Studies on anti-ulcer agents. II. Synthesis and anti-ulcer activities of 6-isopropylazulene-1-sodium sulfonate derivatives.
A series of alkylazulene-1-sodium sulfonate derivatives which has an isopropyl group at 6-position were synthesized, and their anti-ulcer activities were examined in Shay pylorus-ligated rats. The values of lipophilicity (log P) as a parameter of these new azulene derivatives were also examined in reference to the structure-activity relationship. The optimum value of log P, which showed maximal anti-ulcer activity, was about -0.46. Among the derivatives of azulene examined, 3-ethyl-6-isopropylazulene-1-sodium sulfonate (compound IXb:XT1-785) exhibited the most potent inhibitory action against Shay ulcer, and its anti-peptic activity was similar to that of 3-ethyl-7-isopropylazulene-1-sodium sulfonate (KT1-32). It also had more activity than guaiazulene sodium sulfonate (GAS). Furthermore, KT1-785 was extremely stable under heating as compared to GAS.
Yanagisawa
T
T
Kotobuki Seiyaku Co., Ltd. Nagano, Japan.
Kosakai
K
K
Tomiyama
T
T
Yasunami
M
M
Takase
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis*; D001190:Arylsulfonates / Q000138:chemical synthesis* / Q000494:pharmacology; D003508:Cycloheptanes / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D010434:Pepsin A / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000897:Anti-Ulcer Agents; D001190:Arylsulfonates; D003508:Cycloheptanes; D010434:Pepsin A