1 0 0 0 スルホキシドとアシル化剤の反応
- 著者
- 藤井 達也 西田 裕 阿比留 佳明 山本 雅司 黄瀬 正博
- 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.11, pp.1872-1877, 1995-11-15 (Released:2008-03-31)
- 参考文献数
- 13
- 被引用文献数
- 7 19
Diisopropylamine (DIPA), N, N-diisopropylethylamine (DIPEA), tributylamine (TNBA) and 7-(1-piperazinyl)-4-quinolone-3-carboxylic acid (2) were titrated in water-dimethylformamide (DMF) mixtures containing 45-98% DMF. Apparent pKa values in anhydrous DMF (pKDMF) were calculated by extrapolation from the variation in the half-neutralization pH values in aqueous DMF. The validity of the relative basicity derived from the pKDMFs was confirmed by examination of the kinetics of esterification of a derivative of 2 with 4-(bromomethyl)-5-methyl-1, 3-dioxol-2-one (DMDO-Br). Relative basicities in DMF were : the carboxylate anion of 2»DIPA>DIPEA>TNBA >the amino group in the piperazinyl part of 2. This order is clearly different from that observed in water.We concluded that DIPEA is a suitable agent to suppress the undesired esterification during the reaction to mask the amino group of 2 with a DMDO group, because it does not remove a proton from the carboxyl group, but only from the protonated amino group.
- 著者
- 瀬川 純 数野 憲二 松岡 正人 網本 功 尾崎 正邦 松田 真人 冨井 由文 北野 正彦 黄瀬 正博
- 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.7, pp.1238-1240, 1995-07-15 (Released:2008-03-31)
- 参考文献数
- 13
- 被引用文献数
- 3 7
Optically active isomers of 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1, 3]thiazeto[3, 2-a]quinoline-3-carboxylic acid (NM394, 3) were prepared through optical resolution of their racemic intermediate (±)-1 by high-performance liquid chromatography (HPLC). The absolute configuration at the C-1 position in the thiazetoquinolone ring of (-)-3 was confirmed by X-ray analysis of (-)-4 to be S. The in vitro antibacterial activity of (-)-3 was 2-8 times that of (+)-3.
- 著者
- 瀬川 純 数野 憲二 松岡 正人 白波瀬 一朗 尾崎 正邦 松田 真人 冨井 由文 北野 正彦 黄瀬 正博
- 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.1, pp.63-70, 1995-01-15 (Released:2008-03-31)
- 参考文献数
- 19
- 被引用文献数
- 6 13
A seried of 1, 8-disubstituted 6-fluoro-4-oxo-7-piperazinyl-4H-[1, 3]thiazeto[3, 2-a]quinoline-3-carboxylic acid derivatives was prepared and evaluated for antibacterial activity. In the 7-piperazinyl series, addition of a fluorine at C-8, which increased the in vitro activity for the 1-hydrogen and 1-methyl analogues and decreased it for the 1-phenyl analogue, improved the in vivo activity of all the analogues. Introduction of a methoxy group at C-8 of the 1-methyl-7-piperazinyl analogue also improved its in vivo antibacterial activity. The effect of 8-substituents on the in vitro and in vivo antibacterial activity of the 1-methyl-7-(4-methyl-1-piperazinyl) series is also discussed.
- 著者
- 森田 岩男 国本 克俊 津田 正己 但田 信一 黄瀬 正博 木村 喜代史
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- Chemical & pharmaceutical bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.35, no.10, pp.4144-4154, 1987-10-25
A series of 1,4-dihydropyridine-5-cyclic phosphonate derivatives, designed as analogues of 1,4-dihydropyridine-3,5-dicarboxylate calcium antagonists, was synthesized and examined for antihypertensive activity. Several compounds were proved to have activities superior or comparable to that of nifedipine in lowering blood pressure in normotensive and spontaneously hypertensive rats (SHR). Among these compounds, methyl 2,6-dimethyl-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4(2-nitrophenyl)-1,4-dihydropyridine-3-carboxylate (31, DHP-218) was approximately 7 times more active than nifedipine in SHR and was selected for further development and clinical evaluation. The structure-activity relationships are discussed.
- 著者
- 森田 岩男 津田 正己 黄瀬 正博 杉山 信
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- Chemical & pharmaceutical bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.36, no.3, pp.1139-1142, 1988-03-25
Attempts were made to improve the synthesis of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate (DHP-218), a new calcium antagonist. 2-Acetonyl-2-oxo-1,3,2-dioxaphosphosphorinane (5a), the key intermediate, was prepared from the allenylphosphonate (2) via the enaminophosphonate (4) in a good yield. Subsequently, the Knoevenagel condensation using 5a and the imine (6a) gave the benzylideneacetonylphosphonate (7a) in a good yield without the use of the Horner-Emons reaction. This condensation also gave good results for other acetonylphopshonates. The final step gave DHP-218 in a good yield through a modified Hantzsch synthesis with the use of a dehydrating agent. The overall yield was increased from 1.7% to 22%.
- 著者
- 瀬川 純 数野 憲二 松岡 正人 白波瀬 一朗 尾崎 正邦 松田 真人 冨井 由文 北野 正彦 黄瀬 正博
- 出版者
- 公益社団法人日本薬学会
- 雑誌
- Chemical & pharmaceutical bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.43, no.1, pp.63-70, 1995-01-15
A seried of 1,8-disubstituted 6-fluoro-4-oxo-7-piperazinyl-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid derivatives was prepared and evaluated for antibacterial activity. In the 7-piperazinyl series, addition of a fluorine at C-8,which increased the in vitro activity for the 1-hydrogen and 1-methyl analogues and decreased it for the 1-phenyl analogue, improved the in vivo activity of all the analogues. Introduction of a methoxy group at C-8 of the 1-methyl-7-piperazinyl analogue also improved its in vivo antibacterial activity. The effect of 8-substituents on the in vitro and in vivo antibacterial activity of the 1-methyl-7-(4-methyl-1-piperazinyl) series is also discussed.