Anti-Helicobacter pylori Agents. 5. 2-(Substituted guanidino)-4-arylthiazoles and Aryloxazole Analogues

• Published in: Journal of medicinal chemistry Vol. 45; no. 1; pp. 143 - 150
• Main Authors: KATSURA, Yousuke, NISHINO, Shigetaka, INOUE, Yoshikazu, SAKANE, Kazuo, MATSUMOTO, Yoshimi, MORINAGA, Chizu, ISHIKAWA, Hirohumi, TAKASUGI, Hisashi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 03.01.2002; Amer Chemical Soc
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Chemistry, Medicinal; Colony Count, Microbial; Gastric Juice - metabolism; Guanidines - chemical synthesis; Guanidines - chemistry; Guanidines - pharmacology; Guinea Pigs; Helicobacter pylori - drug effects; Histamine H2 Antagonists - chemical synthesis; Histamine H2 Antagonists - chemistry; Histamine H2 Antagonists - pharmacology; In Vitro Techniques; Life Sciences & Biomedicine; Male; Medical sciences; Microbial Sensitivity Tests; Myocardium - metabolism; Oxazoles - chemical synthesis; Oxazoles - chemistry; Oxazoles - pharmacology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Rats; Science & Technology; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Thiophenes - chemical synthesis; Thiophenes - chemistry; Thiophenes - pharmacology; INFECTION; THERAPY; ANTAGONISTS; DERIVATIVES; PEPTIC-ULCER DISEASE; ANTIULCER DRUGS; Heart; Five membered ring; Intravenous administration; Rat; Nitrogen heterocycle; Spirillaceae; Antiulcer agent; Selectivity; Antihistaminic; Pyridine derivatives; Guinea pig; Helicobacter pylori; Structure activity relation; Antisecretory agent; Bacteria; Antagonist; Chemical synthesis; Oxazole derivatives; Oxygen nitrogen heterocycle; Sulfur nitrogen heterocycle; Spirillales; Rodentia; Benzene derivatives; Guanidines; In vitro; In vivo; Vertebrata; Mammalia; Animal; Affinity; Antibacterial agent; H2 Histamine receptor
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm010217j

To extend the SAR study of guanidinothiazoles as a structurally novel class of anti-H. pylori agents, a series of 2-(substituted guanidino)-4-arylthiazoles and some 4-aryloxazole analogues were synthesized and evaluated for antimicrobial activity against H. pylori, Some of them were also subjected to H2 antagonist and gastric antisecretory assays. Several arylthiazoles were identified as potent anti-H. pylori agents, and of these, thienylthiazole derivative 44 exhibited the strongest activity (MIC = 0.0065 mug/mL) among the compounds obtained in our guanidinothiazole studies. Although 44 was void of H2 antagonist activity, pyridylthiazole derivative 39 had both potent anti-H. pylori and H2 antagonist activities. Thiazolylthiazole derivative 46 also showed potent anti-H. pylori activity, but the H2 antagonist activity was weak. On the other hand, no attractive activities were found in pyrimidyl, oxazolyl, isoxazolyl, imidazolyl, and oxadiazolylthiazole derivatives. The anti-H. pylori activity of the aryloxazole analogues was weaker than those of the corresponding arylthiazole derivatives, though they had potent H2 antagonist activity.