151860-15-0Relevant articles and documents
A general procedure for the one-pot preparation of polyfunctionalized nitrocyclopropanes
Ballini, Roberto,Fiorini, Dennis,Palmieri, Alessandro
, p. 1704 - 1706 (2003)
Nitrocyclopropane formation has been successfully carried out by reaction of bromonitromethane with electrophilic alkenes bearing two electron-withdrawing groups in the α- and β-positions, and in the presence of potassium carbonate as base. The method allows good yields and moderate to satisfactory diastereoselectivity with linear alkenes, while shows the complete formation of the exo-product with N-alkylmaleimides.
Discovery of 2-(6-{[(6-Fluoroquinolin-2-yl)methyl]amino}bicyclo[3.1.0]hex- 3-yl)- N -hydroxypyrimidine-5-carboxamide (CHR-3996), a class i selective orally active histone deacetylase inhibitor
Moffat, David,Patel, Sanjay,Day, Francesca,Belfield, Andrew,Donald, Alastair,Rowlands, Martin,Wibawa, Judata,Brotherton, Deborah,Stimson, Lindsay,Clark, Vanessa,Owen, Jo,Bawden, Lindsay,Box, Gary,Bone, Elisabeth,Mortenson, Paul,Hardcastle, Anthea,Van Meurs, Sandra,Eccles, Suzanne,Raynaud, Florence,Aherne, Wynne
experimental part, p. 8663 - 8678 (2011/03/19)
A novel series of HDAC inhibitors demonstrating class I subtype selectivity and good oral bioavailability is described. The compounds are potent enzyme inhibitors (IC50 values less than 100 nM), and improved activity in cell proliferation assays was achieved by modulation of polar surface area (PSA) through the introduction of novel linking groups. Employing oral pharmacokinetic studies in mice, comparing drug levels in spleen to plasma, we selected compounds that were tested for efficacy in human tumor xenograft studies based on their potential to distribute into tumor. One compound, 21r (CHR-3996), showed good oral activity in these models, including dose-related activity in a LoVo xenograft. In addition 21r showed good activity in combination with other anticancer agents in in vitro studies. On the basis of these results, 21r was nominated for clinical development.
Mechanisms of trovafloxacin hepatotoxicity: Studies of a model cyclopropylamine-containing system
Sun, Qin,Zhu, Ran,Foss Jr., Frank W.,Macdonald, Timothy L.
, p. 6682 - 6686 (2008/03/14)
The mechanism for the hepatotoxicity of trovafloxacin remains unresolved. Trovafloxacin contains a cyclopropylamine moiety which has a potential to be oxidized to reactive intermediate(s) although other putative elements may exist. In this study, a drug model of trovafloxacin containing the cyclopropylamine substructure was synthesized. Chemical oxidation of the drug model by K3Fe(CN)6 and NaClO revealed that both oxidants oxidize this drug model to a reactive α,β-unsaturated aldehyde, 11. The structure of 11 was fully elucidated by LC/MS/MS and NMR analysis. These results suggested that P450s with heme-iron center and myeloperoxidase generating hypochlorous acid in the presence of chloride ion are capable of bioactivating the cyclopropylamine moiety of trovafloxacin. This deleterious metabolism may lead to eventual hepatotoxicity.
