760170-43-2Relevant academic research and scientific papers
MACROCYCLIC ANTAGONISTS OF THE MOTILIN RECEPTOR FOR TREATMENT OF GASTROINTESTINAL DYSMOTILITY DISORDERS
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Page/Page column 37, (2010/04/30)
The present invention provides conformationally-defined macrocyclic compounds that bind to and/or are functional modulators of the motilin receptor including subtypes, isoforms and/or variants thereof. These macrocyclic compounds, at a minimum, possess adequate pharmacological properties to be useful as therapeutics for a range of disease indications. In particular, these compounds are useful for treatment and prevention of disorders characterized by hypermotilinemia and/or gastrointestinal hypermotility, including, but not limited to, diarrhea, cancer treatment-related diarrhea, cancer-induced diarrhea, chemotherapy-induced diarrhea, radiation enteritis, radiation-induced diarrhea, stress-induced diarrhea, chronic diarrhea, AIDS-related diarrhea, C. difficile associated diarrhea, traveller's diarrhea, diarrhea induced by graph versus host disease, other types of diarrhea, dyspepsia, irritable bowel syndrome, chemotherapy-induced nausea and vomiting (emesis) and post-operative nausea and vomiting and functional gastrointestinal disorders. In addition, the compounds possess utility for the treatment of diseases and disorders characterized by poor stomach or intestinal absorption, such as short bowel syndrome, celiac disease and cachexia. The compounds also have use for the treatment of inflammatory diseases and disorders of the gastrointestinal tract, such as inflammatory bowel disease, ulcerative colitis, Crohn's disease and pancreatitis. Accordingly, methods of treating such disorders and pharmaceutical compositions including compounds of the present invention are also provided.
Potent macrocyclic antagonists to the motilin receptor presenting novel unnatural amino acids
Marsault, Eric,Benakli, Kamel,Beaubien, Sylvie,Saint-Louis, Carl,Deziel, Robert,Fraser, Graeme
, p. 4187 - 4190 (2008/09/19)
Novel, potent small molecule motilin receptor antagonists are described. These peptidomimetic macrocycles are composed of a tripeptide cyclized backbone-to-backbone with a nonpeptidic tether and bear new unnatural amino acids containing basic side chains.
Studies directed toward the design of orally active renin inhibitors. 1. Some factors influencing the absorption of small peptides
Rosenberg,Spina,Woods,Polakowski,Martin,Yao,Stein,Cohen,Barlow,Egan,Tricarico,Baker,Kleinert
, p. 449 - 459 (2007/10/02)
A systematic evaluation of structure-absorption relationships using a high throughput intraduodenal rat screening model has led to the delineation of a set of structural parameters that appear to govern bioavailability in a series of peptide-based renin inhibitors. Optimum structures, exemplified by 25 and 41, incorporated a single, solubilizing substituent at the C- or N- terminus combined with a lipophilic P2-site residue. Both inhibitors gave unprecedented plasma drug levels upon intraduodenal administration to monkeys, and the calculated bioavailability for 41 (14 ± 4%) is the highest reported for any peptidic renin inhibitor.
