著者

細上 徹 榑谷 昌彦 東 邦彦 浅野 昌英 大屋 和美 高杉 紀雄 真船 英一 三木 藤作

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.40, no.10, pp.2712-2719, 1992-10-25 (Released:2008-03-31)

参考文献数

18

被引用文献数

12 14

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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 antiuler activities at oral doses of 50-400 mg/kg.

著者

森田 正美 細上 徹 今野 勉 / 真船 英一 高杉 紀雄 Norio TAKASUGI

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.43, no.3, pp.476-482, 1995-03-15 (Released:2008-03-31)

参考文献数

7

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Preliminary preformulation studies of a 2-(3, 4-dimethoxyphenyl)ethylamine derivative were investigated. The hydrochloride form showed incompatibility with the excipients used for oral dosage forms. There were several crystal forms of the free base, namely, α-anhydrate, β-anhydrate, monohydrate, and trihydrate. The trihydrate form was unstable. The degree of crystallinity of the β-anhydrate form was difficult to control. The monohydrate form was difficult to manufacture with constant quality.The serum levels of the compounds in rats were almost related to the dissolution rates in the JP 1st disintegration medium from the discs. The serum level of α-anhydrate was the lowest. However, the dissolution rates from the formulations of α-anhydrate were improved. After oral administration of the improved formulation, the serum level of α-anhydrate in beagle dogs was almost triple that after the oral administration of the capsule of the hydrochloride form.