Studies on pyridonecarboxylic acids . 2. Synthesis and antibacterial activity of 8‐substituted‐7‐fluoro‐5‐oxo‐5H‐thiazolo[3,2‐a]quinoline‐4‐carboxylic acids

Segawa, Jun; Kitano, Masahiko; Kazuno, Kenji; Tsuda, Masami; Shirahase, Ichiro; Ozaki, Masakuni; Matsuda, Masato; Kise, Masahiro

doi:10.1002/jhet.5570290514

Cited by 17 publications

(18 citation statements)

References 14 publications

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“…NM394 is the first thiazetoquinoline carboxylic acid derivative reported to have potent antibacterial activity [4,5], but we have found it to be poorly absorbed when orally administered. As we thought that the low bioavailability of NM394 was due to its high hydrophilicity (log p = -0.86), we have synthesized 37 derivatives which includes lipophilic prodrug moieties in order to improve the absorption of NM394 from the intestinal tract.…”

Section: Discussionmentioning

confidence: 99%

“…However, we have studied quinolone derivatives with a bridge connecting the N-1 and C-2 positions in the expectation that the resulting tricyclic structure would retain antibacterial activity. We have found that such thiazolo-and thiazetoquinoline carboxylic acid derivatives have potent in vitro antibacterial activity [4,5]. Among the derivatives tested, 1 (NM394), 6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H- [1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid ( fig.…”

Section: Introductionmentioning

confidence: 99%

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In vivo Antibacterial Activity of a Prodrug of NM394, a Thiazetoquinoline Carboxylic Acid Derivative

et al. 1997

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NM394 (6-fluoro-1-methyl-4-oxo-7-(1-piperazinyl)-4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylic acid) has potent, broad-spectrum antibacterial activity in vitro, but not in vivo. To increase the bioavailability of NM394, various prodrugs were synthesized and tested. One of them, NM441, an N-(5-methyl-2-oxo-1,3-dioxol-4-yl) derivative, showed potent in vivo antibacterial activity. Using thin-layer chromatography-bioautography, we confirmed that after oral administration, NM441 was readily absorbed and hydrolyzed to NM394. Other prodrugs of NM394 were only partially metabolized to NM394. In pharmacokinetic studies in mice and monkeys, we found that the blood levels of NM394 were 7.8 and 5.9 times greater, respectively, when NM441 rather than NM394 was administered. These findings suggest that NM441 is an effective prodrug of NM394.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vivo Antibacterial Activity of a Prodrug of NM394, a Thiazetoquinoline Carboxylic Acid Derivative

et al. 1997

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“…Their action is associated with inhibiting DNA gyrase and preventing duplication of bacterial DNA [ 2 ]. The presence of a sulfur atom in the 2 position of the quinoline moiety increases antibacterial activity [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Therefore, 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylates are interesting for the development of new effective bactericide compounds.…”

Section: Introductionmentioning

confidence: 99%

Methylation of Methyl 4-Hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate: Synthetic, Crystallographic, and Molecular Docking Studies

et al. 2020

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Consecutive alkylation of 4-hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate by CH3I has been investigated to establish regioselectivity of the reaction for reliable design and synthesis of combinatorial libraries. In the first stage, the product of S-methylation-methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate was obtained. The subsequent alkylation with CH3I led to the formation of both O- and N-methylation products mixture-methyl 4-methoxy-2-(methylthio)quinoline-3-carboxylate and methyl 1-methyl-2-(methylthio)-4-oxo-1,4-dihydroquinoline-3-carboxylate with a predominance of O-methylated product. The structure of synthesized compounds was confirmed by means of elemental analysis, 1H-NMR, 13C-NMR, LC/MS, and single-crystal X-ray diffraction. The quantum chemical calculations of geometry and electron structure of methyl 4-hydroxy-2-(methylthio)quinoline-3-carboxylate’s anion were carried out. According to molecular docking simulations, the studied compounds can be considered as potent inhibitors of Hepatitis B Virus replication. Experimental in vitro biological studies confirmed that studied compounds demonstrated high inhibition of HBV replication in 10 µM concentration.

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“…The structure of this novel molecule was elucidated by 1 H-NMR, 13 C-NMR, HR-MS, and X-ray crystallography. Despite the availability of several literatures on the syntheses and bioactivity of angular 4-oxo-thiazolo[3,2-a]quinoline-3-carboxylic acid derivatives, [4][5][6][7][8][9] there are limited reports on the synthesis of 4-oxo-thiazeto[3,2-a]quinolines [10][11][12][13][14][15][16] and there is no reported synthesis of 4-oxo-benzo[h]thiazeto [3,2-a]quinoline derivatives.…”

Section: Introductionmentioning

confidence: 99%

Polycyclic Quinolones (Part 2) — Synthesis of Novel 4-Oxo-1,4-dihydrobenzo[h]-[1,3]thiazeto[3,2-a]quinoline Carboxylic Acids via Oxidative Cyclization of the Corresponding 2-Mercaptoquinoline Precursors

Ahmed¹,

Daneshtalab²

2012

HETEROCYCLES

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The first synthesis of a series of 4-oxo-1,4-dihydrobenzo[h][1,3]thiazeto[3,2-a]quinoline carboxylic acids and their esters via oxidative cyclization of ethyl 2-((2-ethoxy-2-oxoethyl)thio)-4-hydroxybenzo-[h]quinoline-3-carboxylate derivatives in the presence of a vicinal dihaloalkane, KI, and K 2 CO 3 is described. Structures of the synthesized compounds were characterized by spectrometric and X-ray crystallographic analyses.

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Studies on pyridonecarboxylic acids . 2. Synthesis and antibacterial activity of 8‐substituted‐7‐fluoro‐5‐oxo‐5H‐thiazolo[3,2‐a]quinoline‐4‐carboxylic acids

Cited by 17 publications

References 14 publications

In vivo Antibacterial Activity of a Prodrug of NM394, a Thiazetoquinoline Carboxylic Acid Derivative

In vivo Antibacterial Activity of a Prodrug of NM394, a Thiazetoquinoline Carboxylic Acid Derivative

Methylation of Methyl 4-Hydroxy-2-thioxo-1,2-dihydroquinoline-3-carboxylate: Synthetic, Crystallographic, and Molecular Docking Studies

Polycyclic Quinolones (Part 2) — Synthesis of Novel 4-Oxo-1,4-dihydrobenzo[h]-[1,3]thiazeto[3,2-a]quinoline Carboxylic Acids via Oxidative Cyclization of the Corresponding 2-Mercaptoquinoline Precursors

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