Pyrazole: preclinical reassessment

Abstract

Pyrazole (NSC-45410) is a low molecular weight, heterocyclic compound which has been considered for reevaluation in the clinic as a potential cytotoxic agent (Fig. 1). Discovered in 1893, pyrazole is best known as an inhibitor of liver alcohol dehydrogenase (ki = 0.2 uM), and as a result, has been used extensively in studies of alcohol metabolism. In 1960, pyrazole was identified as being active in preclinical antitumor models, which led to preliminary clinical testing. The early Phase I studies were not followed by disease specific Phase II trials, and the clinical activity of the drug has never been evaluated. This omission was noted by the National Cancer Institute's Project for the Review of Old Drugs (PROD), at which time it was also noted that pyrazole is selectively toxic to thyroid tissue in an animal model. Hence, interest in pyrazole was revived for two reasons: (a) failure to screen it for clinical activity in the 1960's, and (b) current interest in discovering drugs with selective toxicity to specific tissues for evaluation of their activity in malignancies arising in the target tissue. In this review, we summarize the evidence which has accumulated concerning pyrazole's potential role as an anticancer agent.

Induction of erythroid differentiation and modulation of gene expression by tiazofurin in K-562 leukemia cells.

“…NSC-286193) potently inhibits the proliferation ofa variety of experimental and human neoplasms and is now in phase I and II clinical trial (11,12 (20). As with the G reins, the normal c-ras proteins as with plasm membrane bind GTP and GDP and have GTlase activity (21,22).…”

Synthesis of pyranopyrazolo N-glycoside and pyrazolopyranopyrimidine C-glycoside derivatives as promising antitumor and antimicrobial agents

“…The reaction mixture was refl uxed for 2 h, concentrated, cooled, and the solid product that separated out was fi ltered off and recrystallized from appropriate solvent to give 10a,b. [4',3':5,6]pyrano [3,2-e] [1,2,4]triazolo [1,5-c]…”

“…For this reason, the discovery and development of new types of highly selective anticancer agents is still a very urgent topic. Pyrazolone nucleus has att racted much att ention due to its interesting biological activities (2)(3)(4)(5). The chemistry of pyrazole derivatives received great att ention because of their biological activities as potential HIV-1 inhibitors (6), insecticides, fungicides (7), antiviral agents (8) and anticancer activity (9).…”

Synthesis and Spectral Identification of Novel Stable Triazene: As Raw Material for the Synthesis Biocompatible Surfactants-Pyrazole-Isoxazole-Dihydropyrimidine-Tetrahydropyridine Derivatives

“…Simple nitrogen-containing heterocycles receive a large amount of attention in the literature, as a consequence of their exciting biological properties and their role as pharmacophores of considerable historical importance. Pyrazolones nucleus have attracted much attention due to their interesting biological activities [9] [10]. Pyrazolone derivatives are widely used in medical practice (antipyrine, amidopyrine, analgin, etc.)…”