92299-77-9Relevant articles and documents
A new series of 6-chloro-2,3-dihydro-4(1H)-quinazolinone derivatives as antiemetic and gastointestinal motility enhancing agents
Baldazzi, Claudia,Barbanti, Miriam,Basaglia, Roberta,Benelli, Augusta,Bertolini, Alfio,Piani, Silvano
, p. 911 - 918 (2007/10/03)
New 6-chloro-2,3-dihydro-4(1H)-quinazolinones (24-27) have been synthesized and evaluated for gastrointestinal prokinetic and antiemetic activities in comparison with structurally related benzamides (21-22) and 6-chloro-2,3-dihydro-(1H)-1,3-benzoxazolin-4-ones (28). Their key pharmacophoric element has been defined as a 6-membered ring replacing the 'virtual ring' arising from the hydrogen bond between amidic nitrogen and methoxy group in metoclopramide (1) and structurally related benzamides (2-10). Variations of heterocycle ing groups have pointed out that a lipophilic aromatic group in position 1 plays an important role for pharmacological properties, while the steric restriction and the modification of the side-chain nucleophilicity are uneffective both for the in vitro and in vivo activity. Some of these compounds very effectively enhance gut peristaltic activity in vitro (rabbit jejunum), increase gastric emptying of a semisolid meal (in rats), and inhibit cisplatin-induced emesis (in pigeons), favourably comparing with cisapride.
