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 MoreShanghai Kangxin Chemical Co., Ltd
Contact:+86 21 60717227
Address:118,Ganbai Village,Waigang Town,Jiading District,Shanghai
Shanghai Demand Chemical Co., ltd,China
Contact:86-021-55237578/55239122
Address:Room 3H, No.578, Yingkou Road, Yangpu District, Shanghai, China
Hunan Haili Chemical Industry Co.,Ltd.
Contact:+86-731-85521860
Address:No.251, 2nd Section, Furong Road, Changsha,Hunan,China
Contact:+86-29-88710656
Address:South Tai bai Road, High Tech Development Zone, Xi'an China
Shandong Yaroma Perfumery Co., Ltd.
Contact:+86- 531- 88024598
Address:7-702 Caizhi Central, 59 Gong Ye South Road, Jinan City,250101, P. R. 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)