159026-17-2Relevant academic research and scientific papers
Basic studies on 5-(7-hydroxy-3-O-phosphonocholyl)aminosalicylic acid for the evaluation of microbial overgrowth
Konishi, Toshio,Takahashi, Makoto,Ohta, Shunsaku
, p. 370 - 375 (1997)
A newly synthesized conjugate of 7-hydroxy-3-O-phosphonocholic acid (ursodeoxycholic acid monophosphate) with 5-aminosalicylic acid (5-ASA-UDCA monophosphate) was investigated to determine its suitability for the evaluation of enteric bacteria. This compound, 5-ASA-UDCA monophosphate, was efficiently deconjugated by cholylglycine hydrolase to release 5-ASA, whereas it was completely resistant to deconjugation by pancreatic and intestinal mucosal enzymes. In everted gut sac experiments, 5-ASA-UDCA monophosphate was not actively absorbed from any part of the small intestine. In animal experiments, urinary excretions of N-acetyl-5-ASA (Ac-5ASA) were measured for 24 h following the oral administration of 20 mg of 5-ASA-U DCA monophosphate. Control rats excreted 276.3±89.0 μg (mean±S.E.) of Ac-5ASA, whereas the rats with intestinal bacterial overgrowth excreted more (1224.1 ± 231.5 μg; p0.01). These basic studies indicate that this compound is likely to offer a simple method for the evaluation of microbial overgrowth without the use of radioisotopes or expensive, special apparatus.
Anti-inflammatory effects of 5-aminosalicylic acid conjugates with chenodeoxycholic acid and ursodeoxycholic acid on carrageenan-induced colitis in guinea-pigs
Goto,Okamoto,Yamamoto,Aki
, p. 1711 - 1720 (2001)
Two epimeric bile acid conjugates, 5-aminosalicylic acid-chenodeoxycholic acid (5-ASA-CDCA) and 5-aminosalicylic acid-ursodeoxycholic acid (5-ASA-UDCA), were synthesized to deliver 5-ASA to the large intestine by oral administration. The movement of the conjugates down the gastrointestinal tract and the anti-inflammatory effects on ulcerative colitis were investigated by administering the conjugates to guinea-pigs with an inflammatory bowel disease induced by 2% degraded carrageenan solution. The conjugates were protected from deconjugation in stomach and small intestine and reached the caecum and the colon, where 5-ASA was more easily liberated from 5-ASA-CDCA than from 5-ASA-UDCA. The conjugates at doses equivalent to 50 or 150 mg kg-1 5-ASA were orally administered once a day for 4 weeks from the 15th day after starting carrageenan treatment. The body weights and the bleeding scores of occult blood in faeces were measured during the experiment. The number of ulcers in the caecum and the colon were counted after killing the guinea-pigs at the end of the experiment. Rapid onset of efficacy was shown by a significant reduction in bleeding scores within a week after administration of the conjugates. Treatment with the lower dose of 5-ASA-CDCA showed a recovery of body weight and a significantly decreased number of ulcers in the caecum, and the ulcers in the colon had completely disappeared by the end of the experiment. There was a good correlation found between the number of ulcers in the caecum and the bleeding scores of occult blood in faeces. The findings indicate that both conjugates were sufficiently delivered to the large intestine without deconjugation and that the lower dose of 5-ASA-CDCA is enough for treatment of ulcerative colitis in colonic inflammatory bowel diseases.
Non-amide-based combinatorial libraries derived from N-Boc-iminodiacetic acid: Solution-phase synthesis of piperazinone libraries with activity against LEF-1/β-catenin-mediated transcription
Boger, Dale L.,Goldberg, Joel,Satoh, Shigeki,Ambroise, Yves,Cohen, Steven B.,Vogt, Peter K.
, p. 1825 - 1845 (2007/10/03)
The development of a solution-phase approach to the rapid, parallel synthesis of highly functionalized piperazinones in only four steps starting from N-Boc-iminodiacetic acid is detailed. The efforts represent the extension of the solution-phase synthesis of combinatorial libraries from N-Boc-iminodiacetic acid to non-amide-based libraries where simple liquid-liquid extractions are employed to purify all reaction products. This methodology was applied to the synthesis of a diverse 150-member library with substituents in three positions of the piperazinone core. Screening results from a luciferase reporter assay indicate that a number of library members are novel repressors of LEF-1/β-catenin-mediated transcription, and may be effective agents against colorectal tumors. Two secondary libraries (100 members each) designed from these lead structures were synthesized and screened, providing additional active agents and insight into key structure-activity relationships in the series. These compounds represent only the second class of small molecules which repress transcription of reporter genes containing LEF-1 responsive elements, and the first group not based on DNA minor-groove-binding agents.
