Abstract
A series of 8-substituted-9,1-(epoxymethano)-7-fluoro-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids having a novel tetracyclic structure was synthesized and tested for antibacterial activity. The nature of the heteroatom (N, O, or S) substituted at the 8-position had little influence on the antibacterial activity. Among the six pyrrolidinyl derivatives and the five piperazinyl derivatives, the 8-(3-hydroxy-1-pyrrolidinyl) derivative 6h and the hydrochloride of the 8-(4-methyl-1-piperazinyl) derivative 61 showed the most potent activity against both Gram-positive and Gram-negative bacteria. Against nalidixic acid resistant strains, isolated from Escherichia coli KC-14, compound 6h was less potent than 6I. Replacement of the piperazinyl nitrogen atom by a carbon atom, an oxygen atom, or a sulfur atom (corresponding to the piperidine, morpholine, or thiomorpholino group, respectively) enhanced the activity against Gram-positive bacteria, but reduced the activity against Gram-negative bacteria. Compound 61 also showed potent in vivo antibacterial activity against Gram-positive and Gram-negative bacteria, and did not cause convulsions in mice with the concomitant administration of fenbufen. Replacement of the car boxy group by a sulfonic acid group in 6I resulted in a complete loss of antibacterial activity.
| Original language | English |
|---|---|
| Pages (from-to) | 94-99 |
| Number of pages | 6 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 35 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 1 1992 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery
Cite this
Synthesis and Antibacterial Activity of New Tetracyclic Quinolone Antibacterials. / Taguchi, Masahiro; Hondo, Hirosato; Inoue, Yoshimasa; Kawahata, Yoshihiro; Jinbo, Yoshikazu; Sakamoto, Fumio; Tsukamoto, Goro.
In: Journal of Medicinal Chemistry, Vol. 35, No. 1, 01.01.1992, p. 94-99.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Synthesis and Antibacterial Activity of New Tetracyclic Quinolone Antibacterials
AU - Taguchi, Masahiro
AU - Hondo, Hirosato
AU - Inoue, Yoshimasa
AU - Kawahata, Yoshihiro
AU - Jinbo, Yoshikazu
AU - Sakamoto, Fumio
AU - Tsukamoto, Goro
PY - 1992/1/1
Y1 - 1992/1/1
N2 - A series of 8-substituted-9,1-(epoxymethano)-7-fluoro-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids having a novel tetracyclic structure was synthesized and tested for antibacterial activity. The nature of the heteroatom (N, O, or S) substituted at the 8-position had little influence on the antibacterial activity. Among the six pyrrolidinyl derivatives and the five piperazinyl derivatives, the 8-(3-hydroxy-1-pyrrolidinyl) derivative 6h and the hydrochloride of the 8-(4-methyl-1-piperazinyl) derivative 61 showed the most potent activity against both Gram-positive and Gram-negative bacteria. Against nalidixic acid resistant strains, isolated from Escherichia coli KC-14, compound 6h was less potent than 6I. Replacement of the piperazinyl nitrogen atom by a carbon atom, an oxygen atom, or a sulfur atom (corresponding to the piperidine, morpholine, or thiomorpholino group, respectively) enhanced the activity against Gram-positive bacteria, but reduced the activity against Gram-negative bacteria. Compound 61 also showed potent in vivo antibacterial activity against Gram-positive and Gram-negative bacteria, and did not cause convulsions in mice with the concomitant administration of fenbufen. Replacement of the car boxy group by a sulfonic acid group in 6I resulted in a complete loss of antibacterial activity.
AB - A series of 8-substituted-9,1-(epoxymethano)-7-fluoro-5-oxo-5H-thiazolo[3,2-a]quinoline-4-carboxylic acids having a novel tetracyclic structure was synthesized and tested for antibacterial activity. The nature of the heteroatom (N, O, or S) substituted at the 8-position had little influence on the antibacterial activity. Among the six pyrrolidinyl derivatives and the five piperazinyl derivatives, the 8-(3-hydroxy-1-pyrrolidinyl) derivative 6h and the hydrochloride of the 8-(4-methyl-1-piperazinyl) derivative 61 showed the most potent activity against both Gram-positive and Gram-negative bacteria. Against nalidixic acid resistant strains, isolated from Escherichia coli KC-14, compound 6h was less potent than 6I. Replacement of the piperazinyl nitrogen atom by a carbon atom, an oxygen atom, or a sulfur atom (corresponding to the piperidine, morpholine, or thiomorpholino group, respectively) enhanced the activity against Gram-positive bacteria, but reduced the activity against Gram-negative bacteria. Compound 61 also showed potent in vivo antibacterial activity against Gram-positive and Gram-negative bacteria, and did not cause convulsions in mice with the concomitant administration of fenbufen. Replacement of the car boxy group by a sulfonic acid group in 6I resulted in a complete loss of antibacterial activity.
UR - http://www.scopus.com/inward/record.url?scp=0026529070&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026529070&partnerID=8YFLogxK
U2 - 10.1021/jm00079a011
DO - 10.1021/jm00079a011
M3 - Article
C2 - 1310116
AN - SCOPUS:0026529070
VL - 35
SP - 94
EP - 99
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 1
ER -