Category: Pyrazines

Srivastava, Ruby published the artcileChemical reactivity theory (CRT) study of small drug-like biologically active molecules, Application of Thieno[2,3-b]pyrazin-7-amine, the publication is Journal of Biomolecular Structure and Dynamics (2021), 39(3), 943-952, database is CAplus and MEDLINE.

New biochem. screening and design based technol. are used to identify the small mols. in targeting RNA. These approaches has develop potential drug like small mol. for RNA-targeted therapeutics. Chem. Reactivity Theory (CRT) is used to study these drug-like, biol. active small mols. that target RNA. Twenty two small mols. based on structure (), information (), fragment (), small mol. microarrays (), and use of phenotypic assays () are selected for the studies of several DFT-based global reactivity and local reactivity descriptors to provide complete explanation for the reactivity of these complexes by chem. reactivity method. Higher HOMO-LUMO gap indicated the structural stability for the studied complexes. The complexes reflect greater thermodn. stability. Further the results predicted that high aromaticity and hardness are measures of high stability and low reactivity for the studied complexes. It was observed that a good, more reactive, nucleophile can be described by a lower value of μ, ω while a good electrophile can be described by a high value of μ, ω. TDDFT results predicted that few complexes can be used as fluorescent biomarkers as their emission wavelength lies in the visible region.

Journal of Biomolecular Structure and Dynamics 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 C11H14O2, Application of Thieno[2,3-b]pyrazin-7-amine.

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

Parmar, Udaysinh published the artcileRoom-Temperature Amination of Chloroheteroarenes in Water by a Recyclable Copper(II)-Phosphaadamantanium Sulfonate System, Application In Synthesis of 343856-62-2, the publication is Journal of Organic Chemistry (2021), 86(13), 8900-8925, database is CAplus and MEDLINE.

The current report discusses about an efficient copper-based catalytic system (Cu/PTABS) for the amination of chloroheteroarenes RCl (R = pyrazinyl, 1,3-benzothiazol-2-yl, 9H-purin-6-yl, etc.) at ambient temperature in water as the sole reaction solvent, a combination that is first to be reported. A wide variety of chloroheteroarenes could be coupled efficiently with primary and secondary amines, e.g., morpholine as well as selected amino acid esters, e.g., L-valine Me ester hydrochloride under mild reaction conditions. Catalytic efficiency of the developed protocol also promotes late-stage functionalization of active pharmaceutical ingredients, e.g., I (APIs) such as antibiotics (floxacins) and anticancer drugs. The catalytic system also performs efficiently at a very low concentration of 0.0001 mol% (TON = 980,000) and can be recycled 12 times without any appreciable loss in activity. Theor. calculations reveal that the π-acceptor ability of the ligand PTABS is the main reason for the appreciably high reactivity of the catalytic system. Preliminary characterization of the catalytic species in the reaction was carried out using UV-VIS and ESR spectroscopy, providing evidence for the Cu(II) oxidation state.

Journal of Organic Chemistry published new progress about 343856-62-2. 343856-62-2 belongs to pyrazines, auxiliary class Pyrazine,Piperidine,Chloride, name is 2-Chloro-6-(piperidin-1-yl)pyrazine, and the molecular formula is C9H12ClN3, Application In Synthesis of 343856-62-2.

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

Martelli, Alma published the artcileArylthioamides as H₂S Donors: L-Cysteine-Activated Releasing Properties and Vascular Effects in Vitro and in Vivo, Recommanded Product: Pyrazine-2-carbothioamide, the publication is ACS Medicinal Chemistry Letters (2013), 4(10), 904-908, database is CAplus and MEDLINE.

A small library of arylthioamides (12 compounds) was easily synthesized, and their H₂S-releasing properties were evaluated both in the absence or in the presence of an organic thiol such as L-cysteine. A number of arylthioamides showed a slow and L-cysteine-dependent H₂S-releasing mechanism, similar to that exhibited by the reference slow H₂S-releasing agents, such as diallyl disulfide (DADS) and the phosphinodithioate derivative GYY 4137. Compound 4-HOC₆H₄CSNH₂ strongly abolished the noradrenaline-induced vasoconstriction in isolated rat aortic rings and hyperpolarized the membranes of human vascular smooth muscle cells in a concentration-dependent fashion. Finally, a significant reduction of the systolic blood pressure of anesthetized normotensive rats was observed after its oral administration. Altogether these results highlighted the potential of four arylthioamides as H₂S-donors for basic studies, and for the rational design/development of promising pharmacotherapeutic agents to treat cardiovascular diseases.

ACS Medicinal Chemistry Letters 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, Recommanded Product: Pyrazine-2-carbothioamide.

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

Yamamoto, Setsuko published the artcileIn vitro antimycobacterial activities of pyrazinamide analogs. Results of screening tests, Safety of Pyrazine-2-carbothioamide, the publication is Kekkaku (1996), 71(3), 253-258, database is CAplus and MEDLINE.

In an attempt to find new drugs which are more effective than pyrazinamide against Mycobacterium tuberculosis and also active against the M. avium complex (MAC), we synthesized various pyrazinamide analogs and pyrazine derivatives and assayed their antimycobacterial activities in vitro against M. tuberculosis, M. avium and M. intracellulare. As is well known, pyrazinamide is more active in acidic medium than in neutral medium, but the growth of mycobacteria in acidic media is poor and inconsistent. Preliminary experiments revealed that the relative antimycobacterial activities of test drugs compared with pyrazinamide were essentially the same in pH 5.5 medium as in pH 6.0 medium. Therefore, Middlebrook 7H9 broth adjusted to pH 6.0 was used throughout the present studies. Among 39 compounds synthesized, four drugs were insoluble in any solvent suitable for culture experiments and could not be tested; the remaining 35 compounds were screened. The growth of mycobacteria was followed by measuring the optical d. at 530 nm (OD), and the OD of the culture in the presence of 200 μg/mL of the test-drug (OD-TD) was compared with that in the presence of pyrazinamide (OD-PZA). Each test drug was ranked as A, B, C, D or E according to the ratio (OD-TD/OD-PZA)X100%, if the ratio was equal to or less than 10%, 11-20%, 21-40%, 41-60% or 61-80%, resp. Any drugs showing a ratio above 80% were excluded from further examination For M. tuberculosis, 11 drugs were ranked as A and 4 more as B. For M. avium, 2 drugs were ranked as A and 2 more as B. for M. intracellulare, 5 drugs were ranked as A and 2 more as B. Among highly ranked ones, 4 compounds, namely, pyrazinoic acid octyl ester, pyrazinoic acid pivaloyloxymethyl ester, pyrazine thiocarboxamide and N-hydroxymethyl pyrazine thiocarboxiamide were ranked at A against M. tuberculosis and M. intracellulare, and ranked as A, B or C against M. avium, and considered as hopeful candidates of new antimycobacterial drugs. Their bacteriostatic and bactericidal activities against M. tuberculosis as well as M. avium and M. intracellulare have been studied in detail and reported in a sep. paper. In vivo activities against murine exptl. tuberculosis of these 4 drugs is now under investigation. Further, two drugs, N-hydroxy pyrazinamide and N-hydroxy pyrazinamide-4-oxide were ranked as A against M. tuberculosis and ranked A or B against M. intracellulare, and their more precise in vitro antimycobacterial activities are now under examination

Kekkaku 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 C4H7BrO2, Safety of Pyrazine-2-carbothioamide.

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

Yamamoto, Setsuko published the artcileIn vitro antimycobacterial activities of pyrazinamide analogs, Related Products of pyrazines, the publication is Antimicrobial Agents and Chemotherapy (1995), 39(9), 2088-91, database is CAplus and MEDLINE.

We synthesized various pyrazine derivatives and pyrazinamide analogs and assayed their antimycobacterial activities in vitro in order to find new drugs which are more active against Mycobacterium tuberculosis than pyrazinamide and also active against Mycobacterium avium and Mycobacterium intracellulare. Of the drugs synthesized, four, namely, pyrazine thiocarboxamide, N-hydroxymethyl pyrazine thiocarboxamide, pyrazinoic acid n-octyl ester, and pyrazinoic acid pivaloyloxymethyl ester, were not only bacteriostatic but also bactericidal against these three species of mycobacteria in vitro under conditions in which pyrazinamide showed no or little activity. In conclusion, these four drugs are possible candidates for new antimycobacterial agents, and animal experiments are now under way.

Antimicrobial Agents and Chemotherapy 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 C9H20Cl2Si, Related Products of pyrazines.

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

Bianchini, Gianluca published the artcileDiscovery of Novel TRPM8 Blockers Suitable for the Treatment of Somatic and Ocular Painful Conditions: A Journey through pK_a and LogD Modulation, Recommanded Product: Pyrazine-2-carbothioamide, the publication is Journal of Medicinal Chemistry (2021), 64(22), 16820-16837, database is CAplus and MEDLINE.

Transient receptor potential melastatin 8 (TRPM8) is crucially involved in pain modulation and perception, and TRPM8 antagonists have been proposed as potential therapeutic approaches for pain treatment. Previously, we developed two TRPM8 antagonists and proposed them as drug candidates for topical and systemic pain treatment. Here, we describe the design and synthesis of these two TRPM8 antagonists (27 (I) and 45 (II)) and the rational approach of modulation/replacement of bioisosteric chem. groups, which allowed us to identify a combination of narrow ranges of pK_a and LogD values that were crucial to ultimately optimize their potency and metabolic stability. Following the same approach, we then pursued the development of new TRPM8 antagonists suitable for the topical treatment of ocular painful conditions and identified two new compounds (51 (III) and 59 (IV)), N-alkoxy amide derivatives, that can permeate across ocular tissue and reduce the behavioral responses induced by the topical ocular menthol challenge in vivo.

Journal of Medicinal 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, Recommanded Product: Pyrazine-2-carbothioamide.

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

Wang, Tao published the artcileDiscovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir, Safety of Pyrazin-2-ylboronic acid, the publication is Journal of Medicinal Chemistry (2018), 61(14), 6308-6327, database is CAplus and MEDLINE.

The optimization of the 4-methoxy-6-azaindole series of HIV-1 attachment inhibitors (AIs) that originated with 1 to deliver temsavir (3, BMS-626529) is described. The most beneficial increases in potency and pharmacokinetic (PK) properties were attained by incorporating N-linked, sp²-hybridized heteroaryl rings at the 7-position of the heterocyclic nucleus. Compounds that adhered to a coplanarity model afforded targeted antiviral potency, leading to the identification of 3 with characteristics that provided for targeted exposure and PK properties in three preclin. species. However, the phys. properties of 3 limited plasma exposure at higher doses, both in preclin. studies and in clin. trials as the result of dissolution- and/or solubility-limited absorption, a deficiency addressed by the preparation of the phosphonooxymethyl prodrug 4 (BMS-663068, fostemsavir). An extended-release formulation of 4 is currently in phase III clin. trials where it has shown promise as part of a drug combination therapy in highly treatment-experienced HIV-1 infected patients.

Journal of Medicinal Chemistry 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 C7H10BNO4S, Safety of Pyrazin-2-ylboronic acid.

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