Anti-Helicobacter pylori agents. 1. 2-(Alkylguanidino)-4-furylthiazoles and related compounds.
A series of 2-(alkylguanidino)-4-[5-(acetamidomethyl)furan-2-yl]thiazoles and related compounds were synthesized and evaluated for antimicrobial activity against Helicobacter pylori, inhibitory effect on gastric acid secretion, and histamine H2-receptor antagonist activity. Introduction of alkyl substituents on the guanidino moiety resulted in a significant increase in antimicrobial activity, which was associated with the alkyl chain length. Of the compounds obtained, the n-hexylguanidino derivative 13 demonstrated a 250-fold improvement in activity (MIC = 0.11 micrograms/mL) over the unsubstituted guanidino derivative 7. Alkyl-substituted guanidino derivatives also displayed gastric antisecretion and H2-antagonist activities. However, a simple correlation between the alkyl chain length and the activities was not found in these assays. Replacement of the guanidine with other bioisosteric groups (thiourea, urea, or (dimethylamino)methyl) resulted in loss of all activities tested. Thus the guanidino moiety was found to be essential for activity in this series of compounds.
Katsura
Y
Y
New Drug Research Laboratories, Fujisawa Pharmaceutical Company, Ltd., Osaka, Japan.
Tomishi
T
T
Inoue
Y
Y
Sakane
K
K
Matsumoto
Y
Y
Ishikawa
H
H
Takasugi
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D005744:Gastric Acid / Q000378:metabolism; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects*; D006635:Histamine H2 Antagonists / Q000138:chemical synthesis* / Q000627:therapeutic use; D008297:Male; D008826:Microbial Sensitivity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D011970:Receptors, Histamine H2 / Q000378:metabolism*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D006635:Histamine H2 Antagonists; D011970:Receptors, Histamine H2