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Página 1 a partir de 119 resultados
Synthesis of 2-(allylthio)pyrazines as a novel cancer chemopreventive agent.
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2-(Allylthio)pyrazine derivatives were designed as a novel cancer chemopreventive agent that functions through selective inhibtion of cytochrome P-450 and induction of phase II enzymes involved in the detoxification of carcinogens. A practical preparation method of 2-(allylthio) pyrazine derivatives
Synthesis, chemical stability and pre-clinical anti-tumor activity of pyrazine diazohydroxide, sodium salt (NSC-361456).
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The synthesis, chemical stability and anti-tumor activity of pyrazine diazohydroxide, sodium salt, a compound that has been selected for development to clinical trials, are described. The compound shows a half-life of about 100 minutes at pH 7.4 and is active against a number of experimental tumors.
Phase II study of pyrazine diazohydroxide (NSC 361456) for advanced non small-cell lung cancer.
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Pyrazine diazohydroxide (NSC 361456) (PZDH) was selected for further development after demonstrating more stability than its parent compound and significant antitumor activity in a number of in vivo tumor models. Its proposed mechanism of action is through the formation of DNA adducts via the
Expansion of chemical space based on a pyrrolo[1,2-a]pyrazine core: Synthesis and its anticancer activity in prostate cancer and breast cancer cells.
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In connection with our continued research to generate new aza-fused heteroaromatic chemical scaffolds, we developed a highly atom-economical three-component route to novel 3,4-dihydropyrrolo[1,2-a]pyrazine ring skeleton multi-functionalized on the pyrazine unit. This [4+1+1] annulation approach led
Phase II trial of pyrazine diazohydroxide in androgen-independent prostate cancer.
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No effective therapy has been demonstrated for hormone refractory prostate cancer (HRPC). Pyrazine diazohydroxide (PZDH) is a novel antineoplastic agent with a broad range of activity in preclinical studies and a moderate toxicity profile in Phase I trials. We undertook a Phase II study of PZDH in
Phase II and pharmacodynamic studies of pyrazine diazohydroxide (NSC 361456) in patients with advanced renal and colorectal cancer.
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Pyrazine diazohydroxide (PZDH) is a novel antitumor agent that forms DNA adducts via the reactive pyrazine diazonium ion. In a recent Phase I study of PZDH, we identified a recommended Phase II dose of 100 mg/m2/day x 5, given as a 5-min i.v. bolus with the cycles repeated every 42 days (N. J.
2-Pyrazine-PPD, a Novel Dammarane Derivative, Showed Anticancer Activity by Reactive Oxygen Species-Mediate Apoptosis and Endoplasmic Reticulum Stress in Gastric Cancer Cells
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20 (R)-Dammarane-3β, 12β, 20, 25-tetrol (25-OH-PPD), a ginsenoside, was derived from Panax ginseng (C. A. Meyer) and inhibited growth of several cancer cell lines. To improve the anti-cancer activity, we introduced the pyrazine ring to 25-OH-PPD and obtained the compound
Phase I evaluation and pharmacokinetic study of pyrazine-2-diazohydroxide administered as a single bolus intravenous injection in patients with advanced solid tumors.
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The sodium salt of pyrazine-2-diazohydroxide (PZDH; NSC 361456) was identified as an active congener of the antitumor lead pyridine-2-diazotate with enhanced chemical stability under physiological conditions. In a phase I trial of PZDH administered as a single i.v. bolus injection, 19 patients with
Catalyst-Free One-Pot Synthesis of Densely Substituted Pyrazole-Pyrazines as Anti-Colorectal Cancer Agents
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The first catalyst-free post-Ugi cascade methodology was developed for expeditious access to structurally diverse and complex pyrazole-pyrazines in one-pot. This novel cascade reaction features an intramolecular N2-arylation of pyrazoles with allenes at the C-β position of triple bond. Screening in
Alternative splicing in human cancer cells is modulated by the amiloride derivative 3,5-diamino-6-chloro-N-(N-(2,6-dichlorobenzoyl)carbamimidoyl)pyrazine-2-carboxide.
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Alternative splicing (AS) is a process that enables the generation of multiple protein isoforms with different biological properties from a single mRNA. Cancer cells often use the maneuverability conferred by AS to produce proteins that contribute to growth and survival. In our previous studies, we
2-(Allylthio)pyrazine, a cancer chemopreventive agent, inhibits liver fibrosis induced by dimethylnitrosamine in rats: role of inhibition of transforming growth factor-beta1 expression.
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Exposure to nitrosamines may be the occupational risk factor for liver cirrhosis. 2-(Allylthio)pyrazine, a chemopreventive agent, inhibits CYP2E1 and induces phase II enzymes. We examined the effects of 2-(allylthio)pyrazine on hepatic fibrosis, a prepathologic state of cirrhosis, and on the
Discovery of (S)-1-(1-(Imidazo[1,2-a]pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-[1,2,3]triazolo[4,5-b]pyrazine (volitinib) as a highly potent and selective mesenchymal-epithelial transition factor (c-Met) inhibitor in clinical development for treatment of cancer.
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HGF/c-Met signaling has been implicated in human cancers. Herein we describe the invention of a series of novel triazolopyrazine c-Met inhibitors. The structure-activity relationship of these compounds was investigated, leading to the identification of compound 28, which demonstrated favorable
Pyrazine ring-based Na+/H+ exchanger (NHE) inhibitors potently inhibit cancer cell growth in 3D culture, independent of NHE1.
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The Na+/H+ exchanger-1 (NHE1) supports tumour growth, making NHE1 inhibitors of interest in anticancer therapy, yet their molecular effects are incompletely characterized. Here, we demonstrate that widely used pyrazinoylguanidine-type NHE1 inhibitors potently inhibit growth and
Production of reactive oxygen and nitrogen species by light irradiation of a nitrosyl phthalocyanine ruthenium complex as a strategy for cancer treatment.
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Production of reactive oxygen species has been used in clinical therapy for cancer treatment in a technique known as Photodynamic Therapy (PDT). The success of this therapy depends on oxygen concentration since hypoxia limits the formation of reactive oxygen species with consequent clinical failure
Dregamine and tabernaemontanine derivatives as ABCB1 modulators on resistant cancer cells.
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Dregamine (1) and tabernaemontanine (2), two epimeric monoterpene indole alkaloids isolated in large amount from the roots of the African plant Tabernaemontana elegans, were derivatized, yielding ten imine derivatives, as previously described (3-12). In the present study, aiming at increasing the
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