124473-12-7Relevant articles and documents
Structure-activity relationship of 2-[[(2-Pyridyl)methyl]thio]-1H- benzimidazoles as anti Helicobacter pylori agents in vitro and evaluation of their in vivo efficacy
Kühler, Thomas C.,Swanson, Marianne,Shcherbuchin, Vladimir,Larsson, H?kan,Mellg?rd, Bj?rn,Sj?str?m, Jan-Eric
, p. 1777 - 1788 (2007/10/03)
A relationship between the structure of 21 2-[[(2-pyridyl)methyl]thio]- 1H-benzimidazoles (6) and their anti Helicobacter pylori activity expressed as minimum bactericidal concentration (MBC) values is described. Observed MBCs ranged from 256 to 1 μg/mL. The structure - activity relationship (SAR) showed that larger and more lipophilic compounds, especially compounds with such substituents in the 4-position of the pyridyl moiety, generally had lower MBC values. Four new compounds 'that were predicted to be potent by the established SAR model were synthesized and tested. One such compound, i.e., 2-[[(4-[(cyclopropylmethyl)oxy]3-methyl-2-pyridyl)methyl]thio]-1H- benzimidazole (18), was tested for in vivo efficacy in a mouse Helicobacter felis model (125 μmol/kg bid given orally for 4 days, n = 4). Unfortunately, antibacterial activity could not be clearly demonstrated in this model. Instead a potent acid secretion inhibition was observed. This finding was attributed to the methylthio compound being oxidized to the corresponding methyl sulfinyl derivative, i.e., a proton pump inhibitor, in vivo. Although the antibacterial activity had the potential of decreasing H. felis cell counts in vivo the proton pump inhibitory effect became dominant and actually promoted H. felis cell growth. Hence, we conclude that the antibacterial utility of the 2-[[(2-pyridyl)methyl]thio]1H-benzimidazoles (6) as a compound class is compromised by their propensity to become proton pump inhibitors upon metabolic oxidation in vivo.
4(3H)-quinazolinone derivatives and pharmaceutical compositions
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, (2008/06/13)
4(3H)-Quinazolinone derivatives of formula (I) are provided. STR1 wherein R1 is a hydrogen atom, a C1 -C6 alkyl group, an aryl group, a substituted aryl group, or an aralkyl group; R2 is a C1 -C6 alkylamino group, a phenyl group, a substituted phenyl group, or a 5- or 6-membered heterocyclic group containing one or more N, O or S as a hetero atom or atoms, said heterocyclic group optionally being substituted or fused with a benzene ring; n is 1 or 2; or R2 represents a geranyl group or a dipyridylmethyl group together with the group --(CH2)n --; and X is a hydrogen atom, a C1 -C6 alkyl group or a halogen atom, and pharmaceutically acceptable acid addition salts thereof. They are useful as antiulcer agents.