18436-76-5Relevant articles and documents
Structure-activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods
Nsumiwa, Samkele,Kuter, David,Wittlin, Sergio,Chibale, Kelly,Egan, Timothy J.
, p. 3738 - 3748 (2013/07/19)
In order to probe structure-activity relationships of association with ferriprotoporphyrin IX (log K) and inhibition of β-hematin formation, a series of 4-aminoquinolines with varying substituents at the 7-position (X) have been synthesized. These have been further elaborated by introduction of two different R groups on the 4-amino nitrogen atom in the form of methyl (R = Me) and ethylamine (R = EtNH2) side chains. Data for a previously investigated series containing an N,N-diethyl-ethylamine side chain were also compared with the findings of this study. Experimentally, log K values for the simple 4-aminoquinoline series (R = H) were found to correlate with the hydrophobicity constant (π) of the group X. The log K values for the series with R = Me and EtNH2 were found to correlate with those of the series with R = H. The log of the 50% β-hematin inhibitory activity (log BHIA50) was found to correlate with log K and either meta (σm) or para (σp) Hammett constants for the series with R = Me and EtNH2, but not the simple series with R = H. To further improve predictability, correlations with ab initio electrostatic parameters, namely Mulliken and CHelpG charges were investigated. The best correlations were found with CHelpG charges which indicated that log K values can be predicted from the charges on atom H-8 and the group X in the quinolinium species computed in vacuum, while log BHIA50 values can be predicted from the CHelpG charges on C-7, C-8 and N-1 for the neutral species in vacuum. These correlations indicate that association and inhibition of β-hematin formation are separately determined. They also suggest that electron withdrawing groups at the 7-position, but not necessarily hydrophobic groups are required for hemozoin inhibition. The upshot is that the correlations imply that considerably more hydrophilic hemozoin inhibitors are feasible.
NITRO AND AMINO SUBSTITUTED TOPOISOMERASE AGENTS
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Page 21, (2010/02/06)
The invention provides compounds of formula 1 : wherein R1-R9, W, and X have any of the meanings defined in the specification and their pharmaceutically acceptable salts. The invention also provides pharmaceutical compositions comprising a compound of formula 1, processes for preparing compounds of formula 1, intermediates useful for preparing compounds of formula 1, and therapeutic methods for treating cancer using compounds of formula 1.
Thioquinolone compounds which have useful pharmaceutical activity
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, (2008/06/13)
Disclosed is a thioquinolone derivative which exhibits highly selective antibacterial activity against Helicobacter pylori.
