m. 145-7°; 2-pyridyl, 65%, m. 138-40°; 3-pyridyl 62%, m. 185-6°; 1-piperidyl 80%, m. 68-9° (from Me₂CO); 3-quinoxalyl 76%, m. 205-6°; and 2-pyrazinyl 40%, m. 190-2°. Et N-pyrazinoyl-β-alanate (II) (1 g.) in 25 cc. MeOH saturated with NH₃ at 0° gave 55% β-(N’-pyrazinoylamino)propionamide, m. 206-8°. Me pyrazinoate (III) (5.0 g.), 7.5 g. HO(CH₂)₂NHCH₂CH₂NH₂, and 30 cc. absolute EtOH refluxed 60 hrs. gave 84% N-(2-hydroxyethyl)-N’-pyrazinoylethylene-diamine, m. 107-8°. Similarly were prepared from III and iso-BuNH₂, N-isobutylpyrazinamide, m. 63-4° (from C₆H₆-EtOH); and from III and p-MeOC₆H₄CH₂NH₂, 50% N-(p-methoxybenzyl)pyrazinamide m. 134-6°. By ammonolysis of the appropriate, substituted pyrazinoates were prepared the following substituted pyrazinamides (substituents given): 6-Me, 83%, m. 204-5° (from EtOH); 3-H₂N ,50%, m. 237-9°; 3-amino-6-bromo (IV) 80%, m. 215-17°; 3-HO, m. 265° (decomposition). 2,3-Pyrazinedicarboxamide (V) m. 240°, (decomposition); 2,6-isomer, 90%, m. 300° (decomposition); 6-Me derivative of IV, 80%, m. 215-17°. To 15 g. H₂N(CH₂)₂-CH:CHCO₂H and 5.2 g. NaOH in 100 cc. ice-cold H₂O were added simultaneously during 30 min. with stirring 9 g. NaOH in 50 cc. H₂O and 10 g. I in 50 cc. C₆H₆, the mixture was stirred 30 min. at room temperature, the C₆H₆ removed in vacuo, and the resulting aqueous solution acidified with 6N HCl to give 70% 5-pyrazinoylamino-2-pentenoic acid, m. 200-1°. By the same procedure but with NaHCO₃ were prepared 70% di-Et N-pyrazinoylaspartate, m. 64-5°, and 50% II, m. 87-9°. Cyanopyrazine (VI), b_6-7 86-7°, (21.9 g.) in 125 cc. dry Et₂O and 8.4 g. absolute MeOH saturated with HCl at 0° and the mixture let stand 15 hrs. at room temperature gave 25.6 g. Me pyrazinimidate-2HCl, m. above 150° (with darkening and decomposition); this was added to 600 cc. ice-cold 8% alc. NH₃, the mixture shaken 1 day at room temperature, filtered, the filtrate evaporated to dryness in vacuo, and the solid residue boiled briefly with 125 cc. Me₂CO, filtered, and crystallized from EtOH to give 6 g. pyrazinecarboxamidine-HCl, m. 215-18° (decomposition); picrate, m. 221-4°. VI (15 g.) in 200 cc. saturated, alc. NH₃ saturated with H₂S and the mixture let stand overnight at room temperature yielded 90% thiocarbamyl-pyrazine, m. 195-6°. To 13.8 g. III and 7 g. NH₂OH.HCl in 50 cc. ice-water was added 16 cc. 12.5 N NaOH, and the mixture let stand 15 min. in an ice bath and neutralized with HCl to give 72% pyrazinohydroxamic acid, m. 163-5° (from H₂O), gives a wine color with alc. FeCl₃. Pyrazinamide (VII) (21 g.), 84 cc. AcOH, and 210 cc. 30% H₂O₂ heated 34 hrs. at 56° gave 45% pyrazinoic acid 4-oxide, m. 292-3° (decomposition) (from AcOH), also obtained by similar oxidation of VI. VII (10 g.) and 17 g. MeI refluxed 12 hrs. in 100 cc. MeOH yielded 38% 3-carbamyl-1-methylpyrazinium iodide (VIII), m. 192-202° (from H₂O). VII (4 g.) refluxed 1.25 hrs. with 20 cc. Ac₂O gave 55% N-Ac derivative (IX), of VII, m. 92-7°. VII (15 g.), 18 cc. aqueous CH₂O, and 0.2 g. K₂CO₃ heated on a steam bath until a clear solution was formed yielded 80% N-(hydroxymethyl)pyrazinamide, m. 129-36.5°. 1-Phenylsulfonyl-2-pyrazinoylhydrazine (X) 86% was obtained from PhSO₂Cl and pyrazinoic acid hydrazide(XI),m. 169°. Dry X(10g.)and 18g. finely powd. Na₂CO₃ heated at 150-70° and 35 mm. pressure, and the vapors bubbled through 3% aqueous H₂NC(:S)NHNH₂ gave 9% pyrazinaldehyde thiosemicarbazone (XII), m. 237-9° (decomposition). XI (2.8 g.) and 3.3 g. p-AcNHC₆H₄CHO in 100 cc. absolute EtOH refluxed 5 min. yielded 92% pyrazinoic acid (p-acetamidobenzylidene)hydrazide, m. above 250°. To MeMgI (from 50 g. MeI and 9 g. Mg) in 300 cc. dry Et₂O was added dropwise over 20 min. 13 g. VI in 150 cc. Et₂O, and the mixture poured on ice and acidified to give 77% acetylpyrazine (XIII), m. 76-8° (from Et₂O); thiosemicarbazone (XIV), 67%, m. 226-7° (decomposition); oxime, 50%, m. 113-15° (sublimed at 100° and 0.05 mm.). Powd. S (1.5 g.) in 15 cc. concentrated NH₄OH saturated with H₂S, 3.0 g. XIII, and 12 cc. dioxane heated 24 hrs. in a sealed tube at 170° gave 0.2 g. pyrazinacetamide, m. 108-10° (from EtOH-petr. ether). XIII (12.2 g.), 5.2 g. S, and 15 cc. morpholine refluxed 6 hrs. yielded 80% 4-(2-pyrazinylthioacetyl)morpholine, m. 92-3°. HCl passed through 29.6 g. pyrazinyldiazomethyl ketone (XV) in 600 cc. dry Et₂O until the N evolution ceased gave 30% (chloroacetyl)pyrazine, m. 85-6°; thiosemicarbazone, 30%, m. 222-4°. To 30 cc. glacial AcOH was added at 50° in portions 6.4 g. XV, and, after all the N had been evolved, 0.5 g. KOAc, the mixture heated 1 hr. at 100°, and the AcOH distilled off in vacuo to yield 10% (acetoxyacetyl)pyrazine, m. 67-8°. VI (5.1 g.), 3.3 g. NaN₃, 10 cc. glacial AcOH and 15 cc. iso-PrOH autoclaved 5 days at 150° gave 30% 5-pyrazinyl-1H-tetrazole, m. 182-4°. Concentrated aqueous solutions of 2-aminopyrazine and KSCN mixed and acidified during 1 hr. with 1 molar equivalent HCl gave 80% 1-pyrazinyl-2-thiourea, m. 128°. PhONa (36 g.) and 36 g. chloropyrazine refluxed 13 hrs. yielded 72% Ph pyrazinyl ether, m. 50-2°. 3-Methyl-2-quinoxalincarboxaldehyde thiosemicarbazone (XVI), m. 251-2° (decomposition) was obtained in 30% yield by refluxing the components 2 hrs. in absolute EtOH. All above mentioned pyrazine derivatives were tested in a standardized mouse test for T. B. activity at the arbitrary level of 0.2% of diet (8 mg./day), with survival as a criterion. VII, m. 189-91°, was highly active, and IX and XII showed a slight activity. All others were inactive; IV, V, VIII, X, XI, XII, and XIV were also toxic. The following addnl. pyrazine derivatives (substituents and m.ps. given) were also tested and found inactive: CO₂H, 225-6°; C(OAc):NH.2HCl, 180°; CO₂-Me.HCl, 46°; 6,2-Me(HO₂C), 138-40°; 2,3-(HO₂C)₂, 179-82°; 2,3-CONHCO-, m. 245°; and 6,2,3-Me(HO₂C)₂, 43.4°. XVI, 2-chloro-3-quinoxalinecarboxamide (XVII), m. 207-9°, and its N-PhCH₂ derivative did not exhibit T.B. activity in the above test.

Journal of the American Chemical Society published new progress about 4604-72-2. 4604-72-2 belongs to pyrazines, auxiliary class Pyrazine,Amine,Amide, name is Pyrazine-2-carbothioamide, and the molecular formula is C5H5N3S, Application In Synthesis of 4604-72-2.

Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem

Domzalska, Marta published the artcileSensors to the Diagnostic Assessment of Anticancer and Antimicrobial Therapies Effectiveness by Drugs a with Pyrazine Scaffold, Name: Pyrazine-2-carbothioamide, the publication is Chemosensors (2022), 10(1), 24, database is CAplus.

Treatment with pyrazine derivatives-antituberculosis pyrazinamide (PZA), anticancer bortezomib (BZM), and antifungal pyrazine-2-amidoxime (PAOX) and pyrazine-2-thiocarboxamide (PTCA)-is associated with side effects, as observed in the case of other therapeutic drugs. To prevent the side effects of pyrazine derivatives, researchers are working to develop a universal method that will detect these compounds in body fluids. There is a lack of literature data about voltammetric measurements with poly-L-amino acid-modified GCEs surfaces. The available reports describe the application of various modifications of these electrodes for the detection of different active substances of drugs; however, they do not indicate one particular method for the detection of drugs with a pyrazine skeleton. This research aimed to prepare three types of glassy carbon electrodes (GCEs) with modified surfaces by electropolymerization using 1, 10, and 100 mM solutions of L-glycine (Gly), L-alanine (Ala), L-lysine (Lys), resp. The poly-amino acid coatings applied on GCE surfaces were analyzed in detail under a three-dimensional (3D) microscope and were used as chemosensors of four pyrazine drugs in stoichiometric tests. The results were compared with the measurements made on an unmodified GCE. To obtain reliable results, the linearity of measurements was also verified in the concentration gradient and appropriate scanning speed was chosen to achieve the most accurate measurements.

Chemosensors published new progress about 4604-72-2. 4604-72-2 belongs to pyrazines, auxiliary class Pyrazine,Amine,Amide, name is Pyrazine-2-carbothioamide, and the molecular formula is C5H5N3S, Name: Pyrazine-2-carbothioamide.

Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem

Schneller, S. W. published the artcileA simple synthesis of thieno[2,3-b]pyrazine and thieno[2,3-b]pyridine, SDS of cas: 59944-75-1, the publication is Journal of Heterocyclic Chemistry (1976), 13(2), 273-5, database is CAplus.

The thienopyrazines I and -pyridines II (R = R1 = H) were prepared by diazotizing the amino derivatives I and II (R = NH2, R1 = CO2Et), resp., saponifying the resulting carboxylates I and II (R = H, R1 = CO2Et), resp., and decarboxylating the resulting carboxylic acids with Cu.

Journal of Heterocyclic Chemistry published new progress about 59944-75-1. 59944-75-1 belongs to pyrazines, auxiliary class Other Aromatic Heterocyclic,Amine, name is Thieno[2,3-b]pyrazin-7-amine, and the molecular formula is C6H5N3S, SDS of cas: 59944-75-1.

Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem

Cooper, Alan B. published the artcile1-Thiazol-2-yl-N-3-methyl-1H-pyrozole-5-carboxylic acid derivatives as antitumor agents, Name: Pyrazin-2-ylboronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(18), 4471-4477, database is CAplus and MEDLINE.

A class of substituted 1-thiazol-2-yl-N-3-methyl-1H-pyrozole-5-carboxylic acid derivatives was found to have potent anti-proliferative activity against a broad range of tumor cell lines. A compound from this class (14) was profiled across a broad panel of hematol. and solid tumor cancer cell lines demonstrating cell cycle arrest at the G0/G1 interphase and has potent anti-proliferative activity against a distinct and select set of cancer cell types with no observed effects on normal human cells. An example is the selective inhibition of human B-cell lymphoma cell line (BJAB). Compound 14 was orally bioavailable and tolerated well in mice. Synthesis and structure activity relationships (SAR) in this series of compounds are discussed.

Bioorganic & Medicinal Chemistry Letters published new progress about 762263-64-9. 762263-64-9 belongs to pyrazines, auxiliary class Pyrazine,Boronic acid and ester,Boronic Acids, name is Pyrazin-2-ylboronic acid, and the molecular formula is C4H5BN2O2, Name: Pyrazin-2-ylboronic acid.

Referemce:
https://en.wikipedia.org/wiki/Pyrazine,
Pyrazine | C4H4N2 – PubChem