Syntheses of 2-(3,4-dimethoxyphenyl)ethylamine derivatives and their antiulcer activities.
A series of acyl derivatives of 2-(3,4-dimethoxyphenyl)ethylamine (4) were synthesized and evaluated for their effectiveness to prevent water-immersion stress-induced gastric ulceration when given intraperitoneally to rats. Among them N-[2-(3,4-dimethoxyphenyl)ethyl]-2-phenylaminoacetamide hydrochloride (15) had significant antiulcer activity. Further modification of the four parts of 15 revealed that only the introduction of a carbamoyl group into 2- or 3-position of the phenylamino part gave compounds (49-51, 54 and 55) which retained antiulcer activity comparable to the lead compound. However, the compounds (49-51 and 54) did not exert a prophylactic effect when administered orally except for the 3-substituted bezamide derivative 55. Alkyl substitution on the nitrogen of benzamide gave 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl] amino-N-methylbenzamide (66, DQ-2511) and the related compounds (67, 70, 74 and 77) which all had potent antiulcer activities at oral doses of 50-400 mg/kg.
Hosokami
T
T
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Kuretani
M
M
Higashi
K
K
Asano
M
M
Ohya
K
K
Takasugi
N
N
Mafune
E
E
Miki
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D005021:Ethylamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000897:Anti-Ulcer Agents; D005021:Ethylamines