Synthesis and in vitro antibacterial activities of 7-(3-aminopyrrolo[3,4-c]pyrazol-5(2H,4H,6H)-yl)quinolone derivatives

Chinese Chemical Letters

Volumn 21, Issue 10, 2010, Pages 1141-1144

  Guo, Xin ^a,b   Li, Yi Liang ^a,c   Liu, Yu Fei ^d   Guo, Hui Yuan ^a   Wang, Yu Cheng ^a  

^a INSTITUTE OF MEDICINAL BIOTECHNOLOGY   (China)

^b SOUTHWEST UNIVERSITY   (China)

^c TIANJIN INSTITUTE OF PHARMACEUTICAL RESEARCH   (China)

^d XUZHOU MEDICAL UNIVERSITY   (China)

Author keywords

Antibacterial activities; Fluoroquinolone; Synthesis

Indexed keywords

EID: 77955842512     PISSN: 10018417     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cclet.2010.06.011     Document Type: Article

References (10)

1. Domagala J.M. Antimicrob. Chemother. 1994, 33:685.
2. Hooper D.C., Wolfson J.S. N. Engl. J. Med. 1991, 32:384.
3. Chu D.W., Fernandes P.B. Adv. Drug Res. 1991, 21:39.
4. Domagala J.M., Heifetz C.L., Mich T.F., et al. J. Med. Chem. 1986, 29:445.
5. Sanchez J.P., Domagala J.M., Hagen S.E., et al. J. Med. Chem. 1988, 31:983.
6. Chu D.T.W., Fernandes P.B., Caiborne A.K., et al. J. Med. Chem. 1986, 29:2363.
7. N. Takagi, H. Fubasami, H. Matukubo, EP 464823 (1992).
8. Synthesis of 1-cyclopropyl-6-fluoro-7-(3-aminopyrrolo[3,4-c]pyrazol-5(2H,4H,6H)-yl)-1,4-dihydro-4-oxo-1,8-naphthy-ridine-3-carboxylic acid (6a): a mixture of 2 (0.38g, 1.9mmol), 5 (0.53g, 1.3mmol), triethylamine (1.0mL) and anhydrous acetonitrile (10mL) was stirred at room temperature for 0.5h, and then concentrated in vacuo. To the residue was added 5% NaOH solution (6.0mL), the reaction mixture was stirred at 40°C for 0.5h and then adjusted to pH 5 with 2mol/L HCl. The precipitate was collected by suction to give off-white amorphous product 6a (0.32g, 66.5%).
9. Typical data of the synthetic compounds: 6f 1H NMR (400MHz, DMSO-d6): δ 1.00-1.18 (m, 4H), 4.05-4.09 (m, 1H), 4.57-4.60 (m, 4H), 6.88 (t, 1H), 8.63 (s, 1H), 7.87 (d, 1H), 8.75 (s, 1H); 13C NMR (400MHz, DMSO-d6): δ 9.3, 40.8, 49.5, 49.8, 107.2, 108.8, 109.1, 114.7, 117.3, 118.2, 119.9, 130.7, 135.4, 142.2, 151.2, 152.4, 154.9, 165.3, 175.7; HRMS-ESI m/z: 458.10521 (calcd. for C19H16F3N5O4Na [M+Na]+). 7f 1H NMR (400MHz, DMSO-d6): δ 1.00-1.18 (m, 4H), 3.52 (s, 3H), 4.05-4.09 (m, 1H), 4.55-4.73 (m, 4H), 6.90 (t, 1H), 7.89 (d, 1H), 8.75 (s, 1H); 13C NMR (400MHz, DMSO-d6): δ 9.3, 36.4, 40.8, 48.8, 50.6, 105.6, 107.3, 108.9, 114.7, 117.3, 118.6, 119.9, 131.0, 135.3, 137.7, 144.0, 147.4, 151.3, 165.3, 175.7; HRMS-ESI m/z: 450.13891 (calcd. for C20H19F3N5O4 [M+H]+). 7g 1H NMR (400MHz, CDCl3): δ 1.02-1.25 (m, 4H), 3.66 (s, 3H), 3.72 (s, 3H), 4.03-4.07 (m, 1H), 4.63-4.79 (m, 4H), 7.88 (d, 1H), 8.81 (s, 1H); 13C NMR (400MHz, DMSO-d6): δ 8.9, 40.9, 48.5, 50.1, 61.4, 106.0, 106.1, 106.4, 119.0, 134.2, 136.0, 136.1, 143.7, 144.5, 147.4, 150.3, 153.1, 155.6, 165.6, 176.0; HRMS-ESI m/z: 414.15776 (calcd. for C20H21FN5O4 [M+H]+). 7h 1H NMR (400MHz, CDCl3): δ 1.45-1.47 (m, 3H), 3.50 (s, 3H), 4.32-4.35 (m, 1H), 4.52-4.91 (m, 6H), 7.59 (d, 1H), 8.93 (s, 1H); 13C NMR (400MHz, DMSO-d6): δ 17.8, 36.3, 49.0, 50.6, 54.8, 67.9, 103.5, 106.2, 117.5, 124.9, 130.0, 137.6, 144.6, 146.1, 147.3, 152.5, 154.9, 166.1, 176.0; HRMS-ESI m/z: 400.14211 (calcd. for C19H19FN5O4 [M+H]+).
10. MICs were determined as described by the NCCLS (see National Committee for Clinical Laboratory Standards (2001). Performance standards for antimicrobial susceptibility testing: 11th informational supplement, vol. 21, M100-S11. National Committee for Clinical Laboratory Standards, Wayne, PA). The MIC was defined as the lowest concentration of each compound resulting in inhibition of visible growth of bacteria after incubation at 37°C for 18-24h.