Orally active benzoxazole derivative as 5-HT3 receptor partial agonist for treatment of diarrhea-predominant irritable bowel syndrome.
During our search for therapeutic agents to treat diarrhea-predominant IBS, we found that 2-substituted benzoxazole derivatives have a characteristic 5-HT(3) receptor partial agonist activity with high affinity. Some of these compounds showed high in vitro metabolical stability, and 6g showed marked antidiarrhetic activity with little side effect of constipation in in vivo tests. Our results indicate that 5-HT(3) receptor partial agonists might be superior as therapeutic agents to the drugs currently used for IBS treatment.
Yoshida
Satoshi
S
Pharmaceutical Research Department, Meiji Seika Kaisha, Ltd., 760 Morooka-Cho, Kohoku-ku, Yokohama 222-8567, Japan. satoshi_yoshida@meiji.co.jp
Shiokawa
Sojiro
S
Kawano
Ken-ichi
K
Ito
Tomoko
T
Murakami
Hiroshi
H
Suzuki
Hisashi
H
Sato
Yasuo
Y
D000284:Administration, Oral; D000818:Animals; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000502:physiology; D003967:Diarrhea / Q000188:drug therapy*; D005772:Gastrointestinal Transit / Q000187:drug effects; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D058827:Serotonin 5-HT3 Receptor Agonists; D013329:Structure-Activity Relationship
C506295:5-chloro-7-methyl-2-(1-homopiperazinyl)benzoxazole; D001583:Benzoxazoles; D010879:Piperazines; D058827:Serotonin 5-HT3 Receptor Agonists