- 著者
- 三塩 晋作 廣瀬 徹 中野 純次 松本 純一
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.107, no.8, pp.634-639, 1987-08-25 (Released:2008-05-30)
- 参考文献数
- 6
A mode of the alkaline and acidic degradation of sodium 6-[D-2-(2-(4-formyl-1-piperazinyl)-5, 8-dihydro-5-oxopyrido [2, 3-d] pyrimidine-6-carboxamido)-p-hydroxyphenylacetamido] penicillanate (1, PL-385) and structures of the degradation products were studied. Treatment of 1 with three equimolar amounts of sodium hydroxide produced a kinetically stable intermediate, (5R)-penicilloic acid (2a), which on kept at 37°C for 65h was converted into a thermodynamically stable product, (5S)-penicilloic acid (2b). Treatment of 1 with an excess of sodium hydroxide gave a deformyl derivative (3) arising from the elimination of formly group via 2. On the acidic treatment of 1, the degradation product, (5R, S)-penilloic acid (4), was yielded.
- 著者
- 三塩 晋作 廣瀬 徹 中野 純次 松本 純一
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.107, no.8, pp.607-615, 1987-08-25 (Released:2008-05-30)
- 参考文献数
- 11
- 被引用文献数
- 1 1
A series of N-alkylampicillin (2), N-heteroarylampicillin (5) and N-heteroarylcephalexin (6) were synthesized in order to obtain β-lactam detivatives with a broad and orallypotent antibacterial activity similar to that of the injectable N-acylampicillins. 6-[2-[(Pyrido [2, 3-d] pyrimidin-6-yl) methylamino]-2-phenylacetamido] penicillanic acid derivatives (2) were prepared by the reduction of the Schiff base which was derived from the reaction of pyrido [2, 3-d] pyrimidine-6-carboxaldehyde (1) with ampicillin. 6-N-(4-Pyrimidinyl) ampicillin and -cephalexin derivatives (5 and 6) were obtained by the reaction of 4-chloropyrimidine (4) with ampicillin or cephalexin. Compounds 2, 5 and 6 were tested in vitro antibacterial activity and, however, none of them have a broad and potent activity.
- 著者
- 三塩 晋作 廣瀬 徹 中野 純次 松本 純一 南 新作
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- YAKUGAKU ZASSHI (ISSN:00316903)
- 巻号頁・発行日
- vol.107, no.8, pp.592-606, 1987-08-25 (Released:2008-05-30)
- 参考文献数
- 11
- 被引用文献数
- 1 1
A series of N-(pyrido [2, 3-d] pyrimidine-6-carbonyl) ampicillin and -amoxicillin derivatives (1-3) were synthesized and tested for antibacterial activity and acute toxicity in mice. 5, 8-Dihydro-2-(1-piperazinyl)-5-oxopyrido [2, 3-d] pyrimidine-6-carboxylic acid (7) was converted to N-acyl- and -alkylpiperazinyl derivatives (8 and 9) by acylation and alkylation, respectively ; a part of 9 was alternatively prepared by the reactions involving the displacement of N-alkylpiperazines with sulfoxide 11 which was derived from ethyl 5, 8-dihydro-2-methylthio-5-oxopyrido [2, 3-d] pyrimidine-6-carboxylate (10). Treatment of 4, 5, 8 and 9 with ethyl chloroformate followed by the reaction with ampicillin and amoxicillin gave the desired N-acylampicillin (2) and -amoxicillins (1 and 3), respectively. Among compounds 1-3, sodium 6-[D-(-)-2-(2-(4-formyl-1-piperazinyl)-5, 8-dihydro-5-oxopyrido [2, 3-d] pyrimidine-6-carboxamido)-p-hydroxyphenylacetamido] penicillanate (3l, PL-385) was found to be the most excellent in antibacterial activity and to be the less potent in acute toxicity in mice. An alternative route for the synthesis of PL-385 was accomplished, consisting of the reaction of an active ester 13 with amoxicillin. Structure-activity relationships of 1-3 were discussed.