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8-Amino-3-benzyl-1,2,4-triazolo[4,3-a]pyrazines. Synthesis and anticonvulsant activity.
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Eleven substituted 8-amino-3-benzyl-1,2,4-triazolo[4,3-a] pyrazines were synthesized and tested for anticonvulsant activity against maximal electroshock-induced seizures (MES) in rats. The compounds were prepared in four stages from the phenylacetonitriles. I. The intermediate
Pyrazine diazohydroxide (NSC-361456). Phase I clinical and pharmacokinetic studies.
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Pyrazine diazohydroxide (NSC-361456) was identified as an active congener of pyridine 2-diazohydroxide with enhanced stability under physiologic conditions. In this phase I study, 35 patients with advanced cancer received 62 courses of PZDH administered intravenously every 3 weeks at doses ranging
A phase II trial of pyrazine diazohydroxide in patients with disseminated malignant melanoma and no prior chemotherapy--Southwest Oncology Group study.
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Malignant melanoma is rapidly increasing in the United States. Metastatic disease responds poorly to currently available chemotherapy. Pyrazine diazohydroxide (PZDH) is a new agent inhibiting DNA synthesis that is active in mouse tumor models and human xenografts and lacks cross resistance with
Phase I and pharmacokinetic study of a new antineoplastic agent: pyrazine diazohydroxide (NSC 361456).
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Pyrazine diazohydroxide (PZDH) is a novel antineoplastic agent that appears to form DNA adducts via the reactive pyrazine diazonium ion and produces substantial antitumor activity in preclinical models. We conducted a phase I trial to determine the maximally tolerated dose of PZDH that could be
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
Anorexigenic and ancillary actions of MK-212 (6-chloro-2-(1-piperazinyl)-pyrazine; CPP).
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In rats allowed to eat for 2 h/day and injected i.p. 30 min before feeding, MK-212, ED50 = 1.5 mg/kg, was two times more potent as an anorexigen than fenfluramine. However, the compounds were equiactive in the rat following p.o. administration 1.5 or 3 h before the test, while fenfluramine was more
Interaction of S 21007 with 5-HT3 receptors. In vitro and in vivo characterization.
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The interaction of S 21007 [5-(4-benzyl piperazin-1-yl)4H pyrrolo [1,2-a]thieno[3,2-e]pyrazine] with serotonin 5-HT3 receptors was investigated using biochemical, electrophysiological and functional assays. Binding studies using membranes from N1E-115 neuroblastoma cells showed that S 21007 is a
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