• Archives of Pharmacal Research
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• 제29권5호
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• pp.369-374
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• 2006

An efficient method for the synthesis of optically active 2-substituted 2,3-dihydro-4-quinolones has been developed. The key features include the introduction of a chiral side chain and the construction of quinolone skeleton by Mitsunobu alkylation and hydroarylation, respectively.

• 대한화학회지
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• 제41권4호
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• pp.214-218
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• 1997

• Bulletin of the Korean Chemical Society
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• 제25권8호
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• pp.1269-1272
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• 2004

• 약학회지
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• 제52권6호
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• pp.514-519
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• 2008

We developed a convenient synthetic route to 3-alkylated 2-phenyl-4-quinolone derivatives (4a-h and 5a-c), which were expected to retain antitumor activity. A series of 2,3-dihydro-2-hydroxy-2-phenyl-4-quinolones (3a-h) was synthesized through dehydration, dealcoholation and hydration using acid-catalyzed one-pot reaction from anilines and ethyl benzoylacetates. 3-Methyl (or 3,3-dimethyl)-2-phenyl-4-quinolone derivatives 4 and 5 were synthesized from 3a-h through the methylation using methyl iodide. Formation of quinolone nucleus was undertaken with p-toluenesulfonic acid (p-TSA) at $90{\sim}110^{\circ}C$ in toluene for 3${\sim}$7.5 hr over the Dean-Stark apparatus. The key intermediates in these preparations are ${\beta}$-ketoesters 2a-h, which can be readily obtained from the corresponding anilines 1a-e by reaction with ethyl bezoylacetates.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1993년도 제2회 신약개발 연구발표회 초록집
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• pp.118-118
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• 1993

퀴놀론 모핵의 합성은 기존에 알려진 합성 방법인 Could-Jacobs방법과 Bayer방법에 의해서 Intermediate로 사용된 7-chloro-1-ethyl-6-fluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid와 1-cyclopropyl-7-chloro-6-Fluoro-1,4-dihydro-4-oxoquinolne-3-carboxylic acid를 합성하였다. Heteroaromatic tin compound는 furan, thiophene, 3-bromopyridine, 2-fluoropyridine에 n-BuLi을 사용하여 metallation 한후 electrophile로 tributyltin chloride를 사용하여 2-tributylstannofuran, 2-tributylst-annothiophene, 3-tributylstannopyridine, 2- fluoro-2-tributylstannop-yridine을 합성할 수 있었다. 이상의 Intermediate와 tin compounds를 p-alladium 촉매하에서 반응시켜 1-ethyl-7-(2-furanyl)-6-fluoro-1,4-dihy-dro-4-oxo-3-quinoline-carboxylic acid (compound 3), 1-ethyl-7-(2-th-iophenyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinol in carboxylic acid(compound 5), 1-ethyl-7-(3-pyridinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 7), 1-ethyl-7-(2-fluoro-3-pyrid-nyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 9), 1-cyclopropyl-7-(2-furanyl) -6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 4), 1-cyclopropyl-7-(2-thiophenyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 6) ,1-cyclopropyl-7-(3-pyridinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 8), 1-cyclopropyl-7-(2-fluoro-3-pyridinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acid (compound 10)를 합성하였다.

• Bulletin of the Korean Chemical Society
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• 제27권8호
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• pp.1249-1252
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• 2006

• 약학회지
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• 제40권6호
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• pp.697-704
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• 1996

Quinolone derivatives, SJ5b (ethyl 5,12-dihydro-5-dihydro-5-oxobenzoxazolo[3,2-a]quinoline-6-carboxylate) and SQ7b (3-fluoro-2-(4-methylpiperazin-1-yl)-5.12-dihydro-5-oxobenzoxa zolo[3,2-a]quinoloine carboxylic acid) showed in vitro cytotoxicities against various tumor cell lines. SJ5b and SQ7b completely inhibited the DNA relaxation activities of human placental topoisomerase II at the concentration of 15.63 and 1.95 ${\mu}$g/ml, respectively. However, unlike etoposide which stabilize the topoisomerase II-DNA complex, SQ7b did not cause topoisomerase II-mediated DNA cleavage and SJ5b weakly stabilized the topoisomerase II-DNA cleavable complex. Through both experiments. DNA relaxation assay by the increment of topoisomerase II concentration and DNA unwinding assay, it was shown that SJ5b and SQ7b did not interact with topoisomerase II itself but bound to DNA. Therefore, it was concluded that DNA binding of SJ5b and SQ7b caused the inhibition of topoisomerase II related to DNA relaxation but no or very weak stabilization of topoisomerase II-DNA cleavable complex. In addition, SJ5b and SQ7b prevented whole cell nucleic acid syntheses in HL60 cells.

• Archives of Pharmacal Research
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• 제24권4호
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• pp.270-275
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• 2001

Bioisostere approach has been shown to be useful to augment potency or to modify certain physiological properties of a lead compound. Based upon well documented bioisosterism, an isosteric replacement of benzene ring of 4-hydroxy-2-quinolone compound (L-695902) with a thiophene moiety was carried out to prepare the title compounds, 4-hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b] pyrimidines 15. The resulting bioisosteric compounds 15 were evaluated for their antagonistic activity (birding assay) for NMDA receptor glycine site.

• Archives of Pharmacal Research
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• 제29권12호
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• pp.1080-1085
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• 2006

A series of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-one derivatives were synthesized using 7-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES) and the subcutaneous pentylenetetrazole test (sc-PTZ), and their neurotoxicities were measured by the rotarod neurotoxicity test (Tox). The tests demonstrated that 8-hexyloxy-4,5-dihydro-[1.2.4]triazole[4.3-a]quinoline-1-one (4e) and 8-heptyloxy-4,5-dihydro-[1,2,4]triazole[4, 3-a]quinoline-1-one (4f) were the most potent anticonvulsants, with 4e having $ED_{50}$ values of 17.17 mg/kg and 24.55 mg/kg and protective index ($PI=TD_{50}/ED_{50}$) values of 41.9 and 29.3 in the MES and sc-PTZ tests, respectively, and 4f having $ED_{50}$ values of 19.7 mg/kg and 21.2 mg/kg and PI values of 36.5 and 33.9 in the MES and sc-PTZ tests, respectively. The PI values of 4e and 4f were many fold better than that of the marketed drugs phenytoin, carbamazepine, phenobarbital and valproate, which have PI values in the range of 1.6-8.1 in the MES test and <0.22-5.2 in the sc-PTZ test. Structure-activity relationships were also discussed.

• 약학회지
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• 제45권4호
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• pp.334-338
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• 2001

A series of (-)-9-fluoro-2,3-dihydro-3(S)-methyl-10-(4-substituted-1-piperazinyl)-7-oxo-7H-pyrido [1,2,3-de] [1,4]-benzoxazine-6-carboxylic acid (5-8) was synthesized and evaluated for antibacterial activity against gram(+) and gram(-) bacteria. These synthesized compounds showed a lower activity than levofloxacin.