ピリド[2,3-d]ピリミジン系抗菌剤(第5報)1H, 5H-Imidazo[1,2-a]-pyrido[2,3-d]pyrimidine類の合成と反応

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7-Carboxy-9-ethyl-2,3,6,9-tetrahydro-1-methyl-6-oxo-1H-imidazo[1,2-a]pyrido[2,3-d]pyrimidin-4-ium chloride (5), consisting of a new heterocyclic ring system, was produced when 8-ethyl-5,8-dihydro-2-[N-(2-hydroxyethyl)-N-methylamino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acid (3) was treated with SOCl_2. The structure of 5 was assigned on the basis of chemical and spectral evidence. The hydroxide (6) derived from 5 was unstable and was readily converted into a pseudo base (7). Oxidation of 7 with KMnO_4 in alkaline medium gave 5-oxo compound (8). Reduction of 6 or 7 with NaBH_4 afforded 5-unsubstituted 1H, 5H-imidazo[1,2-a]pyrido[2,3-d]pyrimidine derivative (9). The 5-positions of 6 and 7 reacted with methoxide, ethoxide, and carbanions of acetone and nitromethane to give the corresponding 5-methoxy (11), -ethoxy (12), -(2-oxopropyl) (13), and -nitromethyl derivatives (14), respectively. Antibacterial agents, piromidic acid (1) and pipemidic acid (2), as well as 3 were hydrogenated with Pd-C as a catalyst across the 3,4 C=N bond, giving the 3,4-dihydro derivatives 15,16,and 10,respectively. Structure-activity relationships of these compounds were discussed briefly.
公益社団法人日本薬学会の論文
1980-12-25