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Development of novel, highly potent inhibitors of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF): increasing cellular potency through optimization of a distal heteroaromatic group.

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We describe the design, synthesis, and optimization of a series of new inhibitors of V-RAF murine sarcoma viral oncogene homologue B1 (BRAF), a kinase whose mutant form (V600E) is implicated in several types of cancer, with a particularly high frequency in melanoma. Our previously described

Novel tricyclic pyrazole BRAF inhibitors with imidazole or furan central scaffolds.

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V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) is a serine/threonine-specific protein kinase that is mutated with high frequency in cutaneous melanoma, and many other cancers. Inhibition of mutant BRAF is an attractive therapeutic approach for the treatment of melanoma. A triarylimidazole

Discovery and Optimization of Potent, Cell-Active Pyrazole-Based Inhibitors of Lactate Dehydrogenase (LDH).

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We report the discovery and medicinal chemistry optimization of a novel series of pyrazole-based inhibitors of human lactate dehydrogenase (LDH). Utilization of a quantitative high-throughput screening paradigm facilitated hit identification, while structure-based design and multiparameter

Synthesis and antitumor properties of pyrazolo [3,4-D] pyrimidine derivatives.

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Several new 5-substituted 1-phenylpyrazole [3,4-d] pyrimidine derivatives were synthesized and tested for antitumor activity. Compound 17, which has 3,4-dichlorophenyl moiety at N5 of the pyrazole pyrimidine ring, shows a strong activity against L-1210 leukemia (152%). On the other hand, compounds

Design and synthesis of novel amino-substituted xanthenones and benzo[b]xanthenones: evaluation of their antiproliferative activity and their ability to overcome multidrug resistance toward MES-SA/D x 5 cells.

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A number of new xanthenone and benzo[b]xanthenone amino derivatives and their pyrazole-fused counterparts have been designed and synthesized possessing structural analogy to the potent anticancer agent 9-methoxypyrazoloacridine. The synthesis of the compounds proceeds through nucleophilic

Anthrapyrazoles, a new class of intercalating agents with high-level, broad spectrum activity against murine tumors.

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A series of 5-[(aminoalkyl)amino]-substituted anthra[1,9-cd] pyrazol-6(2H)ones (anthrapyrazoles) were synthesized. These compounds, which differ from the anthracenediones in that an additional pyrazole ring has been fused to the anthracene system in place of one carbonyl group, were evaluated in

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