124257-72-3Relevant academic research and scientific papers
Synthesis and structure-activity relationships of 4-amino-5-chloro-2- ethoxybenzamides with six- and seven-membered heteroalicycles as potential gastroprokinetic agents
Morie,Kato,Harada,Yoshida,Fujiwara,Matsumoto
, p. 1137 - 1147 (2007/10/02)
A new series of 4-amino-5-chloro-2-ethoxybenzamides 3b-f and 5-8 bearing six- and seven-membered heteroalicycles was prepared and evaluated for gastroprokinetic activity. Compounds 3b-e, derived by replacement of the morpholine oxygen of 4-amino-N-[(4-benzyl-2-morpholinyl)methyl]-5-chloro-2- ethoxybenzamide (3a) with other atoms (sulfur, nitrogen and carbon), generally exhibited a potent gastric emptying activity. N-(4-Benzyl-3- morpholinyl)methylbenzamide (5a) and its analogues 5b-e had weaker activity. However, N-(4-benzyl-3-morpholinyl)ethylbenzamide 8 was as potent as 3a. Benzamides 6a-e, having seven-membered heteroalicycles, showed fairly potent activity. Molecular superimpositions of 5a, 6a and 8 upon 3a using computer graphics suggested that the direction of the N-benzyl group greatly influences the gastric emptying activity, whereas the location of the alicyclic nitrogen is less critical.
Development of potent serotonin-3 (5-HT3) receptor antagonists. I. Structure-activity relationships of 2-alkoxy-4-amino-5-chlorobenzamide derivatives
Harada,Morie,Hirokawa,Yoshida,Kato
, p. 1364 - 1378 (2007/10/02)
A new series of 2-alkoxy-4-amino-5-chlorobenzamide derivatives hearing five- to seven-membered heteroalicyclic rings in the amine moiety was synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activity by assaying the ability to antagonize the yon Bezold-Jarisch reflex in rats. The five- to seven-membered heteroalicycles comprise pyrrolidine, morpholine, 1,4-thiazine, piperidine, piperazine, 1,4-oxazepine, 1,4- thiazepine, azepine, and 1,4-diazepine rings. Among them, some benzamide derivatives having a 1,4-diazepine ring showed a potent 5-HT3 receptor antagonistic activity. In particular, 4-amino-5-chloro-N-(1,4- dimethylhexahydro-1H-1,4-diazepin-6-yl)-2-ethoxyhenzamide (96) and the 1- benzyl-4-methylhexahydro-1H-1,4-diazepine analogue 103 showed potent 5-HT3 receptor antagonistic activity without 5-HT4 receptor binding affinity.
