Month: November 2022

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

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

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

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

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

Cumming, Jared N. published the artcileStructure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor, Product Details of C4H5BN2O2, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(7), 2444-2449, database is CAplus and MEDLINE.

From an initial lead 2-imino-1-methyl-4,4-diphenyl-5-imidazolidinone, a structure-based design approach led to identification of the novel, high-affinity iminohydantoin BACE1 inhibitor I that lowers CNS-derived Aβ following oral administration to rats. SAR development in the S3 and F’ subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for I are reported.

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, Product Details of C4H5BN2O2.

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

Chylewska, Agnieszka published the artcileAttractive S···π and π-π interactions in the pyrazine-2-thiocarboxamide structure: Experimental and computational studies in the context of crystal engineering and microbiological properties, Name: Pyrazine-2-carbothioamide, the publication is Journal of Molecular Structure (2016), 96-104, database is CAplus.

Pyrazine-2-thiocarboxamide (PTCA) was obtained after recrystallization and was characterized by elemental anal., IR spectroscopy and thermogravimetry. Five dimers of PTCA were found in X-ray diffraction studies. These results were then compared with the known structures of a popular drug, i.e. pyrazine-2-carboxamide (PZA). S···π and π-π interactions were observed in the PTCA crystal structure as a novelty in X-ray measurements and our attention was focused on their role in stabilizing the PCTA structure. The geometry, energy and IR spectra for two conformers (E, Z) of PTCA and five dimers (D1-D5) were calculated for the gas phase with the DFT method at 6-311 + G(d,p) basis set. The results of calculations showed that D1 is the most stable dimer among five dimers of PTCA which were found exptl. Thermal decomposition of PTCA was examined with the use of the TG/IR anal. (20-1000 °C) and the results were discussed. To test the antimicrobial activity of PTCA a biol. assay was performed to determine its potentially pharmaceutical applications. The min. inhibitory (MIC) and minimal bactericidal (fungicidal) concentrations (MBC) for PTCA were determined against six microorganisms.

Journal of Molecular Structure 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

Kakimoto, Shichiro published the artcileStructure and activity of carbothionamides, Computed Properties of 4604-72-2, the publication is Tuberkulose-Forschungsinstitut Borstel, Jahresbericht (1961), 240-81, database is CAplus.

Approx. 70 carbothionamides were tested for inhibition of growth of Mycobacterium. IR estimation of polarization of the C:S bond showed that increasing negativity correlated with antibacterial activity. Toxicity of compounds was due to H₂S production in acid solution 95 references

Tuberkulose-Forschungsinstitut Borstel, Jahresbericht 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, Computed Properties of 4604-72-2.

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

Coats, Steven J. published the artcileParallel methods for the preparation and SAR exploration of N-ethyl-4-[(8-alkyl-8-aza-bicyclo[3.2.1]oct-3-ylidene)-aryl-methyl]-benzamides, powerful mu and delta opioid agonists, Recommanded Product: Pyrazin-2-ylboronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2004), 14(22), 5493-5498, database is CAplus and MEDLINE.

Libraries of azabicyclooctylidenemethylbenzamides such as I are prepared as μ- and δ-opioid agonists using solid-phase and solution-phase methods; qual. relationships between the structures of azabicyclooctylidenebenzamides and their μ- and δ-opioid agonist activities are discussed. 4-(Methoxycarbonyl)benzyl bromide is converted to di-Me 4-(methoxycarbonyl)benzylphosphonate with tri-Me phosphite; base-mediated olefination of N-(ethoxycarbonyl)tropinone, bromination and base treatment, and cleavage of the Et carbamate followed by replacement with an Fmoc moiety yields the intermediate (carboxyphenylbromomethylene)azabicyclooctanecarboxylate II (R = HO; R¹ = Br; R² = Fmoc). Attachment of II (R = HO; R¹ = Br; R² = Fmoc) to a resin-bound ethylamine yields a solid-phase intermediate which undergoes piperidine-mediated deprotection of the Fmoc group, reductive amination with aldehydes, palladium-catalyzed Suzuki coupling with aryl- or heteroarylboronic acids, and trifluoroacetic acid deprotection to yield azabicyclooctylidenemethylbenzamides. Coupling of II (R = HO; R¹ = Br; R² = Fmoc) to ethylamine and deprotection yields intermediate II (R = EtNH; R¹ = Br; R² = H); microwave-mediated reductive amination of II (R = EtNH; R¹ = Br; R² = H) with aldehydes and sodium triacetoxyborohydride, quenching with water, and microwave-mediated Suzuki coupling in the presence of tetrakis(triphenylphosphine)palladium yields azabicyclooctylidenemethylbenzamides. Azabicyclooctylidenemethylbenzamides substituted with a wide variety of aryl groups at the methylene carbon are effective as μ- and δ-opioid agonist. Small substituents at the nitrogen of the azabicyclooctyl ring in azabicyclooctylidenemethylbenzamides are preferred for good μ- and δ-opioid agonist activity; basic and acidic substituents decrease activity (although the effects of basic groups can be mitigated by appropriate aryl substitution at the methylene carbon). I has K_i values of 6.0 nM for the μ-opioid receptor and 3.8 nM for the δ-opioid receptor and is an effective oral antinociceptive agent at a dose of 150 μmol/kg in a 48° mouse hot plate test.

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, Recommanded Product: Pyrazin-2-ylboronic acid.

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

Foks, Henryk published the artcileAminomethylation of pyridine and pyrazine carbothioamides. I. Pyrazine carbothioamide and pyridine 2-ethyl-4-carbothioamide in the Mannich reaction, Computed Properties of 4604-72-2, the publication is Gdansk. Tow. Nauk., Rozpr. Wydz. 3 (1969), 203-9, database is CAplus.

Aminomethylation of pyrazine carbothioamide with HCHO and piperidine gave 70% I. 2-Ethylpyridine 4-carbothioamide, HCHO, and piperidine gave II. Similar Mannich bases were prepared with other secondary amines.

Gdansk. Tow. Nauk., Rozpr. Wydz. 3 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, Computed Properties of 4604-72-2.

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