Chemical and Pharmaceutical Bulletin p. 1074 - 1085 (1996)
Update date:2022-08-02
Topics:
Yoshida
Yamamoto
Orita
Kakiuchi
Takahashi
Itakura
Kado
Mitani
Yasuda
Kato
Itoh
A series of 7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-1,4-dihydro-4- oxoquinoline-3-carboxylic acids bearing various substituents (H, F, Cl, Me, OH, OMe, OEt, OCH2F, OCHF2, OCF3, SMe) at the C-8 position was prepared and evaluated for in vitro antibacterial activity against both standard laboratory strains and bacteria resistant to quinolones such as ciprofloxacin (CPFX, 1) and ofloxacin (OFLX, 2) from clinical isolates. The 8-methyl (8a), 8-fluoro (9a), 8-chloro (10a) and 8-methoxy (12a) compounds were 4 times more potent than CPFX (1) against both gram-positive and gram-negative bacteria. But these four compounds caused injury to the chromosomes of mammalian cells at a concentration of 100 μg/ml. Next, a series of quinolones having various substituents (H, Cl, Me, NH2, NHMe, NMe2) at the C-5 position was prepared and evaluated for antibacterial activity and injurious effect on the chromosome. We found that the 5-amino-8-methyl compound (8d) showed strong antibacterial activity (in vitro antibacterial activity of 8d is 4 times more potent than that of CPFX (1) against both gram-positive and gram-negative bacteria), reduced injury to the chromosome, and reduced quinolone-type toxicity (free from both phototoxicity at a dosage of 30 mg/kg in guinea pigs (i.v.) and convulsion-inducing activity when coadministered with fenbufen at a dosage of 100 mg/kg in mice (i.p.)).
View MoreJiangsu Zhenfang Chemical CO.,LTD.(Suzhou Zhenfang Chemical Factory)
Contact:+86-512-69598882
Address:Room1201, Jiayuan Road No.1018, Xiangcheng District, Suzhou, China
Contact:+86+21-58956006 15800617331
Address:402 Room, 150# Cailun Road, Zhangjiang high tech park, Shanghai
ALPHA PHARMACEUTICAL CO,LTD JIANGSU
Contact:+86-527-84829968,+86-527-84829998
Address:suqian city
Contact:+86+21-58956006 15800617331
Address:402 Room, 150# Cailun Road, Zhangjiang high tech park, Shanghai
KAIYUAN CHEMICAL COMPANY LIMITED.
website:http://www.kaiyuanchem.com
Contact:+86-22-59891255/66/77
Address:B-2205, Kuangshi International Building, Yingbin Road, XiangLuo Bay Business District, Binhai New area, Tianjin, China.
Doi:10.1021/ol035365d
(2003)Doi:10.1021/jo9604292
(1996)Doi:10.1021/jm970872k
(1998)Doi:10.1016/0022-328X(95)05586-0
(1995)Doi:10.1007/s12039-020-01801-5
(2020)Doi:10.1080/1065657X.2001.10702025
(1951)