Design, synthesis and biological evaluation of novel 5-methyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives as potent potassium-competitive acid blockers.

With the aim to discover a novel potent potassium-competitive acid blocker (P-CAB) agent, a series of 5-methyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives were synthesized, and their H+/K+-ATPase inhibitory activities and inhibitory action on histamine-stimulated gastric acid secretion in rats were evaluated. Among the compounds synthesized, compound 3'-((3-(2-fluorophenyl)-5-methyl-5,6-dihydropyrrolo[3,4-c]pyrazol-2(4H)-yl)methyl)-[1,1'-biphenyl]-3-carboxamide not only exhibited potent H+/K+-ATPase inhibitory activity but olso showed potent inhibitory action in vivo on histamine-stimulated gastric acid secretion. In addition, the lead compound displayed favourable oral pharmacokinetic properties in rats, which was worthy of further study as a novel P-CAB agent.

Nedaplatin salvage chemotherapy for cervical cancer.

PURPOSE: This systematic analysis was conducted to evaluate the efficacy and safety of nedaplatin based salvage chemotherapy for treatment of patients with advanced cervical cancer. METHODS: Clinical studies evaluating the efficacy and safety of nedaplatin based regimens on response and safety for patients with cervical cancer were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. RESULTS: For nedaplatin based regimens, 5 clinical studies including 264 patients with advanced cervical cancer were considered eligible for inclusion. The analysis showed that, in all patients, pooled RR was 74.6% (197/264). Major adverse effects were leukopenia, thrombocytopenia and nausea/vomiting. No treatment related death occurred with nedaplatin based treatment. CONCLUSION: This systematic analysis suggests that nedaplatin based regimens are associated with good activity with acceptable tolerability in treating patients with advanced cervical cancer.