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.     

Studies on antiulcer drugs. II. Synthesis and antiulcer activities of imidazo[1,2-alpha]pyridinyl-2-alkylaminobenzoxazoles and 5,6,7,8-tetrahydroimidazo[1,2-alpha]pyridinyl derivatives.

A series of imidazo[1,2-alpha]pyridinylbenzoxazoles (4) and 5,6,7,8-tetrahydroimidazo[1,2-alpha]pyridinylbenzoxazoles (5) were synthesized and tested for anti-stress ulcer activity in rats. Several compounds were found to be more active than the reference compounds, sucralfate, cimetidine and ranitidine. Some of them exhibited potent protective activity against ethanol-induced gastric lesion. The synthesis and structure-activity relationships of these compounds are discussed.     

1,3,4-噻二唑基1,2,4-三唑啉酮类化合物的合成及除草活性

以2-甲基-5-氨基-1,3,4-噻二唑和芳香醛为原料,设计合成了一系列新型1,2,4-三唑啉酮类化合物。通过1H MR、MS和元素分析确证了其结构。生物活性测试结果表明,在100μg·m L-1浓度下,该类化合物具有较好的除草活性,其中化合物4c和4d对油菜和稗草的抑制率达到了80%。     

Studies on antiulcer drugs. IV. Synthesis and antiulcer activities of imidazo[1,2-a]pyridinylethylbenzothiazoles and -benzimidazoles.

A series of 6-[2-(imidazo[1,2-a]pyridin-2-yl)ethyl]benzothiazoles (II) and benzimidazole analogues (III) was synthesized and tested for histamine H2-receptor antagonist, gastric antisecretory and anti-stress ulcer activity. A benzimidazole derivative (IIIa) exhibited strong antisecretory activity, whereas the corresponding benzothiazole derivative (IIb) lacked this potency in in vivo test. In contrast to compound IIIa, however, compound IIb demonstrated good inhibition against stress induced ulcer. The structure-activity relationships of these compounds are discussed.     

Studies on antiulcer drugs. I. Synthesis and antiulcer activities of imidazo[1,2-alpha]pyridinyl-2-oxobenzoxazolidines-3-oxo-2H-1,4-benzoxaz ines and related compounds.

A series of imidazo[1,2-alpha]pyridinyl-2-oxobenzoxazolidines (4a-i), -3-oxo-2H-1,4-benzoxazines (5a-q), their thio-analogues (4j-p and 5r-t) and 5,6,7,8-tetrahydroimidazo[1,2-alpha]pyridinyl derivatives (8 and 9) were synthesized and tested for anti-stress ulcer activity in rats. Several compounds were found to be more active than the reference compounds, zolimidine, cimetidine and sucralfate. Among them, compound 4e, 5i and 5l also exhibited potent protective activity against ethanol-induced gastric lesion. The synthesis and structure-activity relationships of these compounds are discussed.     

Molecular conformations of aminophenylimidazoles exhibiting antiulcer activities

To experimentally clarify a possible stereostructure-activity relationship proposed for H2-receptor antagonists, three 5-aminophenylimidazoles (1, 2 and 3), in which respective amino groups are located on the ortho, meta and para positions of the benzene ring, were synthesized and examined for their conformational characteristics using X-ray diffraction and proton nuclear magnetic resonance (1H-NMR) methods, and for antiulcer activities on rats and H2-receptor antagonist activities in guinea pig. The ortho isomer 1, which preferentially formed an intramolecular N-H (amino)...N (imidazole) hydrogen bond, showed the highest antiulcer activity with half the efficacy of cimetidine. On the other hand, none of 1, 2 and 3 showed significant H2-receptor antagonist activity. Based on these results, the conformational characteristic for the exhibition of antiulcer activity has been discussed.     

Studies on antiulcer drugs. III. Synthesis and antiulcer activities of imidazo[1,2-a]pyridinylethylbenzoxazoles and related compounds. A novel class of histamine H2-receptor antagonists.

A series of imidazo[1,2-a]pyridinylalkylbenzoxazole derivatives was synthesized and tested for histamine H2-receptor antagonist, gastric antisecretory and antiulcer activities. Some of 2-amino-6-[2-(imidazo[1,2-a]pyridin-2-yl)ethyl]benzoxazole derivatives were found to have good pharmacological activities. Among them, 2-amino-6-[2-(7-methoxy-3-methylimidazo[1,2-a]pyridin-2-yl)ethyl] benzoxazole (II-11) and 2-acetamido-6-[2-(7-methylimidazo[1,2-a]pyridin-2-yl)ethyl] benzoxazole (II-38) showed potent antisecretory and cytoprotective activity. The structure-activity relationships of these compounds are discussed.