159026-17-2Relevant articles and documents
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.
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.
