Synthesis, antimycobacterial and antibacterial activity of 1-(6-amino-3,5-difluoropyridin-2-yl)fluoroquinolone derivatives containing an oxime functional moiety

Article abstract of DOI:10.1016/j.bmcl.2016.03.050

A series of novel 1-(6-amino-3,5-difluoropyridin-2-yl)fluoroquinolone derivatives containing an oxime functional moiety were synthesized and evaluated for their biological activity. Our results reveal that compounds 9a-9c have considerable activity against both of MTB H37Rv ATCC 27294 (MICs: 3.81-7.13 μg/mL) and methicillin-sensitive Staphylococcus aureus strains (MICs: <0.008-0.5 μg/mL).

Full text of DOI:10.1016/j.bmcl.2016.03.050

Accepted Manuscript
Synthesis, antimycobacterial and antibacterial activity of 1-(6-amino-3,5-di-
fluoropyridin-2-yl)fluoroquinolone derivatives containing an oxime functional
moiety
Ju Huang, Minghua Wang, Bin Wang, Zhaoyang Wu, Mingliang Liu, Lianshun
Feng, Jun Zhang, Xiaoning Li, Yang Yang, Yu Lu
PII:
S0960-894X(16)30270-0
DOI:
http://dx.doi.org/10.1016/j.bmcl.2016.03.050
BMCL 23693
Reference:
Bioorganic & Medicinal Chemistry Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
24 December 2015
2 March 2016
14 March 2016
Please cite this article as: Huang, J., Wang, M., Wang, B., Wu, Z., Liu, M., Feng, L., Zhang, J., Li, X., Yang, Y.,
Lu, Y., Synthesis, antimycobacterial and antibacterial activity of 1-(6-amino-3,5-difluoropyridin-2-
yl)fluoroquinolone derivatives containing an oxime functional moiety, Bioorganic & Medicinal Chemistry
Letters (2016), doi: http://dx.doi.org/10.1016/j.bmcl.2016.03.050
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Synthesis, antimycobacterial and antibacterial activity of
1-(6-amino-3,5-difluoropyridin-2-yl)fluoroquinolone derivatives
containing an oxime functional moiety
Ju Huang a, 1, Minghua Wang a, 1, Bin Wang c, Zhaoyang Wu a, Mingliang Liu a, *,
Lianshun Feng a, Jun Zhang a,b, Xiaoning Li a, Yang Yang a, Yu Lu c,*
a
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking
Union Medical College, Beijing 100050, China
b
c
Zhejiang Starry Pharmaceutical Co. Ltd., Xianju 317300, China
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of
Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest
Hospital, Capital Medical University, Beijing 101149, China
Abstract: A series of novel 1-(6-amino-3,5-difluoropyridin-2-yl)fluoroquinolone
derivatives containing an oxime functional moiety were synthesized and evaluated for
their biological activity. Our results reveal that compounds 9a-9c have considerable
activity against both of MTB H37Rv ATCC 27294 (MICs: 3.81 - 7.13 μg/mL) and
methicillin-sensitive S. aureus strains (MICs: < 0.008 - 0.5 μg/mL).
Key words: Fluoroquinolone derivatives; Synthesis; Antimycobacterial activity;
Antibacterial activity
Since the discovery of norfloxacin in the early 1980s, fluoroquinolone (FQ)
antibacterial agents which target two type II bacterial topoisomerase enzymes, DNA
gyrase and / or topoisomerase IV, have been among the most attractive drugs in the
anti-infective chemotherapy field.1 Some of them, such as ciprofloxacin (CPFX),
ofloxacin and levofloxacin (LVFX) are frequently used as second-line drugs for the
treatment of tuberculosis (TB) including multi-drug resistant TB (MDR-TB).2
*Corresponding author. Tel./fax:+86 10 63036965. E-mail addresses: lmllyx@126.com(M. Liu),
luyu4876@hotmail.com (Y. Lu).
1These authors contributed equally to this work.

However, FQ resistance increases in almost all Gram-negative and Gram-positive
species as well as M. tuberculosis (MTB), due mainly to the high level of use and to
some degree of abuse.3 The ideal strategy to such challenges is to find novel agents
that inhibit new targets in pathogens, but a more practical approach is to modify the
structures of existing antibacterial agents to increase potency and to overcome
resistance.4
FQs consist of a 4-quinolone / naphthyridone-3-carboxylic acid core and a
secondary amino group attached to the C-7 position of the heterocyclic core. CPFX,
LVFX, moxifloxacin and gemifloxacin (GMFX, Fig. 1) represent the most common
cores of important FQs on the market. The basic substituent at C-7 position, playing
an important role in the antibacterial potency, spectrum and safety of FQs,1 is
recognized as the most adaptable site for chemical change, and the presence of five-
or six-membered nitrogen heterocycle including pyrrolidine, piperazine and
piperidine at this position is particularly structural feature of FQs.5
Recently, some new FQs with novel cores different from the traditional ones, such
as sitafloxacin, delafloxacin (DLFX, ABT-492) and AM-1954, have been reported.
On the other hand, methyloxime-functionalized pyrrolidines as novel C-7 substituents
have attracted great attention and led to the discovery of new FQs (GMFX,
zabofloxacin and DW286).6-8 In our previous works which have been published, some
FQs containing oxime-functionalized azetidines, pyrrolidines or piperidines were
found to have considerable biological activity.9-15 These studies suggest the
importance of the oxime functional group with respect to biological activity and
pharmacokinetic profiles of FQs.
In our continuous program in the search of potent and safe FQ derivatives, we
intended to make structural modifications on DLFX (Fig. 1) which is in phase III
clinical trials currently,16 a broad-spectrum FQ antibiotic possessing excellent activity
against many MDR-Gram-positive organisms,17-19 by introduction of a four-, five- or
six-membered nitrogen heterocyclic amine moiety with various alkyloxime groups
instead of the 3-hydroxyazetidin-1-yl one at the 7 position (Fig. 1). Thus, a series of
novel
1-(6-amino-3,5-difluoropyridin-2-yl)FQ
derivatives
with
an
(R)

/(S)-3-alkoxyimino-2-aminomethylazetidyl,3-alkoxyimino-4-aminomethyl-(4-methyl)
pyrrolidyl or 3-alkoxyimino-4-amino(hydroxyl)piperidyl group at the C-7 position
were designed, synthesized and evaluated for their biological activity in this study.
Our primary objective was to optimize the potency of these compounds against
clinically important pathogens (especially Gram-positive ones) and MTB including
MDR-MTB. A preliminary SAR study is also explored to facilitate the further
development of FQs.
Figure 1. Design of novel fluoroquinolone derivatives
Detailed synthetic pathways to novel naphthyridinone derivatives 9a-9n and
quinolone derivatives 11a, 11k are depicted in Scheme 1. Enol ethers (5a, 5b) were
conveniently obtained from the carboxylic acid 1a, 1b by chloroformylation (2a, 2b),
condensation with diethyl malonate (3a, 3b), partial hydrolysis followed by
decarboxylation (4a, 4b) and condensation with triethylorthoformate in acetic
anhydride
successively.
Nucleophilic substitution
of
5a,
5b
with
3,5-difluoropyridine-2,6-diamine in NMP and then base-assisted cyclization of the
resulted enamino ethers 6a, 6b in butanone afforded core esters (7a, 7b) according to
well established procedures. 13, 20-25
Naphthyridone derivatives 9a-9n were easily prepared through direct condensation
of the carboxylic acid 8a which was obtained by hydrolysis of the corresponding core
ester 7a, with various side chain compounds (RH) in the presence of Et3N.14,15
However, direct condensation of the quinolone acid 8b obtained from the ester 7b,
with RH turned out to be rather complicated and the products were difficult to purify.
After various attempts, quinolone derivatives 11a,11k were successfully obtained

from 7b by condensation with RH in the presence of LiBr and DBU and then
24
hydrolysis of the condensates 10a, 10k
(Scheme 1). All of the new synthetic
compounds were well characterized by 1 H NMR, MS and HRMS.
Scheme 1. Synthesis of quinolone / naphthyridinone derivatives 9, 11
The target compounds 9, 11 were initially evaluated for their in vitro activity
against MTB H37Rv ATCC 27294 using the Microplate Alamar Blue Assay
(MABA).26, 27 The minimum inhibitory concentration (MIC) is defined as the lowest
concentration effecting a reduction in fluorescence of ≥ 90% relative to the mean of
replicate bacterium-only controls and MICs of these compounds along with CPFX,
LVFX, isoniazid (INH) and rifampicin (RFP) for comparison are presented in Table 1.

The data reveals that all of the new synthesized compounds 9, 11 (MICs: 3.81 -> 32
μg/mL) are much less than the four reference drugs (MICs: 0.25 - 0.05 μg/mL), but
the most active compounds 9a-9c have promising activity with MICs of 7.13, 6.56
and 3.81 μg/mL, respectively, against this strain. In addition, our results suggest that
simply increasing the lipophilicity which is expressed in the term of their Clog P
values (Table 1) can improve the anti-MTB activity of FQs with similar structures (9a
vs 9b vs 9c), which is consistent with the SAR in Sriram’s study.28
Table 1. Structures, physical data and antimycobacterial activity of compounds 9, 11
9, 11
MIC (μg/mL)
Compd.
R
X
m.p. [C]a
Clog Pb
MTB
N
N
N
>250
>250
>250
1.52
1.86
3.26
7.13
9a
9b
9c
6.56
3.81
N
157-159
3.96
15.59
9d
N
N
N
N
>250
>250
1.12
1.45
2.85
1.12
>32
>32
>32
>32
9e
9f
220-222
>250
9g
9h

N
N
>250
>250
1.45
2.85
>32
>32
9i
9j
N
N
N
234-236
202-204
220-222
1.66
3.39
2.04
>32
>32
9k
9l
30.74
9m
N
138-140
179-181
157-159
3.77
1.99
2.12
>32
30.52
>32
9n
C-Cl
C-Cl
11a
11k
CPFX
LVFX
INH
1.32
1.35
0.25
0.25
0.05
0.05
RFP
a
b
Melting points are uncorrected ;
The Clog P is calculated by Chemoffice 2010
software; CPFX: Ciprofloxacin ; LVFX: Levofloxacin ; INH: Isoniazid; RFP: Rifampicin;
MTB: MTB H37Rv ATCC 27294.
The target compounds 9, 11 were also evaluated for their in vitro antibacterial
activity against representative strains using standard techniques.29 Minimum
inhibitory concentration (MIC) is defined as the concentration of the compound
required to give complete inhibition of bacterial growth, and MICs of 9, 11 against
Gram-negative and Gram-positive strains along with moxifloxacin (MXFX) and
LVFX for comparison, are listed in Tables 2 and 3, respectively. These data suggest
that some of the target compounds 9, 11 have considerable potency against

Gram-positive strains, although they are generally less active than the reference drugs
MXFX and LVFX against the Gram-negative strains with a few exceptions. For
example, compounds 9a-9c and 11a,11k show excellent potency in inhibiting the
growth of methicillin-sensitive S. aureus (MSSA) (MICs: < 0.008 - 0.5 μg/mL, four
strains) (Table 3). It is noted that compound 11a also has good activity against
clinically important pathogens Pseudomonas aeruginos (MICs: 4 - 8 μg/mL, six
strains) which is comparable to MXFX (MICs: 1 - 16 μg/mL) (Table 2).

Table 2. In vitro antibacterial activity of compounds 9, 11 against Gram-negative strains
Compd
Strains MIC (μg /mL)
E.coli
2
E.co.1
16
E.co.2
>128
E.co.3
128
E.co.4
128
K.p.1
128
K.p.2
32
K.p.3
K.p.4
K.p.5
>128
K.p.6
>128
K.p.7
>128
P.a.
4
P.a.1
16
P.a.2
32
P.a.3
32
P.a.4
32
P.a.5
64
9a
9b
>128
>128
0.5
0.5
16
2
8
8
128
128
64
64
64
32
32
128
128
64
128
128
128
128
128
128
4
16
32
16
32
16
32
16
32
32
32
9c
128
128
64
128
8
9d
64
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
64
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
64
128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
32
>128
64
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
64
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
16
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
64
>128
>128
128
128
16
16
64
64
128
128
128
128
128
128
4
128
32
128
64
128
64
128
32
128
32
9e
64
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
64
9f
2
64
64
32
64
64
64
64
9g
4
64
128
64
>128
>128
>128
>128
>128
>128
>128
>128
128
128
64
128
64
128
64
128
64
28
9h
16
16
8
>128
>128
128
>128
128
64
64
9i
>128
128
>128
>128
>128
>128
16
128
128
128
128
128
128
8
128
128
128
128
128
128
8
128
128
128
128
128
128
8
128
128
128
128
128
128
8
128
128
128
128
128
128
8
9j
9k
16
64
64
16
0.125
1
9l
9m
9n
128
2
11a
11k
MXFX
LVFX
128
64
>128
16
>128
8
>128
16
>128
8
128
1
>128
64
>128
8
>128
32
>128
16
16
2
64
64
64
128
8
128
1
0.06
0.125
2
4
16
16
2
8
4
4
4
1
64
16
8
16
8
1
1
2
2
2
2
E.coli: E. coli ATCC 25922. E.co.1: Extended-spectrum β-lactamase-producing (ESBL+) E. coli 14-1. E.co.2: ESBL+ E. coli 14-2. E.co.3: E. coli 14-1. E.co.4: E. coli 14-2. K.p.1: ESBL+ K. pneumoniae 14-17. K.p.2:
ESBL+ K. pneumoniae 14-18. K.p.3: ESBL+ K. pneumoniae 14-19. K.p.4: K. pneumoniae 14-1. K.p.5: K. pneumoniae 14-2. K.p.6: K. pneumoniae 14-3. K.p.7: K. pneumoniae 14-4. P.a.: P. aeruginosa ATCC 27853.
P.a.1: P. aeruginosa 14-9. P.a.2: P. aeruginosa 14-14. P.a.3: P. aeruginosa 14-15. P.a.4: P. aeruginosa 14-16. P.a.5: P. aeruginosa 14-19. MXFX: Moxifloxacin. LVFX: Levofloxacin.

Table 3. In vitro antibacterial activity of compounds 9, 11 against Gram-positive strains
Compd
Strains
MIC (μg/mL)
S.a.
0.5
MSSA1 MSSA2 MSSA3 MRSA1 MRSA2 MSSE1 MSSE2 MSSE3 MRSE1 MRSE2 MRSE3
S.p.
64
E.fm.1
>128
E.fm.2
64
E.fs. 1 E.fs. 2 E.fs. 3
0.5
0.25
0.015
0.25
8
0.5
0.25
0.5
0.25
4
>128
64
64
64
>128
64
64
32
64
32
64
32
128
64
64
16
16
16
9a
9b
32
0.06
0.5
32
16
16
128
128
8
16
8
16
32
<0.008
0.25
64
128
64
64
32
32
16
32
32
8
16
9c
16
0.25
4
8
64
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
64
>128
64
>128
64
64
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
64
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
32
32
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
32
>128
>128
>128
>128
>128
>128
>128
>128
128
>128
>128
16
>128
>128
>128
>128
>128
>128
>128
>128
128
9d
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
32
8
4
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
128
>128
>128
>128
>128
>128
>128
>128
>128
128
>128
128
>128
8
>128
>128
>128
>128
>128
>128
>128
>128
>128
>128
64
64
128
32
32
64
128
32
64
64
64
32
8
9e
2
4
8
4
64
128
>128
>128
>128
>128
>128
>128
>128
>128
64
32
9f
2
2
4
32
4
>128
>128
>128
>128
>128
>128
>128
>128
32
64
9g
16
16
4
32
16
32
4
128
64
9h
32
32
9i
4
8
64
9j
8
8
8
16
8
64
9k
8
8
4
64
9l
2
2
4
4
64
>128
>128
64
9m
9n
2
4
4
4
32
0.03
0.5
0.06
0.125
0.06
0.5
0.06
0.25
0.125
0.25
<0.008
0.125
0.25
0.5
<0.008
0.5
16
11a
11k
MXFX
LVFX
>128
12
>128
32
128
2
128
2
>128
8
>128
8
>128
8
64
16
0.5
1
>128
8
>128
16
>128
8
0.015
0.5
64
8
128
1
2
32
64
64
128
16
32
64
S.a.: S. aureus CMCC 26003. MSSA1: Methicillin-sensitive S. aureus 14-2. MSSA2: Methicillin-sensitive S. aureus 14-3. MSSA3: Methicillin-sensitive S. aureus 14-4. MRSA1: Methicillin-resistant S.
aureus 14-4. MRSA2: Methicillin-resistant S. aureus 14-5. MSSE1: Methicillin-sensitive S. epidermidis 14-2. MSSE2: Methicillin-sensitive S.epidermidis 14-4. MSSE3: Methicillin-sensitive S. epidermidis
14-6. MRSE1: Methicillin-resistant S.epidermidis 14-22. MRSE2: Methicillin-resistant S. epidermidis 14-37. MRSE3: Methicillin-resistant S.epidermidis 14-39. S.p.: S. pneumoniae ATCC 19615. E. fm. 1:
E. faecium 14-1. E. fm. 2: E. faecium 14-2. E. fs. 1: E. faecalis 14-1. E. fs. 2: E. faecalis 14-2. E. fs. 3: E. faecalis 14-3. MXFX: Moxifloxacin. LVFX: Levofloxacin.

In the case of Gram-positive MSSA (four strains), the activity of the
1-(6-amino-3,5-difluoropyridin-2-yl) FQs in this study is closely related to both of the
groups at the 7- and 8-positions. In the series of naphthyridinone derivatives 9a-9n,
the sizes of the heterocycles and alkyl groups of the oxime moiety at the 7-position
are especially important for the activity. Pyrrolidyl-based derivatives (9a-9c) are
generally more active than azetidyl- and piperidinyl-based ones with the same alkyl
group. The contribution of the alkyl groups is as follows: benzyl > ethyl > methyl for
pyrrolidyl-based ones (9a-9c), which suggest that simply increasing the lipophilicity
could improve the antibacterial activity. However, introduction of an additional
methyl group at C-3 of the pyrrolidyl moiety significantly reduces the activity (9c vs
9d). It is interesting that piperidinyl-based derivatives are much less active than the
corresponding pyrrolidyl-based ones (9a vs 9k, 9c vs 9l), but replacement of the
amino group of the piperidinyl moiety leads to improved activity (9k vs 9m, 9l vs 9n).
Moreover, the chirality at C-2 of the azetidinyl group of the target compounds
influences the activity, and the R enantiomers are more active than the corresponding
S ones (9e vs 9h, 9f vs 9i, 9g vs 9j). On the other hand, the activity of the group at the
8-position is in the order: C-Cl ≥ N (9a vs 11a) when a pyrrolidine served as the C-7
side chain, and C-Cl >> N (9k vs 11k) for the piperidinyl-based derivatives.
In summary, a series of novel 1-(6-amino-3,5-difluoropyridin-2-yl) FQ derivatives
containing a four-, five- or six-membered nitrogen heterocyclic amine moiety with
various alkyloxime groups at the C-7 position were designed, synthesized and
evaluated for their biological activity. Our results reveal that compounds 9a-9c have
promising activity against MTB H37Rv ATCC 27294 (MICs: 3.81 - 7.13 μg/mL). On
the other hand, compounds 9a-9c and 11a, 11k possess excellent in vitro activity
against all of the MSSAs (MICs: < 0.008 - 0.5 μg/mL, four strains). In addition, our
results suggest that the lipophilicity seems to be an important parameter affecting both
the anti-MTB and antibacterial activity.
Acknowledgments

This work was supported by the National S&T Major Special Project on Major
New Drug Innovations (2014ZX09507009-003), NSFC 81373267-003 and Beijing
Municipal Administration of Hospitals Clinical Medicine Development of Special
Funding Support (ZYLX201304).
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29. MIC values were determined as described by the NCCLS (see: National Committee for
Clinical Laboratory Standards, Performance Standards for Antimicrobial Susceptibility
Testing: 11th Informational Supplement, vol. 21; NCCLS: Wayne, PA, USA, 2001,
M100-S11). MIC was defined as the lowest concentration of each compound that inhibits
visible growth of bacteria after incubation at 35C for 18-24 h.
30. Compound 9a, off-white solid (23.1%), m.p. >250℃. 1H NMR (400 MHz, DMSO-d6) δ 8.81
(1H, s, C2-H), 8.05 (1H, d, J = 12.0 Hz, C5-H), 7.93 - 7.89 (1H, m), 4.29 (2H, s), 3.90 (2H, s),
3.78 (3H, s, O-CH3), 2.97 (1H, brs), 2.79 - 2.64 (2H, m). MS-ESI (m/z): 478.28(M+H)+.
HRMS-ESI (m/z): Calcd. for C24H23O4N4F2(M+H)+: 478.14451; Found: 478.14398.
Compound 9b, off-white solid (18.9%), m.p. >250℃. 1H NMR (400 MHz, DMSO-d6) δ 8.89
(1H, s, C2-H), 8.10 (1H, d, J = 12.0 Hz, C5-H), 7.95 - 7.89 (1H, m), 4.24 (2H, s), 4.06 (2H, q,
J = 8.0 Hz), 3.90 (2H, s), 3.08 (1H, s), 2.79 - 2.64 (2H, m), 1.20 (3H, t, J = 8.0 Hz). MS-ESI
(m/z): 492.25(M+H)+. HRMS-ESI (m/z): Calcd. for C24H23O4N4F2(M+H)+: 492.16016;
Found: 492.15945. Compound 9c, off-white solid (22.4%), m.p. >250℃. 1H NMR (400 MHz,
DMSO-d6) δ 8.91 (1H, s, C2-H), 8.16 (1H, d, J = 12.0 Hz, C5-H), 7.82-7.75 (1H, m), 7.43 -
7.36 (5H, m, OCH2-Ar), 5.15 (2H, s, O-CH2Ar), 4.28 (4H, m), 3.13 - 3.07 (3H, m). MS-ESI
(m/z): 554.33(M+H)+. HRMS-ESI (m/z): Calcd. for C24H23O4N4F2(M+H)+: 554.17581;
Found: 554.17515. Compound 11a, off-white solid (17.3%), m.p. 179 - 181℃. 1H NMR (400
MHz, DMSO-d6) δ 8.74 (1H, s, C2-H), 8.02 (1H, d, J = 12.0 Hz, C5-H), 7.97 - 7.92 (1H, m),
3.93 (2H, s), 3.80 (1H, brs), 3.76 (3H, s, O-CH3), 3.66 (1H, brs), 3.53 (1H, brs), 3.27 - 3.20
(2H, m). MS-ESI (m/z): 511.34 (M+H)+. HRMS-ESI (m/z): Calcd. for C21H19O4N6ClF3
(M+H)+: 511.11011; Found: 511.11029. Compound 11k, off-white solid (21.2%), m.p. 157 -
159℃. 1H NMR (400 MHz, DMSO-d6) δ 8.77 (1H, s, C2-H), 8.07 (1H, d, J = 12.0 Hz, C5-H),
7.99 (1H, brs), 5.12 - 5.06 (1H, m), 3.71 (3H, s), 3.54 (1H, brs), 3.37 (2H, brs), 3.30 - 3.21
(1H, m), 3.14 - 2.95 (2H, m). MS-ESI (m/z): 511.02(M+H)+. HRMS-ESI (m/z): Calcd. for
C24H23O4N4F2(M+H)+: 511.11029; Found: 511.11236.

Synthesis, antimycobacterial and antibacterial activity of
1-(6-amino-3,5-difluoropyridin-2-yl)fluoroquinolone derivatives
containing an oxime functional moiety
Ju Huang a, 1, Minghua Wang a, 1, Bin Wang c, Zhaoyang Wu a, Mingliang Liu a, *,
Lianshun Feng a, Jun Zhang a,b, Xiaoning Li a, Yang Yang a, Yu Lu c,*
A series of novel 1-(6-amino-3,5-difluoropyridin-2-yl)fluoroquinolone derivatives
containing an oxime functional moiety were synthesized and evaluated for their
biological activity. Our results reveal that compounds 9a-9c have considerable
activity against MTB H37Rv ATCC 27294 (MICs: 3.81 - 7.13 μg/mL) and
methicillin-sensitive S. aureus strains (MICs: < 0.008 - 0.5 μg/mL).
*Corresponding author. Tel./fax:+86 10 63036965. E-mail addresses: lmllyx@126.com(M. Liu),
luyu4876@hotmail.com (Y. Lu).
1These authors contributed equally to this work.