17797-10-3Relevant articles and documents
Optimization of N-benzyl-5-nitrofuran-2-carboxamide as an antitubercular agent
Gallardo-Macias, Ricardo,Kumar, Pradeep,Jaskowski, Mark,Richmann, Todd,Shrestha, Riju,Russo, Riccardo,Singleton, Eric,Zimmerman, Matthew D.,Ho, Hsin Pin,Dartois, Véronique,Connell, Nancy,Alland, David,Freundlich, Joel S.
supporting information, p. 601 - 606 (2019/01/04)
The optimization campaign for a nitrofuran antitubercular hit (N-benzyl-5-nitrofuran-2-carboxamide; JSF-3449) led to the design, synthesis, and biological profiling of a family of analogs. These compounds exhibited potent in vitro antitubercular activity (MIC = 0.019–0.20 μM) against the Mycobacterium tuberculosis H37Rv strain and low in vitro cytotoxicity (CC50 = 40–>120 μM) towards Vero cells. Significant improvements in mouse liver microsomal stability and mouse pharmacokinetic profile were realized by introduction of an α α-dimethylbenzyl moiety. Among these compounds, JSF-4088 is highlighted due to its in vitro antitubercular potency (MIC = 0.019 μM) and Vero cell cytotoxicity (CC50 > 120 μM). The findings suggest a rationale for the continued evolution of this promising series of antitubercular small molecules.
Evidence for significant through-space and through-bond electronic coupling in the 1,4-diphenylcyclohexane-1,4-diyl radical cation gained by absorption spectroscopy and DFT calculations
Ikeda, Hiroshi,Hoshi, Yosuke,Namai, Hayato,Tanaka, Futoshi,Goodman, Joshua L.,Mizuno, Kazuhiko
, p. 9207 - 9215 (2008/12/21)
Photoinduced single-electron-transfer promoted oxidation of 2,5-diphenyl-l,5-hexadiene by using N-methylquinolinium tetrafluoroborate/ biphenyl co-sensitization takes place with the formation of an intense electronic absorption band at 476 nm, which is attributed to the 1,4-diphenylcyclohexane-1,4-diyl radical cation. The absorption maximum (λob) of this transient occurs at a longer wavelength than is expected for either the cumyl radical or the cumyl cation components. Substitution at the para positions of the phenyl groups in this radical cation by CH3O, CH3, F, Cl, and Br leads to an increasingly larger redshift of λob. A comparison of the ρ value, which was obtained from a Hammett plot of the electronic transition energies of the radical cations versus σ+, with that for the cumyl cation shows that the substituent effects on the transition energies for the 1,4-diarylcyclohexane-1,4-diyl radical cations are approximately one half of the substituent effects on the transition energies of the cumyl cation. The observed substitu_ent-induced redshifts of λob and the reduced sensitivity of λob to substituent changes are in accordance with the proposal that significant through-space and -bond electronic interactions exist between the cumyl radical and the cumyl cation moieties of the 1,4-diphenylcyclohexane-1,4-diyl radical cation. This proposal gains strong support from the results of density functional theory (DFT) calculations. Moreover, the results of time-dependent DFT calculations indicate that the absorption band at 476 nm for the 1,4-diphenylcyclohexane-1,4-diyl radical cation corresponds to a SOMO-3-SOMO transition.
Heterosubstituted pyridine derivatives as PDE4 inhibitors
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, (2008/06/13)
The invention encompasses the novel compound of Formula I useful in the treatment of diseases, including asthma, by raising the level of cyclic adenosine-3′,5′-monophosphate (cAMP) through the inhibition of phosphodiesterase IV (PDE 4). or a pharmaceutically acceptable salt or hydrate thereof. The invention also encompasses pharmaceutical compositions and methods for treatment.
