Month: January 2023

Redox-sensitive carrier-free nanoparticles self-assembled by disulfide-linked paclitaxel-tetramethylpyrazine conjugate for combination cancer chemotherapy was written by Zou, Liang;Liu, Xiaowei;Li, Jingjing;Li, Wei;Zhang, Lele;Fu, Chaomei;Zhang, Jinming;Gu, Zhongwei. And the article was included in Theranostics in 2021.COA of Formula: C8H12N2O This article mentions the following:

Combinations of two or more therapeutic agents targeting different signaling pathways involved in tumor progression can have synergistic anticancer effects. However, combination chemotherapies are greatly limited by the different pharmacokinetics, tumor targeting, and cellular uptake capacities of the combined drugs. We have previously demonstrated the potential synergistic efficacy of paclitaxel (PTX) and the natural anti-angiogenic agent tetramethylpyrazine (TMP) for suppressing ovarian carcinoma growth. An efficient, facile, and smart nanosystem to deliver PTX and TMP simultaneously in vivo is greatly desired. We constructed a redox-sensitive nanosystem based on the amphiphilic PTX-ss-TMP conjugate, in which PTX and TMP are linked by a disulfide bond. We characterized the structure of the drug conjugate by ¹H NMR and LC-MS, and then prepared PTX-ss-TMP NPs by a one-step nanopptn. method. We investigated the redox sensitivity, tumor-targeting ability, anticancer efficacy, and anti-angiogenesis activity of PTX-ss-TMP NPs in vitro and in vivo. The amphiphilic PTX-ss-TMP conjugate readily self-assembled into stable nanoparticles in aqueous solution with a low critical association concentration of 1.35 μg/mL, well-defined spherical structure, small particle size (152 nm), high drug loading, redox-responsive drug release, high biocompatibility, and high storage stability. In cancer cells pretreated with GSH-OEt, PTX-ss-TMP NPs exhibited higher cytotoxicity, apoptosis rate, and cell-cycle arrest than monotherapy or combination therapy with free drugs, which was attributed to their improved cellular uptake and rapid intracellular drug release. Addnl., PTX-ss-TMP NPs also had a stronger anti-angiogenesis effect in HUVECs than free drug, which was mediated by VEGFR2-involved downstream signals. Finally, PTX-ss-TMP NPs showed tumor-specific accumulation and excellent antitumor activity in A2780 xenograft mice compared with free drug. These in vitro and in vivo results provide clear evidence that this redox-responsive carrier-free nanosystem with intrinsic amphiphilicity has great potential for combination cancer chemotherapy. In the experiment, the researchers used many compounds, for example, (3,5,6-Trimethylpyrazin-2-yl)methanol (cas: 75907-74-3COA of Formula: C8H12N2O).

(3,5,6-Trimethylpyrazin-2-yl)methanol (cas: 75907-74-3) 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. Pyrazine-based skeletons were incorporated into agents targeting a range of ailments. Many derivatives were synthesized and evaluated as potential cancer treatments.COA of Formula: C8H12N2O

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Biochemical identification of two types of phenamil binding sites associated with amiloride-sensitive sodium channels was written by Barbry, Pascal;Chassande, Olivier;Duval, Daniele;Rousseau, Bernard;Frelin, Christian;Lazdunski, Michel. And the article was included in Biochemistry in 1989.Safety of Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate This article mentions the following:

The biochem. basis for the existence of distinct forms of the epithelium Na⁺ channel that differ in their sensitivity to amiloride was analyzed by using phenamil, the most potent inhibitor known so far for the epithelium Na⁺ channel. [³H]Phenamil of high radioactive specific activity (30 Ci/mmol) was prepared and used to titrate [³H]phenamil-binding sites in pig kidney membranes. Kinetic experiments, equilibrium binding studies, and competition experiments indicated the presence in crude membrane preparations of 12 classes of independent binding sites. The 1st binding site was characterized by a high affinity for phenamil (dissociation constant 1 (K_d1) = 0.4 nM) and for amiloride (K_d1 = 0.1 μM). The 2nd binding site recognized phenamil and amiloride with lower affinities (K_d2(phenamil) = 28 nM, K_d2(amiloride) = 4 μM). The ratio of the resp. amounts of low- and high-affinity binding sites was 14 in different membrane preparations (range: 6-22). The 2 types of binding sites for [³H]phenamil copurified and were still observed after purification of the epithelium Na⁺ channel to homogeneity. Thus, â‰? types of pharmacol. distinguishable Na⁺ channels exist in the kidney. They correspond either to 2 isoforms of the apical Na⁺ channel or to 1 single type of channel under 2 different states of covalent regulation. In the experiment, the researchers used many compounds, for example, Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1Safety of Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate).

Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate (cas: 1458-01-1) belongs to pyrazine derivatives. Pyrazinesare six-membered aromatic heterocyclic organic compounds with two nitrogen atoms at 1,4-positions. Pyrazine is a weaker base (pKb = 13.4) than pyridine (pKb = 8.8), pyrimidine (pKb = 12.7). 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.Safety of Methyl 3,5-diamino-6-chloropyrazine-2-carboxylate

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing a cleavable moiety with anti-platelet activity was written by Yang, Xiao-Zhi;Yang, Wen-Hui;Xu, Yun-Gen;Diao, Xiao-Juan;He, Guang-Wei;Gong, Guo-Qing. And the article was included in European Journal of Medicinal Chemistry in 2012.Formula: C8H12N2O This article mentions the following:

A novel series of prodrugs I(R = tBu, hexyl, pentyl, iPr, Et, Bn, Me) consisting of dabigatran and 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) were synthesized. The pharmacol. results show that all of them possess the effect of anti-platelet aggregation induced by thrombin in vitro. Moreover, one of those compounds, I(R = hexyl) (ED₅₀ = 2.1 ± 1.3 mg/kg) shows more potent activity for inhibiting thrombosis in vivo than that of dabigatran etexilate (ED₅₀ = 4.4 ± 2.2 mg/kg). 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 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.Formula: C8H12N2O

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Alkylamino derivatives of pyrazinamide: Synthesis and antimycobacterial evaluation was written by Servusova, Barbora;Paterova, Pavla;Mandikova, Jana;Kubicek, Vladimir;Kucera, Radim;Kunes, Jiri;Dolezal, Martin;Zitko, Jan. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2014.Synthetic Route of C5H6N4O This article mentions the following:

A series of pyrazinamide derivatives with alkylamino substitution was designed, synthesized and tested for their ability to inhibit the growth of selected mycobacterial, bacterial and fungal strains. The target structures were prepared from the corresponding 5-chloro or 6-chloropyrazine-2-carboxamide by nucleophilic substitution of chlorine by various non-aromatic amines (alkylamines). To determine the influence of alkyl substitution, corresponding amino derivatives and compounds with phenylalkylamino substitution were prepared Some of the compounds exerted antimycobacterial activity against Mycobacterium tuberculosis H37Rv significantly better than standard pyrazinamide and corresponding starting compounds Basic structure-activity relations are presented. Only weak antibacterial and no antifungal activity was detected. In the experiment, the researchers used many compounds, for example, 5-Aminopyrazine-2-carboxamide (cas: 89323-09-1Synthetic Route of C5H6N4O).

5-Aminopyrazine-2-carboxamide (cas: 89323-09-1) belongs to pyrazine derivatives. Pyrazine has the elements of symmetry for the point group D2h. It has three mutually perpendicular two-fold axes. It also has three mutually perpendicular planes of symmetry. As a result, pyrazine also has a centre of symmetry. Pyrazine-based skeletons were incorporated into agents targeting a range of ailments. Many derivatives were synthesized and evaluated as potential cancer treatments.Synthetic Route of C5H6N4O

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Substituted pyrido[2,3-b]pyrazines was written by Kaye, Irving A.. And the article was included in Journal of Medicinal Chemistry in 1964.Electric Literature of C7H5N3 This article mentions the following:

Pyrido[2,3-b]pyrazines were prepared by condensing 2,3-diaminopyridine or 2,3,6-triaminopyridine with an α-diketone or (CO₂Et)₂; Pb 6-aminopyrido[2,3-b]pyrazine-2,3-dicarboxylate was obtained by KMnO₄ oxidation of 6-amino-2,3-dimethylpyrido[2,3-b]pyrazine. In the experiment, the researchers used many compounds, for example, Pyrido[2,3-b]pyrazine (cas: 322-46-3Electric Literature of C7H5N3).

Pyrido[2,3-b]pyrazine (cas: 322-46-3) belongs to pyrazine derivatives. Pyrazinesare six-membered aromatic heterocyclic organic compounds with two nitrogen atoms at 1,4-positions. Pyrazine is a weaker base (pKb = 13.4) than pyridine (pKb = 8.8), pyrimidine (pKb = 12.7). Pyrazines are chemical compounds (technically called “methoxypyrazines”) found in grape skin and stems that are responsible for many “green” flavors in wine. Levels of pyrazines are dependent on viticultural practices, climate, and grape variety.Electric Literature of C7H5N3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Side chain engineering of quinoxaline-based small molecular nonfullerene acceptors for high-performance poly(3-hexylthiophene)-based organic solar cells was written by Xiao, Bo;Zhang, Qianqian;Li, Gongqiang;Du, Mengzhen;Geng, Yanfang;Sun, Xiangnan;Tang, Ailing;Liu, Yingliang;Guo, Qiang;Zhou, Erjun. And the article was included in Science China: Chemistry in 2020.Related Products of 148231-12-3 This article mentions the following:

Poly(3-hexylthiophene) (P3HT) is one of the most used semiconducting polymers for organic photovoltaics because it has potential for commercialization due to its easy synthesis and stability. Although the rapid development of the small mol. non-fullerene acceptors (NFAs) have largely improved the power conversion efficiency (PCE) of organic solar cells (OSCs) based on other complicated p-type polymers, the PCE of P3HT-based OSCs is still low. In addition, the design principle and structure-properties correlation for the NFAs matching well with P3HT are still unclear and need to be investigated in depth. Here we designed a series of NFAs comprised of acceptor (A) and donor (D) units with an A₂-A₁-D-A₁-A₂ configuration. These NFAs are abbreviated as Qx3, Qx3b and Qx3c, where indaceno[1,2-b:5,6-b’]dithiophene (IDT), quinoxaline (Qx) and 2-(1,1-dicyanomethylene)rhodanine serve as the middle D, bridged A₁ and the end group A₂, resp. By subtracting the Ph side groups appended on both IDT and Qx skeletons, the absorption spectra, energy levels and crystallinity could be regularly modulated. When paired with P3HT, three NFAs show totally different photovoltaic performance with PCEs of 3.37% (Qx3), 6.37% (Qx3b) and 0.03% (Qx3c), resp. From Qx3 to Qx3b, the removing of Ph side chain in the middle IDT unit results in the increase of crystallinity and electron mobility. However, after subtracting all the grafted Ph side groups on both IDT and Qx units, the final mol. Qx3c exhibits the lowest PCE of only 0.03%, which is mainly attributed to the serious phase-separation of the blend film. These results demonstrate that optimizing the substituted position of Ph side groups for A₂-A₁-D-A₁-A₂ type NFAs is vital to regulate the optoelectronic property of mol. and morphol. property of active layer for high performance P3HT-based OSCs. In the experiment, the researchers used many compounds, for example, 5,8-Dibromoquinoxaline (cas: 148231-12-3Related Products of 148231-12-3).

5,8-Dibromoquinoxaline (cas: 148231-12-3) 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 number of pyrazine-based derivatives were used as dyes or fluorescent probes.Related Products of 148231-12-3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

Hydrophobicity parameter of diazines IV: a new hydrogen-accepting parameter of monosubstituted (di)azines for the relationship of partition coefficients in different solvent systems was written by Yamagami, Chisako;Fujita, Toshio. And the article was included in Journal of Pharmaceutical Sciences in 2000.Name: Ethyl pyrazine-2-carboxylate This article mentions the following:

The authors recently proposed a new H-accepting scale, S_HA, for each member of the substituted (di)azine series from the heat of formation calculated under various dielec. environments by the COSMO method. The S_HA scale was used to examine relations between log P_CL (P_CL: CHCl₃/H₂O partition coefficient) and log P_oct (P_oct: 1-octanol/H₂O partition coefficient) for each of the 2-substituted pyridine (I), monosubstituted pyrazine (II), and pyrimidine (III) series. This S_HA parameter worked nicely, representing the H-accepting effect of the solute mol. A correlation equation with excellent quality, such as log P_CL = a log P_oct + sS_HA + constant, was obtained for each series. The authors further defined the parameter S_HA/PY, derived from S_HA values for the heterocyclic series by shifting the reference points to unsubstituted pyridine, to unify sep. derived correlation equations. Thus, the correlation between log P_CL and log P_oct for all combined data of three series was derived by using a single equation as log P_CL = a log P_oct + sS_HA/PY + constant The S_HA parameters were reasonably considered as being free-energy related, and the rationale for the H-bond-acceptor scale was presented. In the experiment, the researchers used many compounds, for example, Ethyl pyrazine-2-carboxylate (cas: 6924-68-1Name: Ethyl pyrazine-2-carboxylate).

Ethyl pyrazine-2-carboxylate (cas: 6924-68-1) 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. Substituted pyrazines have been found as subunits of multiple synthetically constructed therapeutic agents, as well as several natural products.Name: Ethyl pyrazine-2-carboxylate

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem

A Predictive Model Towards Site-Selective Metalations of Functionalized Heterocycles, Arenes, Olefins, and Alkanes using TMPZnCl·LiCl was written by Balkenhohl, Moritz;Jangra, Harish;Makarov, Ilya S.;Yang, Shu-Mei;Zipse, Hendrik;Knochel, Paul. And the article was included in Angewandte Chemie, International Edition in 2020.SDS of cas: 322-46-3 This article mentions the following:

The development of a predictive model towards site-selective deprotometalation reactions using TMPZnCl·LiCl is reported (TMP = 2,2,6,6-tetramethylpiperidinyl). The pK_a values of functionalized N-, S-, and O-heterocycles, arenes, alkenes, or alkanes were calculated and compared to the exptl. deprotonation sites. Large overlap (>80%) between the calculated and empirical deprotonation sites was observed, showing that thermodn. factors strongly govern the metalation regioselectivity. In the case of olefins, calculated frozen state energies of the deprotonated substrates allowed a more accurate prediction. Addnl., various new N-heterocycles were analyzed and the metalation regioselectivities rationalized using the predictive model. 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. Pyrazines are part of several biologically active polycyclic compounds; examples are quinoxalines, phenazines; and the bio-luminescent natural products pteridines, flavins, and their derivatives. 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

Polarographic reduction of the azines was written by Wiberg, Kenneth B.;Lewis, Thomas P.. And the article was included in Journal of the American Chemical Society in 1970.HPLC of Formula: 322-46-3 This article mentions the following:

The polarog. reduction of many azines is irreversible, with the initial anion radical undergoing rapid reaction to give other products. Cyclic voltammetry is able in most cases to effect reoxidation of the anion radical before it reacts further, and gives the reversible electrode potential. The observed energy differences between azine and radical anion are well correlated with the results of CNDO (complete neglect of differential overlap) and SCF π-electron calculations In the experiment, the researchers used many compounds, for example, Pyrido[2,3-b]pyrazine (cas: 322-46-3HPLC of Formula: 322-46-3).

Pyrido[2,3-b]pyrazine (cas: 322-46-3) belongs to pyrazine derivatives. Pyrazines are part of several biologically active polycyclic compounds; examples are quinoxalines, phenazines; and the bio-luminescent natural products pteridines, flavins, and their derivatives. Pyrazine-based skeletons were incorporated into agents targeting a range of ailments. Many derivatives were synthesized and evaluated as potential cancer treatments.HPLC of Formula: 322-46-3

Referemce:
Pyrazine – Wikipedia,
Pyrazine | C4H4N2 – PubChem