Month: January 2023

Design and synthesis of potent carboxylic acid DGAT1 inhibitors with high cell permeability was written by Bali, Ustav;Barba, Oscar;Dawson, Graham;Gattrell, William T.;Horswill, James G.;Pan, David A.;Procter, Martin J.;Rasamison, Chrystelle M.;Sambrook Smith, Colin P.;Taylor-Warne, Amanda;Wong-Kai-In, Philippe. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2012.Product Details of 1209459-10-8 This article mentions the following:

A series of potent carboxylic acid, e.g., I, as DGAT1 inhibitors with high permeability were developed from a virtual screening hit. Strategies were employed to reduce Pgp substrate recognition and increase passive permeability, resulting in the discovery of a series showing good inhibition of cellular triglyceride synthesis. The mutagenic potential of prospective metabolites was evaluated and one aniline was shown to be devoid of mutagenicity. In the experiment, the researchers used many compounds, for example, 2-Bromo-5-fluoropyrazine (cas: 1209459-10-8Product Details of 1209459-10-8).

2-Bromo-5-fluoropyrazine (cas: 1209459-10-8) belongs to pyrazine derivatives. Pyrazines are volatile compounds that are used in the cosmetic, food, flavor, and fragrance industries. A number of pyrazine-based derivatives were used as dyes or fluorescent probes.Product Details of 1209459-10-8

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

1D polymeric copper(II) complexes containing bridging tridentate pyrazinato and terminal chloro or azido anions. Synthesis, spectral, structural and thermal study of [CuCl(pyrazinato)(H₂O)]_n and [Cu(N₃)(pyrazinato)(H₂O)]_n complexes was written by Goher, Mohamed A. S.;Abu-Youssef, Morsy A. M.;Mautner, Franz A.. And the article was included in Polyhedron in 1998.Formula: C7H8N2O2 This article mentions the following:

Polymeric [CuCl(pyrazinato)(H₂O)]_n (1) and [Cu(N₃)(pyrazinato)(H₂O)]_n (2) were synthesized and characterized by spectroscopic methods and x-ray crystallog. (1: monoclinic, space group P2₁/n, R₁ = 0.0368; 2: monoclinic, space group I2/a, R₁ = 0.0908). The overall spectral results indicate that these complexes contain tridentate pyrazinato ligands, terminal chloride or azide groups and aqua mols. In the structure of complex 1, each copper atom, which is chelated by oxygen and nitrogen atoms of a pyrazinato anion, links a chloride, an oxygen atom from an aqua mol. and the 2nd nitrogen from a pyrazinato group of a neighboring unit giving rise to a 1-dimensional polymeric structure. The structure of complex 2, which is very similar to 1, features a five coordinate copper(II) atom, a N,N,O-tridentate bridging pyrazinato ligand, a terminal azido ligand and an aqua mol. in a 1-dimensional polymer. There are different types of hydrogen bonds in both complexes. The thermal decomposition of 1 and 2 was studied thermogravimetrically in nitrogen atm. In the experiment, the researchers used many compounds, for example, Ethyl pyrazine-2-carboxylate (cas: 6924-68-1Formula: C7H8N2O2).

Ethyl pyrazine-2-carboxylate (cas: 6924-68-1) belongs to pyrazine derivatives. Pyrazine is an N-heterocyclic moiety, and it can be easily prepared from ethylenediamine and 1,2-diketone, α-hydroxyketone, α-methyl ketone. A large number of pyrazine derivatives are known for their antitumor, antibiotic, anticonvulsant, antituberculosis, and diuretic activities.Formula: C7H8N2O2

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Design, Synthesis, and Biological Evaluation of Dabigatran Etexilate Mimics, a Novel Class of Thrombin Inhibitors was written by Wang, Shaochi;Dai, Peng;Xu, Yungen;Chen, Qiufang;Zhu, Qihua;Gong, Guoqing. And the article was included in Archiv der Pharmazie (Weinheim, Germany) in 2015.Safety of (3,5,6-Trimethylpyrazin-2-yl)methanol This article mentions the following:

Human α-thrombin is a particularly promising target for anticoagulant therapy, and identification of oral small-mol. inhibitors of thrombin remains a research focus. On the basis of the x-ray crystal structure of human α-thrombin and its inhibitor dabigatran, we designed and synthesized a series of dabigatran etexilate mimics containing a novel tricyclic fused scaffold. The biol. evaluations reveal that all of the compounds possess moderate activity of antiplatelet aggregation induced by thrombin in vitro. Moreover, compound (I), which contains 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP), a cleavable moiety with antiplatelet activity, shows the best anticoagulant effect among the tested compounds in vivo. Those synthesized compounds that have better in vitro activity were subjected to bleeding complication tests, and the results demonstrate that the novel compounds are less likely to have bleeding risk than dabigatran etexilate. In the experiment, the researchers used many compounds, for example, (3,5,6-Trimethylpyrazin-2-yl)methanol (cas: 75907-74-3Safety of (3,5,6-Trimethylpyrazin-2-yl)methanol).

(3,5,6-Trimethylpyrazin-2-yl)methanol (cas: 75907-74-3) belongs to pyrazine derivatives. Pyrazine derivatives have antitumor, antibiotic, anticonvulsant, antituberculous and diuretic effects as well as kinase, enzymatic and potent tubulin and FtsZ polymerization inhibitory activities. Pyrazine and a variety of alkylpyrazines are flavor and aroma compounds found in baked and roasted goods. Tetramethylpyrazine (also known as ligustrazine) is reported to scavenge superoxide anion and decrease nitric oxide production in human Granulocytes.Safety of (3,5,6-Trimethylpyrazin-2-yl)methanol

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Ionization constants of heterocyclic substances. II. Hydroxy-derivatives of nitrogenous six-membered ring-compounds was written by Albert, Adrien;Phillips, J. N.. And the article was included in Journal of the Chemical Society in 1956.COA of Formula: C7H5N3 This article mentions the following:

Acidic and basic ionization constants were determined potentiometrically and in some cases spectrometrically for 87 hydroxy (and related) derivatives of pyridine, quinoline, isoquinoline, acridine, phenanthridine, pyridazine, pyrimidine, pyrazine, cinnoline, phthalazine, quinazoline, quinoxaline, phenazine, triazine, 1,4,5-triazanaphthalene, and 1,4,6-triazanaphthalene. The tautomeric equilibrium between enol and amide in α and γ-hydroxy derivatives greatly favor the amide form. The preparation of 2-methoxypyrazine, b₂₉ 60-1°, and 3-hydroxypyridine methochloride were described. A m.p. of 57° was reported for 2-methyl-1-isoquinolone. In the experiment, the researchers used many compounds, for example, Pyrido[2,3-b]pyrazine (cas: 322-46-3COA of Formula: C7H5N3).

Pyrido[2,3-b]pyrazine (cas: 322-46-3) belongs to pyrazine derivatives. Pyrazine is a symmetrical molecule with point group D2h. Pyrazine is less basic than pyridine, pyridazine and pyrimidine. Pyrazine and a variety of alkylpyrazines are flavor and aroma compounds found in baked and roasted goods. Tetramethylpyrazine (also known as ligustrazine) is reported to scavenge superoxide anion and decrease nitric oxide production in human Granulocytes.COA of Formula: C7H5N3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Studies on the reaction of π-deficient heterocycles with aromatic aldehydes in the presence of cyanide ion was written by Higashino, Takeo;Goi, Masami;Hayashi, Eisaku. And the article was included in Chemical & Pharmaceutical Bulletin in 1976.Quality Control of Pyrido[2,3-b]pyrazine This article mentions the following:

Dimerization of π-deficient heterocycles was catalyzed by cyanide ion in Me2SO. Thus, reaction of quinoxaline, 1-phenyl-1H-pyrazolo[3,4-d]pyrimidine(I), 1-methyl-1H-pyrazolo[3,4-d]pyrimidine (II), and pyrido[2,3-b]pyrazine (III) with cyanide ion gave 2,2′-biquinoxaline, 4,4′-bis[1-phenyl-1H-pyrazolo[3,4-d]pyrimidine] (IV), 4,4′-bis[1-methyl-1H-pyrazolo[3,4-d]pyrimidine], and 2,2′-bispyrido[2,3-b]pyrazine, resp., although the yields of these dimers were very poor. π-Deficient heterocycles with RC6H4CHO (V, R = o-, m-, p-MeO, Cl, Me, etc.) in the presence of cyanide ion in Me2SO underwent a cross benzoin condensation reaction. Thus, 4-isoquinolinecarbonitrile reacted with V to give α-aryl-4-cyano-1-isoquinolinemethanol and aryl 4-cyano-1-isoquinolyl ketone together with 1,1′-biisoquinoline-4,4′-dicarbonitrile. Similarly, quinoxaline and V gave α-aryl-2-quinoxalinemethanol and aryl 2-quinoxalinyl ketone, I and V gave α-aryl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine-4-methanol and aryl 1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl ketone, II and V produced α-aryl-1-methyl-1H-pyrazolo[3,4-d]pyrimidine-4-methanol and aryl 1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl ketone, and III and V formed aryl 2-pyrido[2,3-b]pyrazinyl ketone VI. In the experiment, the researchers used many compounds, for example, Pyrido[2,3-b]pyrazine (cas: 322-46-3Quality Control of Pyrido[2,3-b]pyrazine).

Pyrido[2,3-b]pyrazine (cas: 322-46-3) belongs to pyrazine derivatives. Pyrazines are volatile compounds that are used in the cosmetic, food, flavor, and fragrance industries. A number of pyrazine-based derivatives were used as dyes or fluorescent probes.Quality Control of Pyrido[2,3-b]pyrazine

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

BA-12 inhibits angiogenesis via glutathione metabolism activation was written by Cui, Herong;Guo, Wenbo;Zhang, Beibei;Li, Guoping;Li, Tong;Yuan, Yanyan;Zhang, Na;Yang, Yuwei;Feng, Wuwen;Chu, Fuhao;Wang, Shenglan;Xu, Bing;Wang, Penglong;Lei, Haimin. And the article was included in International Journal of Molecular Sciences in 2019.Safety of (3,5,6-Trimethylpyrazin-2-yl)methanol This article mentions the following:

There is a need for an efficient and low-cost leading compound discovery mode. However, drug development remains slow, expensive, and risky. Here, this manuscript proposes a leading compound discovery strategy based on a combination of traditional Chinese medicine (TCM) formulas and pharmacochem., using a ligustrazine-betulinic acid derivative (BA-12) in the treatment of angiogenesis as an example. Blocking angiogenesis to inhibit the growth and metastasis of solid tumors is currently one recognized therapy for cancer in the clinic. Firstly, based on a traditional Prunella vulgaris plaster, BA-12 was synthesized according to our previous study, as it exhibited better antitumor activities than other derivatives on human bladder carcinoma cells (T24); it was then uploaded for target prediction. Secondly, the efficacy and biotoxicity of BA-12 on angiogenesis were evaluated using human umbilical vein endothelial cells (HUVECs), a quail chick chorioallantoic membrane, and Caenorhabditis elegans. According to the prediction results, the main mechanisms of BA-12 were metabolic pathways. Thus, multiple metabolomics approaches were applied to reveal the mechanisms of BA-12. Finally, the predictive mechanisms of BA-12 on glutathione metabolism and glycerophospholipid metabolism activation were validated using targeted metabolomics and pharmacol. assays. This strategy may provide a reference for highly efficient drug discovery, with the aim of sharing TCM wisdom for unmet clin. needs. In the experiment, the researchers used many compounds, for example, (3,5,6-Trimethylpyrazin-2-yl)methanol (cas: 75907-74-3Safety of (3,5,6-Trimethylpyrazin-2-yl)methanol).

(3,5,6-Trimethylpyrazin-2-yl)methanol (cas: 75907-74-3) belongs to pyrazine derivatives. Pyrazine heterocycles and their benzo derivatives possess many interesting properties, including chemical reactivity profiles, and have diverse applications in total synthesis, medicine, chemical biology, materials, dyes, and imaging. A large number of pyrazine derivatives are known for their antitumor, antibiotic, anticonvulsant, antituberculosis, and diuretic activities.Safety of (3,5,6-Trimethylpyrazin-2-yl)methanol

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

The out-of-plane vibrations of aza-aromatic molecules was written by Chappell, P. J.;Ross, I. G.. And the article was included in Journal of Molecular Spectroscopy in 1977.SDS of cas: 322-46-3 This article mentions the following:

A transferable valence force field is developed for application to the out-of-plane vibrations of C6H6, naphthalene, and their aza analogs. Existing vibrational frequency assignments are rationalized and in some cases extensively revised. The mols. treated are quinoline and isoquinoline; 1,2-, 1,3-, 1,4-, 1,5-, 1,6-, 1,7-, 1,8-, 2,3- and 2,7-diazanaphthalene; 1,3,5-, 1,3,6-, 1,3,7-, 1,3,8-, 1,4,5- and 1,4,6-triazanaphthalene; and 1,3,5,8-, 1,4,5,8- and 2,3,6,7-tetraazanaphthalene. The assignment of the planar frequencies at 350-1000 cm-1 is also reviewed for these mols. The calculations on the azabenzenes are discussed. In the experiment, the researchers used many compounds, for example, Pyrido[2,3-b]pyrazine (cas: 322-46-3SDS of cas: 322-46-3).

Pyrido[2,3-b]pyrazine (cas: 322-46-3) belongs to pyrazine derivatives. Pyrazine derivatives have antitumor, antibiotic, anticonvulsant, antituberculous and diuretic effects as well as kinase, enzymatic and potent tubulin and FtsZ polymerization inhibitory activities. A number of pyrazine-based derivatives were used as dyes or fluorescent probes.SDS of cas: 322-46-3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Enhanced performance of quasi-solid-state dye-sensitized solar cells by tuning the building blocks in D-(π)-A’-π-A featured organic dyes was written by Lan, Tian;Lu, Xuefeng;Zhang, Lu;Chen, Yijing;Zhou, Gang;Wang, Zhong-Sheng. And the article was included in Journal of Materials Chemistry A: Materials for Energy and Sustainability in 2015.Product Details of 148231-12-3 This article mentions the following:

D-(π)-A’-π-A featured organic dyes with different numbers of 3,4-ethylenedioxythiophene (EDOT) bridges and different anchoring groups, i.e., cyanoacrylic acid or rhodanine-3-acetic acid, have been designed and synthesized for application in quasi-solid-state dye-sensitized solar cells (DSSCs). The absorption, electrochem. and photovoltaic properties are systematically studied. Upon the incorporation of an auxiliary EDOT unit into sensitizers FNE60 and FNE61 with D-A’-π-A configuration, sensitizers FNE62 and FNE63 with D-π-A’-π-A configuration exhibit much broader absorption spectra, which is beneficial to the light-harvesting capability and photocurrent generation. When the cyanoacrylic acid group in sensitizers FNE60 and FNE62 is replaced by a much stronger electron-withdrawing group, rhodanine-3-acetic acid, strengthened intramol. charge transfer interactions are realized, which results in the significantly bathochromically shifted maximum absorption wavelengths for sensitizers FNE61 and FNE63. However, the methylene group in the rhodanine-3-acetic acid unit interrupts the LUMO delocalization on the anchoring group in sensitizers FNE61 and FNE63, as revealed by theor. calculation, which may result in less effective electron injection from the LUMO to the conduction band of the TiO₂ semiconductor. Consequently, the quasi-solid-state DSSC based on FNE62 exhibits a highest power conversion efficiency of 8.2%, which illustrates good long-term stability after continuous light soaking for 1000 h. In the experiment, the researchers used many compounds, for example, 5,8-Dibromoquinoxaline (cas: 148231-12-3Product Details of 148231-12-3).

5,8-Dibromoquinoxaline (cas: 148231-12-3) belongs to pyrazine derivatives. Pyrazine is an N-heterocyclic moiety, and it can be easily prepared from ethylenediamine and 1,2-diketone, α-hydroxyketone, α-methyl ketone. Pyrazines are chemical compounds (technically called “methoxypyrazinesâ€? found in grape skin and stems that are responsible for many “greenâ€?flavors in wine. Levels of pyrazines are dependent on viticultural practices, climate, and grape variety.Product Details of 148231-12-3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Degradation behavior of poly(ethylene glycol) dicarboxylic acid (2-hydroxymethyl-3,5,6-trimethylpyrazine) ester in vitro was written by Xia, Cheng-jian;Wang, Song;Zhu, He-sun. And the article was included in Jingxi Huagong in 2004.Formula: C8H12N2O This article mentions the following:

Poly(ethylene glycol) (PEG) dicarboxylic acid (2-hydroxymethyl-3,5,6-trimethylpyrazine) ester (patented by BIT) was prepared in 92% yield by condensation of PEG-10000 and 2-hydroxymethyl-3,5,6-trimethylpyrazine with 1,1′-carbonyldiimidazole (CDI) as condensating agent. The product was characterized by m.p., FTIR and ¹HNMR: m.p. 53 âˆ?55 °C; FTIR absorption 1747 cm^-1 (C=O), 1254 cm^-1 (C-O-C); ¹HNMR δ = 1.9 (-CH₃, 3H, s), 2.2 (-CH₃, 6H, s), 4.2 (-CH₂-, 2H, s), 3.6 (-OCH₂-, multi – H, s). The hydrolytic degradation of the ester in vitro was performed and results indicated that the degradation rate was pH-dependent. In the experiment, the researchers used many compounds, for example, (3,5,6-Trimethylpyrazin-2-yl)methanol (cas: 75907-74-3Formula: C8H12N2O).

(3,5,6-Trimethylpyrazin-2-yl)methanol (cas: 75907-74-3) belongs to pyrazine derivatives. Pyrazine is a symmetrical molecule with point group D2h. Pyrazine is less basic than pyridine, pyridazine and pyrimidine. Pyrazines are chemical compounds (technically called “methoxypyrazinesâ€? found in grape skin and stems that are responsible for many “greenâ€?flavors in wine. Levels of pyrazines are dependent on viticultural practices, climate, and grape variety.Formula: C8H12N2O

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Molecular pharmacology of the amiloride analog 3-amino-6-chloro-5-[(4-chloro-benzyl)amino]-N-[[(2,4-dimethylbenzyl)-amino]iminomethyl]-pyrazinecarboxamide (CB-DMB) as a pan inhibitor of the Na⁺-Ca²⁺ exchanger isoforms NCX1, NCX2, and NCX3 in stably transfected cells was written by Secondo, Agnese;Pannaccione, Anna;Molinaro, Pasquale;Ambrosino, Paolo;Lippiello, Pellegrino;Esposito, Alba;Cantile, Maria;Khatri, Priti R.;Melisi, Daniela;Di Renzo, Gianfranco;Annunziato, Lucio. And the article was included in Journal of Pharmacology and Experimental Therapeutics in 2009.Reference of 1458-01-1 This article mentions the following:

With the help of single-cell microfluorimetry, ⁴⁵Ca²⁺ radiotracer fluxes, and patch-clamp in whole-cell configuration, the authors examined the effect of the amiloride derivative 3-amino-6-chloro-5-[(4-chloro-benzyl)amino]-N-[[(2,4-dimethylbenzyl) amino]-iminomethyl]-pyrazinecarboxamide (CB-DMB) on the activity of the three isoforms of the Na⁺/Ca²⁺ exchanger (NCX) and on several other membrane currents including voltage- and pH-sensitive ones. This amiloride analog suppressed the bidirectional activity of all NCX isoforms in a concentration-dependent manner. The IC₅₀ values of CB-DMB were in the nanomolar range for the outward and the inward components of the bidirectional NCX1, NCX2, and NCX3 activity. Deletion mutagenesis showed that CB-DMB inhibited NCX activity mainly at level of the f-loop but not through the interaction with Gly 833 located at the level of the α₂ repeat. CB-DMB suppressed in the micromolar range the other plasma membrane currents encoded by voltage-dependent Ca²⁺ channels, tetrodotoxin-sensitive Na⁺ channels, and pH-sensitive ASIC1a. Collectively, the data of the present study showed that CB-DMB, when used in the nanomolar range, is one of the most potent compounds that can block the activity of the three NCX isoforms when they work both in the forward and in the reverse modes of operation without interfering with other ionic channels. In the experiment, the researchers used many compounds, for example, Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1Reference of 1458-01-1).

Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1) belongs to pyrazine derivatives. Pyrazine heterocycles and their benzo derivatives possess many interesting properties, including chemical reactivity profiles, and have diverse applications in total synthesis, medicine, chemical biology, materials, dyes, and imaging. Pyrazine heterocycles and their benzo derivatives possess many interesting properties, including chemical reactivity profiles, and have diverse applications in total synthesis, medicine, chemical biology, materials, dyes, and imaging.Reference of 1458-01-1

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem