Li, Zhanhui’s team published research in European Journal of Medicinal Chemistry in 2020-11-01 | CAS: 100-70-9

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 100-70-9 belongs to class nitriles-buliding-blocks, name is Picolinonitrile, and the molecular formula is C6H4N2, COA of Formula: C6H4N2.

Li, Zhanhui published the artcileDesign, synthesis, and evaluation of pyrrolidine based CXCR4 antagonists with in vivo anti-tumor metastatic activity, COA of Formula: C6H4N2, the main research area is pyrrolidine preparation antitumor metastatic activity lipophilicity antagonist; Antagonist; CXCL12; CXCR4; Chemokine; GPCR.

The design, synthesis and evaluation of novel CXCR4 antagonists were based on a pyrrolidine scaffold e.g., 3-(1,3-dioxolan-2-yl)-1-(3-methylpyridin-2-yl)propan-1one. The structural exploration/optimization identified numerous potent CXCR4 antagonists, represented by (S)-2-methyl-4-(4-methylpiperazin-1-yl)-6-((2-(3methylpyridin-2-yl)pyrrolidin-1-yl)methyl)pyrimidine, which displayed potent binding affinity to CXCR4 receptor (IC50 = 79 nM competitively displacing fluorescent 12G5 antibody) and inhibited CXCL12 induced cytosolic calcium flux (IC50 = 0.25 nM). Moreover, in a transwell invasion assay, (S)-2-methyl-4-(4-methylpiperazin-1-yl)-6-((2-(3methylpyridin-2-yl)pyrrolidin-1-yl)methyl)pyrimidine significantly mitigated CXCL12/CXCR4 mediated cell migration. The (S)-2-Methyl-4-(4-methylpiperazin-1-yl)-6-((2-(3methylpyridin-2-yl)pyrrolidin-1-yl)methyl)pyrimidine exhibited good physicochem. properties (MW 367, logD7.4 1.12, pKa 8.2) and excellent in vitro safety profiles (e.g., hERG patch clamp IC50 > 30μM and minimal CYP isoenzyme inhibition). Importantly, (S)-2-methyl-4-(4-methylpiperazin-1-yl)-6-((2-(3methylpyridin-2-yl)pyrrolidin-1-yl)methyl)pyrimidine displayed much improved metabolic stability in human and rat liver microsomes. Lastly, (S)-2-Methyl-4-(4-methylpiperazin-1-yl)-6-((2-(3methylpyridin-2-yl)pyrrolidin-1-yl)methyl)pyrimidine demonstrated marked efficacy in a cancer metastasis model in mice. These results strongly support (S)-2-methyl-4-(4-methylpiperazin-1-yl)-6-((2-(3methylpyridin-2-yl)pyrrolidin-1-yl)methyl)pyrimidine as a prototypical lead for the development of promising CXCR4 antagonists as clin. candidates.

European Journal of Medicinal Chemistry published new progress about Antitumor agents. 100-70-9 belongs to class nitriles-buliding-blocks, name is Picolinonitrile, and the molecular formula is C6H4N2, COA of Formula: C6H4N2.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Boutard, Nicolas’s team published research in ChemMedChem in 2019 | CAS: 1885-29-6

ChemMedChem published new progress about Antitumor agents. 1885-29-6 belongs to class nitriles-buliding-blocks, name is 2-Aminobenzonitrile(Flakes or Chunks), and the molecular formula is C7H6N2, Application In Synthesis of 1885-29-6.

Boutard, Nicolas published the artcileDiscovery and structure-activity relationships of N-aryl 6-aminoquinoxalines as potent PFKFB3 kinase inhibitors, Application In Synthesis of 1885-29-6, the main research area is crystal structure neoplasm antitumor PFKFB3 kinase inhibitor aminoquinoxaline; cancer; enzymes; glycolysis; inhibitors; metabolism.

Energy and biomass production in cancer cells are largely supported by aerobic glycolysis in what is called the Warburg effect. The process is regulated by key enzymes, among which phosphofructokinase PFK-2 plays a significant role by producing fructose-2,6-biphosphate; the most potent activator of the glycolysis rate-limiting step performed by phosphofructokinase PFK-1. Herein, the synthesis, biol. evaluation and structure-activity relationship of novel inhibitors of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which is the ubiquitous and hypoxia-induced isoform of PFK-2, are reported. X-ray crystallog. and docking were instrumental in the design and optimization of a series of N-aryl 6-aminoquinoxalines. The most potent representative, N-(4-methanesulfonylpyridin-3-yl)-8-(3-methyl-1-benzothiophen-5-yl)quinoxalin-6-amine, displayed an IC50 of 14 nM for the target and an IC50 of 0.49 μM for fructose-2,6-biphosphate production in human colon carcinoma HCT116 cells. This work provides a new entry in the field of PFKFB3 inhibitors with potential for development in oncol.

ChemMedChem published new progress about Antitumor agents. 1885-29-6 belongs to class nitriles-buliding-blocks, name is 2-Aminobenzonitrile(Flakes or Chunks), and the molecular formula is C7H6N2, Application In Synthesis of 1885-29-6.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Lauria, Antonino’s team published research in Bioorganic & Medicinal Chemistry in 2005-03-01 | CAS: 59146-60-0

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 59146-60-0 belongs to class nitriles-buliding-blocks, name is 2-Amino-4-methyl-1H-pyrrole-3-carbonitrile, and the molecular formula is C6H7N3, Safety of 2-Amino-4-methyl-1H-pyrrole-3-carbonitrile.

Lauria, Antonino published the artcileAnnelated pyrrolo-pyrimidines from amino-cyanopyrroles and BMMAs as leads for new DNA-interactive ring systems, Safety of 2-Amino-4-methyl-1H-pyrrole-3-carbonitrile, the main research area is sulfanylmethyleneamino ester aminocyanopyrrole heterocyclization; pyrrolopyrimidine preparation anticancer; imidazopyrrolopyrimidine preparation anticancer.

The efficient one-pot synthesis of several tricyclic systems, e.g., I, obtained from the reaction of substituted 2-amino-3-cyanopyrroles and 3-amino-4-cyanopyrroles with BMMAs, is reported. The duration and yields of the reaction strongly depend on the reactivity of the starting pyrrole and on the size of the ring to be formed. Mechanist features of the reaction were investigated and proposed by studying also the reactivity of a 3-aminopyrrole-2,4-dicyano substituted. The method reported represents an example of the use of BMMA reagents in combination with pyrrole derivatives and allowed an easy and versatile entry to a large number of pyrrolo-pyrimidines further annelated with nitrogen heterocycles of different sizes. These polycondensed heterocycles possessed the requisite to interact with DNA.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 59146-60-0 belongs to class nitriles-buliding-blocks, name is 2-Amino-4-methyl-1H-pyrrole-3-carbonitrile, and the molecular formula is C6H7N3, Safety of 2-Amino-4-methyl-1H-pyrrole-3-carbonitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Zhang, Yaling’s team published research in Journal of Enzyme Inhibition and Medicinal Chemistry in 2019 | CAS: 1885-29-6

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Antitumor agents. 1885-29-6 belongs to class nitriles-buliding-blocks, name is 2-Aminobenzonitrile(Flakes or Chunks), and the molecular formula is C7H6N2, Safety of 2-Aminobenzonitrile(Flakes or Chunks).

Zhang, Yaling published the artcileNovel 4-arylaminoquinazolines bearing N,N-diethyl(aminoethyl)amino moiety with antitumor activity as EGFRwt-TK inhibitor, Safety of 2-Aminobenzonitrile(Flakes or Chunks), the main research area is arylaminoquinazoline synthesis antcancer EGFR apoptosis cell cycle cancer; -diethyl(aminoethyl)amino moiety; Quinazoline derivatives; antiproliferative activities; molecular docking; wild type epidermal growth factor receptor tyrosine kinase (EGFR-TK).

Herein, four novel 4-arylaminoquinazoline derivatives with N,N-diethyl(aminoethyl)amino moiety were designed, synthesized and evaluated on biol. activities in vitro. All synthesized compounds have inhibitory effects against tumor cells (SW480, A549, A431 and NCI-H1975). In particular, 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(5-((N,N-diethyl(aminoethyl))aminomethyl)furan-2-yl)quinazoline () and 6-(5-((N,N-diethylethyl)aminomethyl)furan-2-yl)-4-(4-(E)-(propen-1-yl)phenylamino)quinazoline () were potent antitumor agents which showed high antiproliferative activities against tumor cells in vitro. Moreover, compound could induce late apoptosis of A549 cells at high concentrations and arrest cell cycle of A549 cells in the G0/G1 phase at tested concentrations Also, compound could inhibit the activity of wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) with IC50 value of 15.60 nM. Mol. docking showed that compound formed three hydrogen bonds with EGFRwt-TK, while lapatinib formed only two hydrogen bonds with the receptor protein. It is believed that this work would be giving a reference for developing anti-cancer drugs targeted EGFR-TK.

Journal of Enzyme Inhibition and Medicinal Chemistry published new progress about Antitumor agents. 1885-29-6 belongs to class nitriles-buliding-blocks, name is 2-Aminobenzonitrile(Flakes or Chunks), and the molecular formula is C7H6N2, Safety of 2-Aminobenzonitrile(Flakes or Chunks).

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Zhuo, Liang’s team published research in European Journal of Organic Chemistry in 2021-06-21 | CAS: 100-70-9

European Journal of Organic Chemistry published new progress about Antitumor agents. 100-70-9 belongs to class nitriles-buliding-blocks, name is Picolinonitrile, and the molecular formula is C6H4N2, Product Details of C6H4N2.

Zhuo, Liang published the artcileAerobic Visible-Light Induced Intermolecular S-N Bond Construction: Synthesis of 1,2,4-Thiadiazoles from Thioamides under Photosensitizer-Free Conditions, Product Details of C6H4N2, the main research area is thiadiazole preparation green chem; thioamide photochem desulfurization oxidative cyclization.

Aerobic visible-light induced intermol. S-N bond construction has been achieved without the addition of photosensitizer, metal, or base. With this strategy, 1,2,4-thiadiazoles I (R = Ph, 4-methoxyphenyl, thiophen-3-yl, etc.; R1 = 4-methoxyphenyl, 2,6-dimethylphenyl, thiophen-2-yl, etc.) can be obtained from thioamides R/R1C(S)NH2. Preliminary mechanistic investigation suggested that the excited state of thioamides undergoes a single-electron-transfer (SET) process to afford thioamidyl radicals, which can be further transformed into a 1,2,4-thiadiazole through desulfurization and oxidative cyclization. The reaction has good functional group tolerance and represents a green method for the construction of S-N bonds.

European Journal of Organic Chemistry published new progress about Antitumor agents. 100-70-9 belongs to class nitriles-buliding-blocks, name is Picolinonitrile, and the molecular formula is C6H4N2, Product Details of C6H4N2.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Li, Xingshu’s team published research in Journal of the American Chemical Society in 2019-01-23 | CAS: 91-15-6

Journal of the American Chemical Society published new progress about Antitumor agents. 91-15-6 belongs to class nitriles-buliding-blocks, name is Phthalonitrile, and the molecular formula is C8H4N2, Computed Properties of 91-15-6.

Li, Xingshu published the artcileIn Vivo Albumin Traps Photosensitizer Monomers from Self-Assembled Phthalocyanine Nanovesicles: A Facile and Switchable Theranostic Approach, Computed Properties of 91-15-6, the main research area is albumin photosensitizer self assembly phthalocyanine nanovesicle switchable theranostic.

Albumin is a promising candidate as a biomarker for potential disease diagnostics and has been extensively used as a drug delivery carrier for decades. In these two directions, many albumin-detecting probes and exogenous albumin-based nanocomposite delivery systems have been developed. However, there are only a few cases demonstrating the specific interactions of exogenous probes with albumin in vivo, and nanocomposite delivery systems usually suffer from tedious fabrication processes and potential toxicity of the complexes. Herein, we demonstrate a facile “”one-for-all”” switchable nanotheranostic (NanoPcS) for both albumin detection and cancer treatment. In particular, the in vivo specific binding between albumin and PcS, arising from the disassembly of injected NanoPcS, is confirmed using an inducible transgenic mouse system. Fluorescence imaging and antitumor tests on different tumor models suggest that NanoPcS has superior tumor-targeting ability and the potential for time-modulated, activatable photodynamic therapy.

Journal of the American Chemical Society published new progress about Antitumor agents. 91-15-6 belongs to class nitriles-buliding-blocks, name is Phthalonitrile, and the molecular formula is C8H4N2, Computed Properties of 91-15-6.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Lelieveldt, Lianne P. W. M.’s team published research in Organic & Biomolecular Chemistry in 2019 | CAS: 100-70-9

Organic & Biomolecular Chemistry published new progress about Antitumor agents. 100-70-9 belongs to class nitriles-buliding-blocks, name is Picolinonitrile, and the molecular formula is C6H4N2, Safety of Picolinonitrile.

Lelieveldt, Lianne P. W. M. published the artcileVinylboronic acid-caged prodrug activation using click-to-release tetrazine ligation, Safety of Picolinonitrile, the main research area is vinylboronic acid cage prodrug click controlled release tetrazine ligation.

Bioorthogonal reactions can be performed selectively in the presence of any biol. functional group and are widely used to achieve site-selective chem. modifications of biomols. The click-to-release reaction is a bioorthogonal bond-cleavage variant that has gained much interest over the last few years. The bioorthogonal reaction between tetrazines and trans-cyclooctenes or vinyl ethers, for example, initiates the release of a small mol. immediately after the cycloaddition with tetrazines. Recently, our group reported that vinylboronic acids (VBAs) give exceptionally high reaction rates in the bioorthogonal inverse electron-demand Diels-Alder reaction with tetrazines that are substituted with boron-coordinating ligands. In the present study, we show that VBAs can be used in a click-to-release variant and demonstrate its bioorthogonality with a VBA-protected doxorubicin prodrug. We show that the cytotoxicity of doxorubicin is silenced by the attachment of the VBA, and activity can be largely restored upon the reaction with a tetrazine, inducing cell death.

Organic & Biomolecular Chemistry published new progress about Antitumor agents. 100-70-9 belongs to class nitriles-buliding-blocks, name is Picolinonitrile, and the molecular formula is C6H4N2, Safety of Picolinonitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Uruma, Yoshiyuki’s team published research in Bioorganic & Medicinal Chemistry in 2019-08-01 | CAS: 91-15-6

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 91-15-6 belongs to class nitriles-buliding-blocks, name is Phthalonitrile, and the molecular formula is C8H4N2, Synthetic Route of 91-15-6.

Uruma, Yoshiyuki published the artcileSynthesis and biological evaluation of glucose conjugated phthalocyanine as a second-generation photosensitizer, Synthetic Route of 91-15-6, the main research area is glucose conjugated phthalocyanine preparation PDT photosensitizer cancer; Glucose; Hypoxia; Near-infrared (NIR) irradiation; Photodynamic therapy (PDT); Photosensitizers (PSs); Phthalocyanine (Pc).

Photodynamic therapy (PDT) is a treatment method using light and photosensitizers (PSs), which is categorized as a non-invasive surgery treatment for cancers. When the tumor is exposed to a specific light, the PSs become active and generate reactive oxygen species (ROS), mainly singlet oxygen which kills nearby cancer cells. PDT is becoming more widely recognized as a valuable treatment option for localized cancers and pre-cancers of skin as it has no long-term effects on the patient. But, due to the limited penetration rate of light into the skin and other organs, PDT can’t be used to treat large cancer cells or cancer cells that have grown deeply into the skin or other organs. Hence, in this study, our focus centers on synthesizing glucose-conjugated phthalocyanine (Pc) compatible with near-IR (NIR) irradiation as second-generation photosensitizer, so that PDT can be used in a wider range to treat cancers without obstacles.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 91-15-6 belongs to class nitriles-buliding-blocks, name is Phthalonitrile, and the molecular formula is C8H4N2, Synthetic Route of 91-15-6.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Xu, Yiming’s team published research in Bioorganic & Medicinal Chemistry in 2020-02-15 | CAS: 1885-29-6

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 1885-29-6 belongs to class nitriles-buliding-blocks, name is 2-Aminobenzonitrile(Flakes or Chunks), and the molecular formula is C7H6N2, Formula: C7H6N2.

Xu, Yiming published the artcileNew modification strategy of matrine as Hsp90 inhibitors based on its specific L conformation for cancer treatment, Formula: C7H6N2, the main research area is radicicol thermal shift assay anticancer activity mechanism of action; Anticancer activity; L-shaped matrine derivatives; Mechanism of action; Radicicol; Thermal shift assay.

The similarity of spatial structure between radicicol and matrine urged us to perform conformation modification of matrine, followed by L-shaped matrine derivatives, 6, 12, 21a-h and 22a-h were originally designed, synthesized and evaluated for Hsp90N inhibitors as anticancer agents. TSA (Thermal Shift Assay) results indicated that 21e, 22a-c and 22e-g exhibited strong binding force against Hsp90N with|ΔTm| > 3, meanwhile, MTT assay also revealed these compounds displayed potent anticancer activity with IC50 values below 25μM against HepG2, HeLa and MDA-MB-231 cells lines. Then, compound 22g with a high ΔTm = 10.92 was chosen as a representative to perform further mechanism study. It can induce cell apoptosis, arrest the cell cycle at the S phase and decrease the expression level of Hsp90 in Hela cell. These results originally provided targeted modification strategy for matrine derivatives to serve as Hsp90 inhibitors for cancer therapy.

Bioorganic & Medicinal Chemistry published new progress about Antitumor agents. 1885-29-6 belongs to class nitriles-buliding-blocks, name is 2-Aminobenzonitrile(Flakes or Chunks), and the molecular formula is C7H6N2, Formula: C7H6N2.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts

Zheng, Ke’s team published research in ACS Applied Materials & Interfaces in 2021-03-10 | CAS: 91-15-6

ACS Applied Materials & Interfaces published new progress about Antitumor agents. 91-15-6 belongs to class nitriles-buliding-blocks, name is Phthalonitrile, and the molecular formula is C8H4N2, Application of Phthalonitrile.

Zheng, Ke published the artcileNovel pH-Triggered Doxorubicin-Releasing Nanoparticles Self-Assembled by Functionalized β-Cyclodextrin and Amphiphilic Phthalocyanine for Anticancer Therapy, Application of Phthalonitrile, the main research area is cyclodextrin nanotheranostic pH sensitive release combination therapy phthalocyanine; combination therapy; cyclodextrin; nanotheranostics; pH-sensitive release; phthalocyanine.

Cyclodextrins (CDs), as pharmaceutical excipients with excellent biocompatibility, non-immunogenicity, and low toxicity in vivo, are widely used to carry drugs by forming inclusion complexes for improving the solubility and stability of drugs. However, the limited space of CDsâ€?lipophilic central cavity affects the loading of many drugs, especially with larger mols. In this study, β-CDs were modified by acetonization to improve the affinity for the chemotherapy drug doxorubicin (DOX), and doxorubicin-adsorbing acetalated β-CDs (Ac-CD:DOX) self-assembled to nanoparticles, followed by coating with the amphiphilic zinc phthalocyanine photosensitizer ZnPc-(PEG)5 for antitumor therapy. The final product ZnPc-(PEG)5:Ac-CD:DOX was demonstrated to have excellent stability and pH-sensitive drug release characteristics. The cell viability and apoptosis assay showed synergistic cytotoxic effects of chemotherapy and phototherapy. The mechanism of cytotoxicity was analyzed in terms of intracellular reactive oxygen species, mitochondrial membrane potential, and subcellular localization. More importantly, in vivo experiments indicated that ZnPc-(PEG)5:Ac-CD:DOX possessed significant tumor targeting, prominent antitumor activity, and less side effects. Our strategy expands the application of CDs as drug carriers and provides new insights into the development of CD chem.

ACS Applied Materials & Interfaces published new progress about Antitumor agents. 91-15-6 belongs to class nitriles-buliding-blocks, name is Phthalonitrile, and the molecular formula is C8H4N2, Application of Phthalonitrile.

Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts