24260-31-9Relevant articles and documents
Studies on novel 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones as potential TACE inhibitors: Design, synthesis, molecular modeling, and preliminary biological evaluation
DasGupta, Shirshendu,Murumkar, Prashant R.,Giridhar, Rajani,Yadav, Mange Ram
experimental part, p. 3604 - 3617 (2009/09/30)
Compounds belonging to the class of 2-imidazolidinones and tetrahydropyrimidin-2(1H)-ones were synthesized and evaluated for their TACE inhibitory activity. Most of the compounds showed very good TACE inhibitory activity. Docking study clearly indicates importance of the P1′ group of the inhibitor for the TACE inhibitory activity. This work proves that these two classes of molecules could be used as potential leads for the development of TACE inhibitors.
5-HT3 Receptor Antagonists. 3. Quinoline Derivatives Which May Be Effective in the Therapy of Irritable Bowel Syndrome
Kishibayashi, Nobuyuki,Miwa, Yoshikazu,Hayashi, Hiroaki,Ishii, Akio,Ichikawa, Shunji,et al.
, p. 3286 - 3292 (2007/10/02)
A series of quinolinecarboxylic acid derivatives has been previously described as a new class of 5-HT3 receptor antagonists due to deviation of a carbonyl moiety from the plane of an aromatic ring in their minimum-energy conformations.These derivatives were evaluated in a wrap-restraint stress-induced defecation model in rats.Reference compounds, ondansetron (1), granisetron (2), and YM060 (4), potently inhibited a stress-induced increase in stools excreted from fed rats (ID50 = 0.27, 0.12, and 0.0052 mg/kg, po, respectively).However, quinoline derivatives exhibited different activities depending on structural class. 4-Hydroxyquinoline-3-carboxylic acid derivatives 5 and 6a possess high affinity for the 5-HT3 receptor (Ki = 6.1 and 1.5 nM, respectively) and exhibit potent activity in the Bezold-Jarisch (B-J) reflex test (ED50 = 0.0017 and 0.00010 mg/kg, iv, respectively), but they did not effectively inhibit the increase in fecal pellet output at the dose of 1 mg/kg, po.On the other hand, most of 1-substituted 2-oxoquinoline-4-carboxylates 10 showed less potent activity in the B-J reflex test than 1 or 2 but inhibited restraint stress-induced defecation more potently than 1 or 2.The ID50 value of endo-8-methyl-8-azabicyclooct-3-yl 1-isobutyl-2-oxo-1,2-dihydro-4-quinolinecarboxylate 10e was 0.013 mg/kg, po.With respect to the selected compounds 6a and 10e, effects on 5-HT- and thyrotropin-releasing hormone (TRH)-induced defecation, castor oil-induced diarrhea and wrap-restraint stress-induced colonic propulsion in rats were examined.These 5-HT3 receptor antagonists did not effectively inhibit castor oil-induced diarrhea, which has been reported not to be mediated via the 5-HT3 receptor.Although 10e showed 800-fold decreased potency compared with 4 in the B-J refles test, 10e exhibited activity as potent as 4 in 5-HT- and TRH-induced defecation assays; 10e exhibited 7-fold increased potency compared with 4 in wrap-restraint stress-induced colonic propulsions.From these results, 10e appears to interact selectively with 5-HT3 receptors in the gastrointestinal system and might be effective in the therapy of irritable bowel syndrome (IBS).
