- NOVEL PYRIDONE CARBOXYLIC ACID DERIVATIVE OR SALT THEREOF
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It is intended to provide a novel compound having high antitumor activity and low toxicity to normal cells. The present invention provides a pyridone carboxylic acid derivative represented by the following formula (1) or a salt thereof wherein R1 represents a hydrogen atom, a halogen atom or the like; R2 represents a hydrogen atom, a halogen atom or the like; R3 to R6 each represent a hydrogen atom or the like; R7 represents a hydrogen atom or the like; R8 represents a hydrogen atom, a halogen atom, the following formula (a) (wherein Ra1 and Ra2 each represent a hydrogen atom, a hydroxy group, an optionally substituted lower alkyl group or the like) or the like, or R7 and R8 together represent —N—OR10 (wherein R10 represents a hydrogen atom, an optionally substituted lower alkyl group, or an aralkyl group), or R7 and R8 form an optionally substituted 4- to 6-membered saturated hetero ring together with the adjacent carbon atom, or the like; R9 represents a hydrogen atom or the like; X represents a nitrogen atom or the like; and Y represents a nitrogen atom or the like.
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Paragraph 0454-0456; 0474-0476
(2020/03/09)
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- Synthesis and in vitro antitumor activity of novel naphthyridinone derivatives
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A series of naphthyridinone derivatives based on 1a (a precursor of Voreloxin) were designed and synthesized. Seven compounds having >70% inhibition against HL60 at 30 μmol/L were further evaluated for their in vitro antitumor activity by SRB assay. Results reveal that thiazol-2-yl and 3-aminomethyl-4-benzyloxyimino-3-methylpyrrolidin-1-yl groups are optimal at the N-1 and C-7 positions of naphthyridinone core, respectively. 10j exhibits broad-spectrum activity (IC50: 100-fold more potent than the two references against eight of these cell lines.
- Jia, Xue-Dong,Wang, Shuo,Wang, Ming-Hua,Liu, Ming-Liang,Xia, Gui-Min,Liu, Xiu-Jun,Chai, Yun,He, Hong-Wei
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p. 235 - 239
(2017/01/28)
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- STABLE SNS-595 COMPOSITIONS AND METHODS OF PREPARATION
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Methods of preparing substantially pure SNS-595 substance are disclosed. Also provided are compositions comprising SNS-595 substance that are substantially pure and essentially free of visible particles.
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Page/Page column 53; 54
(2011/04/14)
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- METHOD OF PREPARING (+)-1,4-DIHYDRO-7-[(3S,4S)-3METHOXY-4-(METHYLAMINO)-1-PYRROLIDINYL]-4-OXO-1-(2-THIAZOLYL)-1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID
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Methods of preparing (+)-1, 4-dihydro-7-[(3S,45)-3-methoxy-4-(methylamino)-1 - pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid are disclosed. Also provided are pharmaceutical compositions comprising (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid, and methods of treatment using such compositions.
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Page/Page column 3
(2010/08/04)
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- Synthesis and Structure-Activity Relationships of Novel 7-Substituted 1,4-Dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acids as Antitumor Agents. Part 2
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We have previously reported that a series of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids possess moderate cytotoxic activity. In a further attempt to find clinically useful antitumor agents, we investigated the structure-activity relationships (SARs) of a new series of compounds obtained by changing the C-6 position of the fluorine atom in addition to the C-5 and C-7 positions and evaluating their cytotoxic activity against several murine and human tumor cell lines. Our results showed that the 6-unsubstituted 1,8-naphthyridine structure had the most potent cytotoxic activity against murine P388 leukemia twice that of the 6-fluoro analogue. In addition, introduction of an amino group at the C-5 position did not have any substantial effect on the cytotoxic activity, while both the 5-chloro and 5-trifluoromethyl groups decreased the cytotoxic activity by 5- to 10-fold. Moreover, aminopyrrolidine derivatives at the C-7 position showed more potent cytotoxic activity than other amines or carbon derivatives. Among the 7-(3-aminopyrrolidinyl) derivatives, the trans-3-methoxy-4-methylaminopyrrolidinyl derivative (271) was determined to have potent cytotoxic activity in both in vitro and in vivo assays and high water solubility. Finally, the (S,S)-isomer (AG-7352, 3) of 271, with a cytotoxic activity against human tumor cell lines more potent than that of etoposide, was selected for further development.
- Tsuzuki, Yasunori,Tomita, Kyoji,Shibamori, Koh-Ichiro,Sato, Yuji,Kashimoto, Shigeki,Chiba, Katsumi
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p. 2097 - 2109
(2007/10/03)
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- Compounds, processes for the preparation thereof and anti-tumor agents
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This invention relates to pyridone-carboxylic acid derivatives of the following formula or salts thereof: STR1 wherein R1 is a hydrogen atom, a halogen atom, etc., R2 is a carboxyl group etc., R3 is a hydrogen atom etc., A
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