Anti-Helicobacter pylori agents. 5. 2-(Substituted guanidino)-4-arylthiazoles and aryloxazole analogues.
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 microg/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.
Katsura
Yousuke
Y
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Company Ltd., 2-1-6, Kashima, Yodogawa-ku, Osaka 532-8514, Japan. yousuke_katsura@po.fujisawa.co.jp
Nishino
Shigetaka
S
Inoue
Yoshikazu
Y
Sakane
Kazuo
K
Matsumoto
Yoshimi
Y
Morinaga
Chizu
C
Ishikawa
Hirohumi
H
Takasugi
Hisashi
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015169:Colony Count, Microbial; D005750:Gastric Juice / Q000378:metabolism; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D016480:Helicobacter pylori / Q000187:drug effects*; D006635:Histamine H2 Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008826:Microbial Sensitivity Tests; D009206:Myocardium / Q000378:metabolism; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C444339:4-(3-acetamidomethyl)phenyl-2-(2-(2-(2-methoxyphenyl)ethyl)guanidino)thienylthiazole; D000900:Anti-Bacterial Agents; D006146:Guanidines; D006635:Histamine H2 Antagonists; D010080:Oxazoles; D013844:Thiazoles; D013876:Thiophenes