Tag: M.W=100-150

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

Kayser, A. published the artcileGrowth inhibition of staphylococci by sodium thiosulfate, Product Details of C5H5N3S, the publication is Journal of Applied Bacteriology (1965), 28(2), 286-93, database is CAplus and MEDLINE.

Several strains of staphylococci and micrococci used as test organisms for I disinfectant assay were inhibited by the Na thiosulfate used to neutralize residual I. The action was not due to changes in pH or redox potential, but was most pronounced in media containing high concentrations of cystine.

Journal of Applied Bacteriology 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

Johns, Brian A. published the artcile1,3,4-Oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position, Safety of Pyrazin-2-ylboronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(6), 1807-1810, database is CAplus and MEDLINE.

The use of a 1,3,4-oxadiazole in combination with an 8-hydroxy-1,6-naphthyridine ring system has been shown to deliver potent enzyme and antiviral activity through inhibition of viral DNA integration. This report presents a detailed structure-activity investigation of the C5 position resulting in low nM potency for several analogs with an excellent therapeutic index.

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, Safety of Pyrazin-2-ylboronic acid.

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

Taeuscher, Eric published the artcileSynthesis and characterization of new 4-hydroxy-1,3-thiazoles, Computed Properties of 4604-72-2, the publication is Synthesis (2010), 1603-1608, database is CAplus.

A series of highly substituted 4-hydroxy-1,3-thiazoles was synthesized by cyclocondensation of α-bromo carboxylates with thioamides or of thiolactate with 2-quinoxalinecarbonitrile. Whereas their anions display strong fluorescence in the bathochromic part of the visible spectrum, the emission is shifted hypsochromically upon alkylation. This easy switch between the anion and its derivatives makes them suitable for widespread applications. The thiazoles possess prerequisites for the complexation of metals due to the coexistence of aza-heterocycles and of 1,3-diketone substructures. In addition, the OH group allows further functionalization, as exemplified by the incorporation of an azide or an acetylene into the product, and by the synthesis of a star-shaped derivative The mol. and crystal structure of 2-(1,5-dimethylpyrrol-2-yl)-5-phenyl-4-thiazolol was presented [monoclinic, space group P2₁/n, a 6.7533(2), b 20.6146(6), c 9.9435(3) Å, β 109.062(2)°, V 1308.39(7) ų, Z 4].

Synthesis 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 C3H9ClOS, Computed Properties of 4604-72-2.

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

Liu, Zong-ying published the artcileSynthesis and antiparasitic activity of new bis-arylimidamides: DB766 analogs modified in the terminal groups, Computed Properties of 4604-72-2, the publication is European Journal of Medicinal Chemistry (2014), 167-173, database is CAplus and MEDLINE.

Fifteen novel bis-arylimidamide derivatives with various 6-membered and 5-membered heterocyclic rings replacing the terminal pyridyl rings of the lead compound DB766, were prepared and evaluated vs. Trypanosoma cruzi, Leishmania amazonensis, Trypanosoma brucei rhodesiense and Plasmodium falciparum. Compound I(R = 2-pyrimidyl) with pyrimidine replacing the pyridine rings showed good activity vs. T. cruzi, T. brucei rhodesiense and P. falciparum (IC₅₀ = 200 nM, 32 nM and 8.5 nM, resp.). Three compounds I(R = 2-methyl-4-thiozolyl, 2-methylamino-4-thiozolyl, 2-acetylamino-4-thiozolyl) with thiazole replacing the pyridine rings gave low micromolar (0.17-0.3 μM) IC₅₀ values vs. L. amazonensis, however only 7g exhibited an acceptable selectivity index (SI = 27). Compounds I(R = 2-pyrimidyl, 2-acetylamino-4-thiozolyl, 2-imidazolyl) exhibited potent activity against T. brucei rhodesiense (IC₅₀ = 12-60 nM). Ten of the 15 compounds with pyrimidine, pyrrole, thiazole and imidazole terminal units were highly active against P. falciparum (IC₅₀ = 9-87 nM). Both pyrimidine and pyridine terminal groups are advantageous for anti-T. cruzi activity and several different heterocyclic terminal units are effective vs. P. falciparum, both findings merit further investigation.

European 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, Computed Properties of 4604-72-2.

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

East, Stephen P. published the artcileDNA gyrase (GyrB)/topoisomerase IV (ParE) inhibitors: Synthesis and antibacterial activity, Category: pyrazines, the publication is Bioorganic & Medicinal Chemistry Letters (2009), 19(3), 894-899, database is CAplus and MEDLINE.

The synthesis and antibacterial activities of three chemotypes of DNA supercoiling inhibitors based on imidazo[1,2-a]pyridine and [1,2,4]triazolo[1,5-a]pyridine scaffolds, e.g. I (R = H, Ph, 2-HOC₆H₄, 2-pyridyl, 5-pyrimidyl, 1-imidazolyl, CO₂Me, CONHEt, etc.), that target the ATPase subunits of DNA gyrase and topoisomerase IV (GyrB/ParE) is reported. The most potent scaffold was selected for optimization leading to a series with potent Gram-pos. antibacterial activity and a low resistance frequency.

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, Category: pyrazines.

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