Synthesis and biological evaluation of 2-phenyl-4-aminoquinolines as potential antifungal agents

Article abstract of DOI:10.1007/s11030-019-10012-1

Abstract: A series of 2-phenyl-4-aminoquinolines were designed, synthesized and evaluated for their antifungal activities against three phytopathogenic fungi in vitro. All of the target compounds were fully elucidated by ¹H NMR, ¹³C

Full text of DOI:10.1007/s11030-019-10012-1

Molecular Diversity
https://doi.org/10.1007/s11030-019-10012-1
ORIGINAL ARTICLE
Synthesis and biological evaluation of 2‑phenyl‑4‑aminoquinolines
as potential antifungal agents
Rui Yang1 · Wenhao Du1 · Huan Yuan1 · Tianhong Qin1 · Renxiao He1 · Yanni Ma2 · Haiying Du3
Received: 13 August 2019 / Accepted: 2 November 2019
© Springer Nature Switzerland AG 2019
Abstract
A series of 2-phenyl-4-aminoquinolines were designed, synthesized and evaluated for their antifungal activities against
three phytopathogenic fungi in vitro. All of the target compounds were fully elucidated by 1H NMR, 13C NMR and HRMS
spectra. The results indicated that most of the target compounds demonstrated signifcant activities against the tested fungi.
Among them, compound 6e exhibited more promising inhibitory activities against C. lunata (EC50 =13.3 μg/mL), P. grisea
(EC50 =14.4 μg/mL) and A. alternate (EC50 =15.6 μg/mL), superior to azoxystrobin, a commercial agricultural fungicide.
The structure–activity relationship (SAR) revealed that the aniline moiety at position 4 of the quinoline scafold played a
key role in the potency of a compound. And the substitution positions of the aniline moiety signifcantly infuenced the
activities. These encouraging results yielded a variety of 2-phenylquinolines bearing an aniline moiety acting as promising
antifungal agents.
Graphic abstract
Keywords 4-Aminoquinoline · Phytopathogenic fungi · Antifungal activity · Structure–activity relationship
Introduction
Electronic supplementary material The online version of this
Phytopathogenic fungi have long been known as a severe
article (https://doi.org/10.1007/s11030-019-10012-1) contains
threat to plant species. They cause serious economic loss
to global agricultural production and even lead to food
safety problem due to the mycotoxins produced by some
kinds of fungi [1, 2]. Although some agricultural antifungal
agents are currently available on the market, there is still an
extremely urgent demand for new fungicides on account of
some inevitable defects of the traditional antifungal agents,
including toxicity to non-target organisms, high residue,
growing resistance and so on [3, 4].
supplementary material, which is available to authorized users.
* Rui Yang
yangrui15@cdut.edu.cn
* Haiying Du
diane201109@126.com
1
College of Materials, Chemistry & Chemical Engineering,
Chengdu University of Technology, Chengdu 610059,
People’s Republic of China
2
Key Laboratory of Natural Products, Henan Academy
Quinoline and its derivatives, a class of important bio-
active natural products, usually serve as a core fragment
in a variety of active molecules, which exhibit extensive
of Sciences, Zhengzhou 450002, People’s Republic of China
3
College of Environment, Chengdu University of Technology,
Chengdu 610059, People’s Republic of China
Vol.:(0123456789)
1 3

Molecular Diversity
biological activities [5–12], including antifungal property
[13–16]. Over the past decades, some agricultural chemi-
cals containing a quinoline moiety have been put on the
market, such as the fungicides quinoxyfen and tebufoquin,
the insecticide fometoquin and the herbicide quinclorac. Of
note, a growing number of investigations have been directed
toward the modifcation of 2-phenylquinoline and 4-amino-
quinoline due to their versatile biological activities, such as
antimicrobial [17–19], antiviral [20, 21], antimalarial [22,
23], antitumor [24, 25] and antifungal activities [26–29]. As
shown in Fig. 1, some reported antifungal agents contain-
ing 2-phenylquinoline or 4-aminoquinoline were listed. In
previous work, we also found that some 2-phenyl-4-thio-
quinolines exhibited moderate to good antifungal activities
[30]. Nevertheless, to our best knowledge, the preparation
and antifungal activity of 2-phenyl-4-aminoquinolines were
less studied.
Results and discussion
Chemistry
As outlined in Scheme 1, o-aminoacetophenone 1 was cou-
pled to benzoyl chloride 2 in the presence of base (TEA)
to give 3 in quantitative yield. Aldol condensation of inter-
mediate 3 aforded quinolinone 4 in 94% yield, which was
then converted into 4-chloroquinoline 5 in 64% yield using
phosphorus oxychloride in refuxing dioxane. Finally, the
target compounds were smoothly generated in moderate to
good yields (28–93%) by reaction of 4-chloroquinoline 5
with amine, amide or 1,2,4-triazolylsodium under suitable
conditions [31, 32].
All target compounds were fully characterized by means
1
of H NMR, 13C NMR and HRMS spectra. Taking com-
pound 6o (R = 4′-CH3) as a representative example, two
downfeld proton signals were found at 14.35 and 11.18 ppm
in DMSO-d6, which proved that imine was transformed into
a form of hydrochloride. A singlet appeared at 6.91 ppm was
attributed to H-3 resonance of quinoline skeleton. Addition-
ally, CH3 protons occurred as a singlet at 2.41 ppm. The
other signals (13H) appeared in the range of 8.95–7.39 were
attributed to Ar–H. Due to the infuence of symmetry, eight-
een signals, including four overlapped peaks, were observed
in the 13C NMR spectrum. Finally, high-resolution mass
spectrum (HRMS) of 6o displayed a characteristic ion peak
at m/z=311.1526, which was attributed to the chemical spe-
cies of [M-Cl]+.
Inspired by the above considerations and as part of our
continuing eforts to achieve high-efcacy and broad-spec-
trum fungicides, herein we have designed and synthesized a
series of 2-phenyl-4-aminoquinolines as potential antifungal
agents by incorporation of 2-phenylquinoline and 4-amino-
quinoline in one molecule (Scheme 1). Quinolines 6a–6u
contain various substituted aniline at position 4 of quino-
line scafold, while quinolines 7, 8 carry a dimethylamine or
1,2,4-1H-triazole at position 4, respectively. And all synthe-
sized compounds were investigated for their antifungal activ-
ities against some common phytopathogenic fungi in vitro.
Fig. 1 Structures of some
promising antifungal agents
containing 2-phenylquinoline or
4-aminoquinoline
1 3

Molecular Diversity
Chemistry
Scheme 1 General synthetic route of target compounds
azoxystrobin (EC50 = 72.5 μg/mL) against C. lunata, at
least twelve compounds exhibited superior potency with
EC50 values of 13.3–48.7 μg/mL. It was worth noting that
the EC50 values of compounds 6e, 6i and 6k were lower
than 16 μg/mL against C. lunata. For P. grisea, all thirteen
tested compounds showed good activities with EC50 val-
ues of 14.4–44.2 μg/mL, and 6e exhibited the best activity
with an EC50 value of 14.4 μg/mL, superior to azoxystrobin
(EC50 = 34.5 μg/mL). Regarding A. alternate, the twelve
tested compounds also displayed good activities with EC50
values of 15.6–49.8 μg/mL. Interestingly, compounds 6e
(EC50 = 15.6 μg/mL) and 6j (EC50 = 16.9 μg/mL) showed
comparable inhibitory potency compared with azoxystrobin
(EC50 =16.0 μg/mL).
Antifungal activity
All the target compounds (6a–6u, 7 and 8), as well as
azoxystrobin (a commercial fungicide), were evaluated for
their antifungal activities in vitro against three phytopatho-
genic fungi (C. lunata, P. grisea and A. alternate) at 100
and 50 μg/mL based on mycelium growth rate method. As
described in Table 1, more than half of the target compounds
exhibited comparable or better inhibition activities at 100
and 50 µg/mL, relative to the positive control. Especially,
compounds 6a, 6b, 6e, 6i, 6j, 6o and 6r revealed better
potency with inhibition rates over 65% at 50 μg/mL in most
cases.
In order to more reliably explore the antifungal poten-
tial and structure–activity relationship (SAR), compounds
with inhibition rates over 50% at 50 μg/mL were selected
to obtain their EC50 (half maximal effective concentra-
tion) values (Table 2). As summarized in Table 2, most
compounds displayed good antifungal activities against
the tested fungi. Compared with the positive control
In case of anilinoquinolines 6a–6u, it was clearly seen
that different substituents on the aniline moiety had a
remarkable efect on the inhibitory activity. First, it was
apparent that the one bearing a para-substituent on the
aniline moiety was more potent than ortho- or meta-sub-
stituted analogs (see compounds 6e, 6h, 6j, 6l, 6o and 6r).
1 3

Molecular Diversity
Table 1 Substitution patterns and preliminary antifungal activities of target compounds
Compounds
No.
Average inhibition rate SD (%)a
C. lunata
P. grisea
A. alternate
R
100 μg/mL
50 μg/mL
100 μg/mL
50 μg/mL
100 μg/mL
50 μg/mL
6a
H
4′-F
3′-F
2′-F
4′-Cl
3′-Cl
2′-Cl
4′-Br
3′-Br
4′-I
3′-I
4′-CF3
3′-CF3
2′-CF3
4′-Me
3′-Me
2′-Me
78.3 1.5
86.1 1.8
58.1 0.8
52.5 1.6
71.7 1.5
58.8 1.2
55.8 1.0
64.1 0.7
76.7 0.4
61.9 1.0
84.1 1.4
62.3 1.0
38.1 0.5
60.9 0.3
77.6 0.5
54.3 1.7
68.9 1.2
89.6 0.8
56.5 1.3
40.6 0.4
49.7 4.5
40.7 0.7
23.1 1.7
55.5 1.5
69.6 2.2
70.8 2.2
46.4 1.4
37.9 0.6
65.0 0.3
41.7 1.4
49.0 0.0
56.5 1.0
66.4 1.8
54.7 0.7
74.8 0.4
53.9 1.7
25.5 0.0
53.8 0.5
65.3 1.2
44.4 1.0
53.4 1.0
75.6 1.4
22.6 0.2
34.3 0.3
40.6 1.5
34.3 0.2
16.7 1.3
44.9 0.0
76.1 2.0
77.7 0.9
71.4 0.5
36.6 0.3
84.5 1.4
67.6 0.8
51.9 0.4
72.5 0.8
82.6 1.0
74.1 0.8
69.9 0.7
71.1 1.5
28.8 1.2
59.7 0.9
80.1 0.2
59.3 1.2
67.3 0.7
87.0 0.9
58.8 1.1
30.0 0.3
52.9 2.9
41.5 0.5
32.7 1.2
57.0 1.6
61.5 1.6
59.3 1.5
62.4 0.5
23.9 1.1
77.2 0.8
57.5 0.5
36.9 1.7
64.8 1.5
70.5 1.6
66.3 0.8
57.7 1.1
60.9 1.1
21.5 0.7
47.2 1.0
66.0 1.2
46.0 2.0
54.0 0.9
77.5 1.5
30.2 1.3
21.1 0.7
39.6 1.8
29.6 0.3
29.3 1.2
52.9 1.0
76.6 2.0
88.1 0.4
70.3 0.9
54.6 1.8
82.6 1.7
63.3 1.0
64.7 1.0
69.0 0.8
68.3 1.6
73.2 1.4
56.3 0.9
75.4 0.6
39.6 1.1
66.5 0.3
83.1 1.1
57.4 0.4
60.2 1.3
87.5 0.9
56.9 2.3
31.4 1.0
63.7 1.8
39.9 1.0
36.8 1.9
58.7 1.4
68.1 0.6
68.1 2.3
60.7 1.1
46.2 2.1
76.3 0.2
52.6 1.1
53.9 0.6
59.5 0.8
48.5 0.5
65.8 0.8
49.4 2.0
64.9 0.7
30.4 1.3
51.4 1.4
68.1 1.6
44.9 1.5
42.0 1.8
77.4 2.1
24.3 1.1
18.6 1.2
31.2 1.5
21.8 0.8
20.0 0.9
54.7 0.5
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
6o
6p
6q
6r
4′-OMe
3′-OMe
2′-OMe
3′,5′-diOMe
dimethylamine
1,2,4-1H-triazole
6s
6t
6u
7
8
Azoxystrobin
a Average of three trials
In addition, compounds bearing substituents at ortho posi-
tion of the aniline ring were the least active compounds
followed by meta-substituted counterparts in most cases,
implying that steric bulk has in general a negative efect
on potency. For example, Compound 6e (4′-Cl) displayed
the most potent antifungal activities in the set against C.
lunata (EC50 =13.3 μg/mL), P. grisea (EC50 =14.4 μg/mL)
and A. alternate (EC50 =15.6 μg/mL). This compound was
also found to be most potent among all target compounds
investigated in the current work. Meanwhile, the above
mentioned pattern of a decreased activity from meta (EC50
of 6f: ≥ 50, 34.7, 40.5 μg/mL, respectively) to ortho sub-
stitution (6g:≥50,≥50, 41.4 μg/mL, respectively) applied.
Similar cases could easily be found elsewhere, such as com-
pounds 6b vs 6d, 6h vs 6i, 6j vs 6k and 6r vs 6s, 6t. Fur-
thermore, the type of substituents on the aniline moiety to
some extent afected the potency of the compounds as well.
For para substitutions, as a representative, the exchange of
Cl (6e) with F (6b) or CF3 (6l) resulted in an about twofold
decrease in activities from 14.4 to 27.2 or 31.6 μg/mL (mean
of three EC50, Table 2), respectively. In comparison with the
precursor structure 6a (R=H), it was found that the introduc-
tion of 4-Cl, 4-OMe, 4-I, 4-Br or 4-Me (6e, 6r, 6j, 6h and
6o, respectively) to the aniline moiety yielded an increase in
the activities in most cases. Indeed, the presence of 4-F (6b)
or 4-CF3 (6l) only resulted in similar or slightly decreased
1 3

Molecular Diversity
Table 2 Antifungal activities of
Compounds
No.
EC50 (95% CIa) (μg/mL)
C. lunata P. grisea
Mean (μg/mL)
2-phenyl-4-aminoquinolines
R
A. alternate
6a
H
4′-F
3′-F
2′-F
4′-Cl
3′-Cl
2′-Cl
4′-Br
24.9 (21.9–28.2) 28.7 (26.6–31.0) 27.0 (23.7–30.6) 26.9
24.0 (23.0–25.0) 32.7 (29.7–36.4) 25.0 (22.4–27.8) 27.2
6b
6c
≥50b
22.1 (19.0–25.5) 21.0 (16.9–24.6)
–
–
6d
≥50b
≥100b ≥50b
6e
13.3 (12.4–14.2) 14.4 (13.0–15.8) 15.6 (14.1–17.2) 14.4
6f
≥50b
34.7 (32.2–37.3) 40.5 (37.9–43.3)
–
–
6g
≥50b
≥50b
41.4 (39.4–43.4)
6h
30.2 (28.1–32.4) 17.4 (15.8–19.1) 24.1 (20.6–28.2) 23.9
15.6 (14.3–16.8) 23.4 (21.4–25.2) ≥50b
30.8 (27.7–33.6) 20.2 (18.0–22.5) 16.9 (15.4–18.3) 22.6
16.0 (14.8–17.2) 31.0 (29.0–33.1) ≥50b
6i
3′-Br
4′-I
3′-I
–
6j
6k
–
6l
4′-CF3
3′-CF3
2′-CF3
4′-Me
3′-Me
2′-Me
4′-OMe
3′-OMe
2′-OMe
3′,5′-diOMe
dimethylamine
39.4 (36.1–42.8) 29.1 (26.0–32.3) 26.2 (23.3–29.1) 31.6
6m
≥100b
≥100b
≥100b
49.8 (46.4–53.6)
–
–
6n
38.8 (36.2–41.5) ≥50b
6o
25.8 (22.7–29.0) 22.7 (19.8–25.7) 22.6 (20.0–25.2) 23.7
6p
≥50b
≥50b
≥50b
–
–
6q
48.7 (44.8–53.0) 44.2 (40.6–48.6) ≥50b
6r
22.0 (20.9–23.2) 20.9 (17.7–24.4) 19.2 (17.8–20.7) 20.7
6s
≥50b
≥50b
≥50b
–
–
–
–
–
6t
≥100b
≥100b
≥100b
≥100b
≥50b
≥100b
≥50b
6u
7
8
≥100b
≥100b
1,2,4-1H-triazole ≥100b
≥100b
≥100b
Azoxystrobin
75.0 (71.8–78.6) 34.5 (31.7–37.6) 16.0 (14.7–17.1) 41.8
a95% CI, Confdence intervals at 95% probability
bEstimated values based on the results shown in Table 1
activities. Furthermore, a disubstitution of 3′,5′-diOMe
on the aniline moiety (6u) gave nearly equivalent inhibi-
tory activities compared with the 3′-OMe monosubstituted
derivative 6s. It was worth noting that the electronic efect
(electron donating or electron withdrawing) of the substitu-
ents on the aniline moiety played a minor role.
control azoxystrobin against part or all of the tested fungi.
Among them, compound 6e showed remarkable antifungal
abilities with EC50 values of 13.3–15.6 μg/mL, which was
of great potential to be developed as new antifungal agent.
SAR analysis showed that the aniline moiety at position 4 of
the quinoline scafold was crucial for the potency of a com-
pound. The compounds bearing substituents at para position
of the aniline ring yielded higher inhibitory activities than
that of ortho- or meta-substituted analogs. Moreover, the
electronic efect of the substituents on the aniline moiety
played a minor role.
To confrm the importance of the aniline moiety at posi-
tion 4 of the quinoline scafold, the aniline residue was sub-
stituted with a dimethylamine or a 1,2,4-1H-triazole moiety
yielding compound 7 and 8, respectively. This modifcation
dramatically decreased the inhibitory potency, whose EC50
values were more than 100 μg/mL in all cases. It was appar-
ent that the aniline moiety at position 4 played a key role
in the inhibitory potency. A graphical summary of the dis-
cussed SAR is given in Fig. 2.
Experimental
All starting materials were obtained from commercial
sources and used without further purifcation. Azoxystrobin
was purchased from Jiangsu Frey Agrochemical Co. Ltd.
(Jiangsu, China). Melting points were measured using X-4
melting point apparatus (Shanghai instrument physical
optics instrument Co. Ltd., China) and were uncorrected. 1H
and 13C NMR spectra were recorded on a Bruker Advance
Conclusion
In summary, a series of 2-phenyl-4-aminoquinolines were
synthesized and evaluated for their antifungal activities
in vitro. Some of them were more potent than the positive
1 3

Molecular Diversity
Fig. 2 Structure–activity relationship of compounds 6a–6u, 7 and 8
400 or 500 instrument using CDCl3 or DMSO-d6 as deuter-
ated solvent. HRMS-ESI spectra were recorded on a SCIEX
X500R QTOF mass spectrometer.
mixture was cooled to room temperature; the solvent
was removed under vacuum. The residue was dissolved
in water and adjusted to pH = 5–6 by addition of diluted
HCl. With acidifcation of the solution, copious precipi-
tate appeared. The precipitate was collected and washed
successively with water and a cold mixture of CH2Cl2 and
EtOAc (1:1, v/v) to give the pure product as a brown solid.
The phytopathogenic fungi, Curvularia lunata (C.
lunata), Pyricularia grisea (P. grisea) and Alternaria alter-
nate (A. alternate), were provided by the Institute of Pesti-
cides, Northwest A&F University, China. These fungi were
cultured on potato dextrose agar (PDA) at 28 °C and main-
tained at 4 °C with periodic subculturing.
1
Yield: 94%; m.p. 247.7–249.5 °C; H NMR (DMSO-d6,
500 MHz) δ: 11.75 (s, 1H), 8.10 (d, J = 8.1 Hz, 1H), 7.84
(d-like, J = 3.7 Hz, 2H), 7.78 (d, J = 8.3 Hz, 1H), 7.68 (t,
J = 8.1 Hz, 1H), 7.59–7.58 (m, 3H), 7.34 (t, J = 7.5 Hz,
1H), 6.34 (s, 1H); 13C NMR (DMSO-d6, 125 MHz) δ:
177.4, 150.5, 141.0, 134.7, 132.3, 130.9, 129.5 (2 × C),
127.9 (2 × C), 125.3, 125.2, 123.8, 119.2, 107.8.
Synthesis of intermediate 3
To a mixture of o-aminoacetophenone 1 (0.1 mol), anhy-
drous CH2Cl2 (100 mL) and triethylamine (0.1 mol), a solu-
tion of benzoyl chloride 2 (0.1 mol) in CH2Cl2 (50 mL) was
added in dropwise under ice bath. The reaction mixture
was stirred for 3 h at room temperature. Then, the mix-
ture was extracted with CH2Cl2 (3×80 mL), and the com-
bined organic layers washed with water (3 × 100 mL) and
then dried with Na2SO4. After removal of the solvent, the
crude product was recrystallized from petroleum ether/ethyl
acetate (10:1, v/v) to aford 3 as a white solid. Yield: 97%;
m.p. 97.0–98.4 °C; 1H NMR (CDCl3, 500 MHz) δ: 8.98 (d,
J=6.6 Hz, 1H), 8.07 (d, J=6.6 Hz, 2H), 7.96–7.93 (m, 1H),
7.63–7.60 (m, 1H), 7.57–7.51 (m, 3H), 7.17–7.13 (m, 1H),
2.71 (s, 3H); 13C NMR (CDCl3, 125 MHz) δ: 203.8, 166.6,
142.0, 136.0, 135.3, 132.6, 132.4, 129.4 (2 × C), 128.0
(2×C), 123.0, 122.5, 121.3, 29.2.
Synthesis of intermediate 5
To a solution of quinolinone 4 (0.08 mol) in 1,4-diox-
ane (50 mL), POCl3 (80 mL) was added. The resulting
mixture was heated to refux for 6 h. After cooling, the
solvent was removed by evaporation and the residue was
poured into cold water. Then, the mixture was neutral-
ized with a cold saturated solution of NaOH and extracted
with CH2Cl2 (3 × 80 mL). After extraction and evapora-
tion of the solvent, the product was recrystallized from
petroleum ether/ethyl acetate (20:1, v/v) to yield 5 as a
1
white solid. Yield: 64%; m.p. 81.8–83.5 °C; H NMR
(CDCl3, 400 MHz) δ: 8.13 (t, J=9.4 Hz, 2H), 8.06 (d-like,
J = 8.4 Hz, 2H), 7.89 (s, 1H), 7.69 (td, J = 7.1, 1.2 Hz,
Synthesis of intermediate 4
1H), 7.54 (td, J = 7.6, 0.5 Hz, 1H), 7.47–7.38 (m, 3H). 13
C
NaOH (0.27 mol) was added to a solution of amide 3
(0.09 mol) in 1,4-dioxane (200 mL). The mixture was
heated to 110 °C for 2 h under stirring. After the reaction
NMR (CDCl3, 100 MHz) δ: 157.3, 149.1, 143.1, 138.6,
130.6, 130.1, 129.8, 128.9 (2 × C), 127.5 (2 × C), 127.2,
125.3, 124.0, 119.1.
1 3

Molecular Diversity
11.44 (s, 1H), 9.09 (d, J=8.5 Hz, 1H), 8.58 (d, J=8.5 Hz,
1H), 8.03 (t, J=7.8 Hz, 1H), 7.91 (d, J=7.7 Hz, 2H), 7.78
(t, J=7.7 Hz, 1H), 7.71 (t, J=7.8 Hz, 1H), 7.64~7.48 (m,
General procedure for the synthesis of 6a–6u
The 4-chloroquinoline 5 (3 mmol) and corresponding
arylamine (5 mmol) were dissolved in dry 1,4-dioxane
(8 mL), and the above mixture was stirred at 110 °C for
several hours until the reaction was complete (as indicated
by TLC analysis). After the reaction mixture was cooled
to room temperature, the resultant precipitate was fltered,
washed with petroleum ether/ethyl acetate (20:1, v/v) to
yield the target compounds 6a–6u.
5H), 7.42 (t, J=7.2 Hz, 1H), 6.59 (d, J=2.1 Hz, 1H). 13
C
NMR (DMSO-d6, 100 MHz) δ: 157.2 (d, J = 249.2 Hz),
155.4, 153.4, 139.5, 134.4, 132.3, 132.2, 130.4 (d,
J=7.8 Hz), 129.6 (2×C), 129.4, 129.0 (2×C), 127.5, 126.2
(d, J=3.1 Hz), 124.9 (d, J=12.1 Hz), 124.4, 121.1, 117.5
(d, J=19.4 Hz), 116.8, 99.5. HR-MS: 315.1277 ([M-Cl]+,
+
C21H16FN2 ; calc. 315.1292).
N‑(4‑Chlorophenyl)‑2‑phenylquinolin‑4‑amine hydro‑
chloride (6e) Yield: 64%; yellow solid; m.p. 272.4–
274.0 °C; 1H NMR (DMSO-d6, 500 MHz) δ: 14.43 (s, 1H),
11.25 (s, 1H), 8.95 (d, J=8.4 Hz, 1H), 8.44 (d, J=8.4 Hz,
1H), 8.08 (t, J=7.7 Hz, 1H), 7.98 (d, J=7.3 Hz, 2H), 7.84
(t, J = 7.7 Hz, 1H), 7.72–7.64 (m, 7H), 7.05 (s, 1H). 13C
NMR (DMSO-d6, 125 MHz) δ: 154.9, 153.5, 139.7, 136.8,
134.5, 132.6, 132.4, 131.7, 130.3 (2 × C), 129.7 (2 × C),
129.1 (2 × C), 127.5 (2 × C), 124.2, 121.2, 117.2, 99.5.
N,2‑Diphenylquinolin‑4‑amine hydrochloride
(6a) Yield: 70%; yellow solid; m.p. 252.4–253.6 °C; H
1
NMR (DMSO-d6, 400 MHz) δ: 14.53 (s, 1H), 11.36 (s,
1H), 9.03 (d, J = 8.3 Hz, 1H), 8.52 (d, J = 8.3 Hz, 1H),
8.04 (t, J = 7.4 Hz, 1H), 7.93 (d, J = 6.7 Hz, 2H), 7.79 (t,
J = 7.4 Hz, 1H), 7.67–7.56 (m, 7H), 7.32 (br s, 1H), 6.95
(s, 1H). 13C NMR (DMSO-d6, 100 MHz) δ: 155.1, 153.2,
139.7, 137.8, 134.4, 132.6, 132.3, 130.4 (2 × C), 129.7
(2 × C), 129.0 (2 × C), 127.8, 127.3, 125.8 (2 × C), 124.4,
+
HR-MS: 331.0976 ([M-Cl]+, C21H16ClN2 ; calc. 331.0997).
+
121.2, 117.1, 99.2. HR-MS: 297.1369 ([M-Cl]+, C21H17N2 ;
calc. 297.1386).
N‑(3‑Chlorophenyl)‑2‑phenylquinolin‑4‑amine hydro‑
chloride (6f) Yield: 48%; light yellow solid; m.p. 141.2–
142.4 °C; 1H NMR (DMSO-d6, 400 MHz) δ: 14.64 (s, 1H),
11.48 (s, 1H), 9.06 (d, J=8.4 Hz, 1H), 8.54 (d, J=8.4 Hz,
1H), 8.04 (t, J=7.6 Hz, 1H), 7.98 (d, J=6.8 Hz, 2H), 7.78
(t, J=7.6 Hz, 1H), 7.73 (t, J=1.8 Hz, 1H), 7.69~7.57 (m,
5H), 7.46 (dd, J=7.9, 0.7 Hz, 1H), 7.06 (s, 1H). 13C NMR
(DMSO-d6, 100 MHz) δ: 154.8, 153.4, 139.7, 139.5, 134.4,
132.5, 132.3, 131.8, 129.6 (2 × C), 129.1 (2 × C), 127.4,
125.5, 124.5, 124.1, 121.2, 117.2, 99.8. HR-MS: 331.0990
N‑(4‑Fluorophenyl)‑2‑phenylquinolin‑4‑amine hydro‑
chloride (6b) Yield: 78%; yellow solid; m.p. 277.2–
279.0 °C; 1H NMR (DMSO-d6, 400 MHz) δ: 14.48 (s, 1H),
11.30 (s, 1H), 8.99 (d, J=8.3 Hz, 1H), 8.48 (d, J=8.3 Hz,
1H), 8.04 (t, J=7.4 Hz, 1H), 7.94 (d, J=6.8 Hz, 2H), 7.78
(t, J=7.4 Hz, 1H), 7.68–7.59 (m, 5H), 7.41 (t, J=8.8 Hz,
2H), 6.90 (s, 1H). 13C NMR (DMSO-d6, 100 MHz) δ: 161.2
(d, J = 244.4 Hz), 155.3, 153.3, 139.7, 134.4, 134.1 (d,
J=2.8 Hz), 132.6, 132.3, 129.7 (2×C), 129.1 (2×C), 128.2
(d, J=8.6 Hz), 127.3, 124.3, 121.2, 117.2 (d, J=22.8 Hz),
+
([M-Cl]+, C21H16ClN2 ; calc. 331.0997).
+
117.0, 99.1. HR-MS: 315.1275 ([M-Cl]+, C21H16FN2 ; calc.
N‑(2‑Chlorophenyl)‑2‑phenylquinolin‑4‑amine hydro‑
chloride (6g) Yield: 55%; gray solid; m.p. 151.8–153.2 °C;
1H NMR (DMSO-d6, 400 MHz) δ: 14.66 (s, 1H), 11.43
(s, 1H), 9.01 (d, J=8.5 Hz, 1H), 8.55 (d, J=8.5 Hz, 1H),
8.09 (t, J = 7.7 Hz, 1H), 7.89 (d, J = 7.0 Hz, 2H), 7.85 (t,
J = 7.8 Hz, 1H), 7.78 (dd, J = 7.7, 1.5 Hz, 1H), 7.72 (dd,
315.1292).
N‑(3‑Fluorophenyl)‑2‑phenylquinolin‑4‑amine hydro‑
chloride (6c) Yield: 53%; yellow solid; m.p. 119.7–
120.3 °C; 1H NMR (DMSO-d6, 400 MHz) δ: 14.63 (s, 1H),
11.43 (s, 1H), 9.05 (d, J=8.4 Hz, 1H), 8.53 (d, J=8.4 Hz,
1H), 8.05 (t, J=7.7 Hz, 1H), 7.99 (d, J=6.8 Hz, 2H), 7.80
(t, J=7.7 Hz, 1H), 7.70 ~7.51 (m, 6H), 7.25 (td, J =12.7,
2.0 Hz, 1H), 7.10 (s, 1H). 13C NMR (DMSO-d6, 100 MHz)
δ: 163.0 (d, J = 244.8 Hz), 154.8, 153.5, 139.8, 139.7 (d,
J=7.0 Hz), 134.4, 132.5, 132.3, 131.9 (d, J=9.3 Hz), 129.6
(2×C), 129.1 (2×C), 127.4, 124.4, 121.5 (d, J=2.4 Hz),
121.2, 117.2, 114.3 (d, J=20.9 Hz), 112.8 (d, J=23.9 Hz),
99.8. HR-MS: 315.1277 ([M-Cl]+, C21H16FN2+; calc.
315.1292).
J=7.6, 1.5 Hz, 1H), 7.68~7.55 (m, 5H), 6.42 (s, 1H). 13
C
NMR (DMSO-d6, 100 MHz) δ: 155.5, 153.4, 139.5, 134.6,
132.4, 132.3, 131.4, 131.3, 130.6, 130.3, 129.7 (2 × C),
129.5, 129.0 (2 × C), 127.7, 124.2, 121.3, 116.6, 99.5.
+
HR-MS: 331.0991 ([M-Cl]+, C21H16ClN2 ; calc. 331.0997).
N‑(4‑Bromophenyl)‑2‑phenylquinolin‑4‑amine hydro‑
chloride (6h) Yield: 75%; light yellow solid; m.p. 187.3–
189.2 °C; 1H NMR (DMSO-d6, 500 MHz) δ: 14.45 (s, 1H),
11.24 (s, 1H), 8.96 (d, J=8.4 Hz, 1H), 8.44 (d, J=8.4 Hz,
1H), 8.08 (t, J=7.6 Hz, 1H), 7.98 (d, J=7.3 Hz, 2H), 7.83
(t, J = 7.6 Hz, 1H), 7.77 (d, J = 8.3 Hz, 2H), 7.71–7.64
(m, 3H), 7.61 (d, J = 8.3 Hz, 2H), 7.07 (s, 1H). 13C NMR
N‑(2‑Fluorophenyl)‑2‑phenylquinolin‑4‑amine hydro‑
chloride (6d) Yield: 87%; light yellow solid; m.p. 141.2–
142.2 °C; 1H NMR (DMSO-d6, 400 MHz) δ: 14.73 (s, 1H),
1 3

Molecular Diversity
(DMSO-d6, 125 MHz) δ: 154.7, 153.5, 139.7, 137.3, 134.4,
133.3 (2 × C), 132.7, 132.3, 129.7 (2 × C), 129.1 (2 × C),
127.7 (2 × C), 127.5, 124.2, 121.3, 120.0, 117.2, 99.5.
2‑Phenyl‑N‑(3‑(trifluoromethyl)phenyl)quino‑
lin‑4‑amine hydrochloride (6m) Yield: 43%; light yellow
solid; m.p. 177.3–178.1 °C; 1H NMR (DMSO-d6, 400 MHz)
δ: 14.70 (s, 1H), 11.60 (s, 1H), 9.09 (d, J = 8.5 Hz, 1H),
8.56 (d, J=8.5 Hz, 1H), 8.08~7.98 (m, 5H), 7.82~7.74 (m,
3H), 7.69~7.60 (m, 3H), 7.12 (s, 1H). 13C NMR (DMSO-d6,
100 MHz) δ: 154.8, 153.5, 139.8, 139.0, 134.4, 132.5, 132.4,
131.5, 130.9 (q, J = 32.2 Hz), 129.6 (2 × C), 129.2, 129.1
(2×C), 127.5, 124.4, 124.3 (q, J=272.5 Hz, –CF3), 123.8
(d, J = 3.2 Hz), 122.3 (d, J = 3.5 Hz), 121.2, 117.4, 99.8.
+
HR-MS: 375.0473 ([M-Cl]+, C21H16BrN2 ; calc. 375.0491).
N‑(3‑Bromophenyl)‑2‑phenylquinolin‑4‑amine
hydrochloride (6i) Yield: 40%; yellow solid; m.p. 222.1–
223.3 °C; 1H NMR (DMSO-d6, 400 MHz) δ: 14.55 (s, 1H),
11.36 (s, 1H), 9.00 (d, J=8.5 Hz, 1H), 8.48 (d, J=8.5 Hz,
1H), 8.07 (t, J=7.8 Hz, 1H), 7.97 (d, J=7.5 Hz, 2H), 7.85
(s, 1H), 7.82 (t, J =7.7 Hz, 1H), 7.70 ~7.61 (m, 5H), 7.54
(t, J = 8.0 Hz, 1H), 7.08 (s, 1H). 13C NMR (DMSO-d6,
100 MHz) δ: 154.8, 153.5, 139.7, 139.6, 134.5, 132.6, 132.4,
132.1, 130.3, 129.7 (2 × C), 129.1 (2 × C), 128.4, 127.5,
124.5, 124.3, 122.7, 121.2, 117.2, 99.8. HR-MS: 375.0487
+
HR-MS: 365.1248 ([M-Cl]+, C22H16F3N2 ; calc. 365.1260).
2‑Phenyl‑N‑(2‑(trifluoromethyl)phenyl)quino‑
lin‑4‑amine hydrochloride (6n) Yield: 28%; white solid;
1
m.p. 204.5–206.3 °C; H NMR (DMSO-d6, 400 MHz)
+
([M-Cl]+, C21H16BrN2 ; calc. 375.0491).
δ: 14.79 (s, 1H), 11.41 (s, 1H), 9.02 (d, J = 8.5 Hz, 1H),
8.63 (d, J = 8.5 Hz, 1H), 8.09 (t, J = 7.8 Hz, 1H), 8.03 (d,
J = 7.8 Hz, 1H), 7.97 (t, J = 7.5 Hz, 1H), 7.87 ~ 7.78 (m,
5H), 7.67~7.56 (m, 3H), 6.33 (s, 1H). 13C NMR (DMSO-d6,
100 MHz) δ: 156.9, 153.3, 139.5, 135.4, 134.5, 132.4, 132.2,
131.6, 130.2, 129.6 (2×C), 129.1 (2×C), 128.9, 128.3 (d,
J=4.8 Hz), 127.8 (q, J=29.9 Hz), 127.7, 124.1, 123.7 (q,
J=274.0 Hz, -CF3), 121.3, 116.6, 99.5. HR-MS: 365.1248
N‑(4‑Iodophenyl)‑2‑phenylquinolin‑4‑amine hydro‑
chloride (6j) Yield: 77%; gray solid; m.p. 271.1–273.0 °C;
1H NMR (DMSO-d6, 400 MHz) δ: 14.31 (s, 1H), 11.10
(s, 1H), 8.87 (d, J=8.5 Hz, 1H), 8.36 (d, J=8.5 Hz, 1H),
8.06 (t, J = 7.7 Hz, 1H), 7.94 (d, J = 8.3 Hz, 2H), 7.91 (d,
J=8.5 Hz, 2H), 7.82 (t, J=7.6 Hz, 1H), 7.70–7.59 (m, 3H),
7.42 (d, J = 8.5 Hz, 2H), 7.06 (s, 1H). 13C NMR (DMSO-
d6, 100 MHz) δ: 154.1, 152.8, 139.1, 138.5 (2×C), 137.2,
133.8, 132.0, 131.8, 129.1 (2 × C), 128.6 (2 × C), 127.1
(2 × C), 126.9, 123.7, 120.6, 116.7, 99.0, 92.2. HR-MS:
+
([M-Cl]+, C22H16F3N2 ; calc. 365.1260).
2‑Phenyl‑N‑(p‑tolyl)quinolin‑4‑amine hydrochloride
1
(6o) Yield: 62%; yellow solid; m.p. 201.5–203.4 °C; H
+
423.0327 ([M-Cl]+, C21H16IN2 ; calc. 423.0353).
NMR (DMSO-d6, 500 MHz) δ: 14.35 (s, 1H), 11.18 (s, 1H),
8.94 (d, J = 8.4 Hz, 1H), 8.44 (d, J = 8.4 Hz, 1H), 8.06 (t,
J=7.7 Hz, 1H), 7.92 (d, J=7.1 Hz, 2H), 7.81 (t, J=7.7 Hz,
1H), 7.70–7.62 (m, 3H), 7.49 (d, J = 8.1 Hz, 2H), 7.40
(d, J = 8.1 Hz, 2H), 6.91 (s, 1H), 2.41 (s, 3H). 13C NMR
(DMSO-d6, 125 MHz) δ: 155.2, 153.2, 139.7, 137.3, 135.0,
134.3, 132.8, 132.3, 130.9 (2 × C), 129.7 (2 × C), 128.9
(2×C), 127.3, 125.7 (2×C), 124.1, 121.2, 116.9, 99.0, 21.2.
N‑(3‑Iodophenyl)‑2‑phenylquinolin‑4‑amine hydro‑
chloride (6k) Yield: 41%; light yellow solid; m.p. 212.4–
214.0 °C; 1H NMR (DMSO-d6, 400 MHz) δ: 14.51 (s, 1H),
11.29 (s, 1H), 8.97 (d, J=8.5 Hz, 1H), 8.47 (d, J=8.5 Hz,
1H), 8.07 (t, J=7.7 Hz, 1H), 7.98 (d, J=6.1 Hz, 2H), 7.96
(s, 1H), 7.83 (d, J=7.6 Hz, 1H), 7.79 (d, J=8.6 Hz, 1H),
7.71~7.63 (m, 4H), 7.38 (t, J =8.0 Hz, 1H), 7.05 (s, 1H).
13C NMR (DMSO-d6, 100 MHz) δ: 154.8, 153.4, 139.7,
139.4, 136.2, 134.4, 134.0, 132.6, 132.4, 132.1, 129.7
(2 × C), 129.1 (2 × C), 127.5, 124.9, 124.2, 121.2, 117.2,
+
HR-MS: 311.1526 ([M-Cl]+, C22H19N2 ; calc. 311.1543).
2‑Phenyl‑N‑(m‑tolyl)quinolin‑4‑amine hydrochloride
1
(6p) Yield: 93%; yellow solid; m.p. 146.0–147.2 °C; H
+
99.7, 95.8. HR-MS: 423.0341 ([M-Cl]+, C21H16IN2 ; calc.
NMR (DMSO-d6, 400 MHz) δ: 14.53 (s, 1H), 11.35 (s,
1H), 9.05 (d, J = 8.5 Hz, 1H), 8.55 (d, J = 8.5 Hz, 1H),
8.01 (t, J = 7.7 Hz, 1H), 7.93 (d, J = 7.2 Hz, 2H), 7.75 (t,
J = 7.7 Hz, 1H), 7.66 ~ 7.58 (m, 3H), 7.47 ~ 7.40 (m, 3H),
7.23 (d, J=7.2 Hz, 1H), 6.91 (s, 1H), 2.39 (s, 3H). 13C NMR
(DMSO-d6, 100 MHz) δ: 155.1, 153.1, 140.0, 139.6, 137.6,
134.2, 132.5, 132.2, 130.1, 129.6 (2 × C), 129.0 (2 × C),
128.4, 127.2, 126.3, 124.4, 122.8, 121.1, 117.0, 99.1, 21.4.
423.0353).
2‑Phenyl‑N‑(4‑(trifluoromethyl)phenyl)quino‑
lin‑4‑amine hydrochloride (6l) Yield: 75%; light yellow
solid; m.p. 294.7–296.3 °C; 1H NMR (DMSO-d6, 400 MHz)
δ: 14.57 (s, 1H), 11.33 (s, 1H), 8.97 (d, J = 8.5 Hz, 1H),
8.44 (d, J = 8.5 Hz, 1H), 8.07 (t, J = 7.7 Hz, 1H), 8.00 (d,
J = 6.8 Hz, 2H), 7.92–7.81 (m, 5H), 7.70–7.62 (m, 3H),
7.27 (s, 1H). 13C NMR (DMSO-d6, 100 MHz) δ: 154.3,
153.8, 142.1, 140.0, 134.5, 132.7, 132.4, 129.7 (2 × C),
129.2 (2×C), 127.6, 127.4 (d, J=4.2 Hz), 125.3, 124.6 (d,
J = 271.8 Hz, -CF3), 124.3, 121.5, 117.6, 100.4. HR-MS:
+
HR-MS: 311.1530 ([M-Cl]+, C22H19N2 ; calc. 311.1543).
2‑Phenyl‑N‑(o‑tolyl)quinolin‑4‑amine hydrochloride
(6q) Yield: 56%; light yellow solid; m.p. 182.0–182.9 °C;
1H NMR (DMSO-d6, 400 MHz) δ: 14.56 (s, 1H), 11.39
(s, 1H), 9.15 (d, J=8.5 Hz, 1H), 8.59 (d, J=8.5 Hz, 1H),
+
365.1240 ([M-Cl]+, C22H16F3N2 ; calc. 365.1260).
1 3

Molecular Diversity
8.03 (t, J = 7.7 Hz, 1H), 7.85 (d, J = 7.0 Hz, 2H), 7.78 (t,
J = 7.7 Hz, 1H), 7.63 ~ 7.54 (m, 3H), 7.50 ~ 7.40 (m, 4H),
6.33 (s, 1H), 2.30 (s, 3H). 13C NMR (DMSO-d6, 100 MHz)
δ: 156.0, 153.2, 139.6, 136.1, 135.8, 134.3, 132.5, 132.3,
132.1, 129.7 (2 × C), 129.0, 128.9 (2 × C), 128.1, 128.1,
127.3, 124.5, 121.2, 116.7, 98.6, 18.0. HR-MS: 311.1535
J=2.1 Hz, 2H), 6.57 (t, J=2.1 Hz, 1H), 3.80 (s, 6H). 13
C
NMR (DMSO-d6, 100 MHz) δ: 161.2 (2×C), 154.5, 152.6,
139.1, 139.0, 133.8, 132.0, 131.7, 129.1 (2 × C), 128.5
(2×C), 126.7, 123.8, 120.6, 116.5, 103.3 (2×C), 99.3, 99.1,
+
55.5 (2 × C). HR-MS: 357.1575 ([M-Cl]+, C23H21N2O2 ;
calc. 357.1598).
+
([M-Cl]+, C22H19N2 ; calc. 311.1543).
General procedure for the synthesis of 7 and 8
N‑(4‑Methoxyphenyl)‑2‑phenylquinolin‑4‑amine
hydrochloride (6r) Yield: 82%; yellow solid; m.p. 174.9–
176.1 °C; 1H NMR (DMSO-d6, 500 MHz) δ: 14.39 (s, 1H),
11.22 (s, 1H), 8.98 (d, J=8.5 Hz, 1H), 8.48 (d, J=8.4 Hz,
1H), 8.04 (t, J=7.7 Hz, 1H), 7.92 (d, J=7.2 Hz, 2H), 7.78
(t, J=7.7 Hz, 1H), 7.68–7.61 (m, 3H), 7.52 (d, J=8.8 Hz,
The 4-chloroquinoline 5 (3 mmol) was dissolved in dry
DMF (10 mL), and the mixture was maintained at 150 °C
for several hours until the reaction was complete. For the
synthesis of compound 8, additional 1,2,4-triazole sodium
(3.6 mmol) was added to the above mixture. After the reac-
tion was fnished, distilled water was added until copious
solid appeared. The solid was collected and washed with
petroleum ether/ethyl acetate (20:1, v/v) to yield the target
compounds.
2H), 7.14 (d, J=8.8 Hz, 2H), 6.83 (s, 1H), 3.85 (s, 3H). 13
C
NMR (DMSO-d6, 125 MHz) δ: 158.7, 155.5, 153.1, 139.6,
134.3, 132.7, 132.2, 130.1, 129.7 (2 × C), 128.9 (2 × C),
127.5 (2 × C), 127.2, 124.1, 121.1, 116.8, 115.5 (2 × C),
98.8, 55.9. HR-MS: 327.1471 ([M-Cl]+, C22H19N2O+; calc.
327.1492).
N,N‑Dimethyl‑2‑phenylquinolin‑4‑amine hydrochlo‑
ride (7) Yield: 64%; yellow solid; m.p. 243.7–245.5 °C;
1H NMR (DMSO-d6, 400 MHz) δ: 14.10 (s, 1H), 8.42 (d,
J=8.6 Hz, 1H), 8.39 (d, J=8.5 Hz, 1H), 8.13 (d, J=7.7 Hz,
2H), 7.97 (t, J =7.7 Hz, 1H), 7.73 ~7.65 (m, 4H), 7.15 (s,
1H), 3.56 (s, 6H). 13C NMR (DMSO-d6, 100 MHz) δ: 159.8,
151.2, 140.8, 133.5, 132.8, 132.2, 129.6 (2 × C), 129.2
(2 × C), 127.5, 125.7, 121.0, 117.5, 102.5, 44.9 (2 × C).
N‑(3‑Methoxyphenyl)‑2‑phenylquinolin‑4‑amine
hydrochloride (6s) Yield: 51%; yellow solid; m.p. 200.9–
202.1 °C; 1H NMR (DMSO-d6, 400 MHz) δ: 14.63 (s, 1H),
11.40 (s, 1H), 9.07 (d, J=8.5 Hz, 1H), 8.58 (d, J=8.5 Hz,
1H), 8.00 (t, J=7.8 Hz, 1H), 7.94 (d, J=6.9 Hz, 2H), 7.73
(t, J=7.7 Hz, 1H), 7.65~7.57 (m, 3H), 7.47 (t, J=8.4 Hz,
1H), 7.21~7.20 (m, 2H), 7.00~6.97 (m, 2H), 3.82 (s, 3H).
13C NMR (DMSO-d6, 100 MHz) δ: 160.8, 155.0, 153.1,
139.7, 139.0, 134.2, 132.5, 132.2, 131.1, 129.6 (2 × C),
129.0 (2 × C), 127.2, 124.4, 121.1, 117.6, 117.1, 113.3,
111.5, 99.5, 55.9. HR-MS: 327.1480 ([M-Cl]+, C22H19N2O+;
calc. 327.1492).
+
HR-MS: 249.1377 ([M-Cl]+, C17H17N2 ; calc. 249.1386).
2‑Phenyl‑4‑(1H‑1,2,4‑triazol‑1‑yl)quinoline (8) Yield:
44%; white solid; m.p. 172.8–173.4 °C; 1H NMR (DMSO-
d6, 400 MHz) δ: 9.39 (s, 1H), 8.53 (s, 1H), 8.42 (s, 1H),
8.39 (d, J = 6.9 Hz, 2H), 8.23 (d, J = 8.4 Hz, 1H), 8.19
(d, J = 8.4 Hz, 1H), 7.89 (td, J= 7.6, 0.9 Hz, 1H), 7.69 (t,
J=7.7 Hz, 1H), 7.61~7.53 (m, 3H). 13C NMR (DMSO-d6,
100 MHz) δ: 157.0, 153.6, 149.5, 146.7, 141.8, 138.2, 131.2,
N‑(2‑Methoxyphenyl)‑2‑phenylquinolin‑4‑amine
hydrochloride (6t) Yield: 54%; yellow solid; m.p. 116.8–
117.5 °C; 1H NMR (DMSO-d6, 400 MHz) δ: 14.56 (s, 1H),
11.14 (s, 1H), 9.01 (d, J=8.4 Hz, 1H), 8.58 (d, J=8.5 Hz,
1H), 8.03 (t, J=7.7 Hz, 1H), 7.88 (d, J=6.8 Hz, 2H), 7.78
(t, J = 7.7 Hz, 1H), 7.64 ~ 7.57 (m, 3H), 7.52 ~ 7.48 (m,
2H), 7.32 (d, J=8.1 Hz, 1H), 7.16 (t, J=7.6 Hz, 1H), 6.41
(s, 1H), 3.85 (s, 3H). 13C NMR (DMSO-d6, 100 MHz) δ:
155.5, 154.7, 152.8, 139.5, 134.2, 132.5, 132.2, 130.0, 129.7
(2 × C), 128.9 (2 × C), 128.6, 127.2, 125.3, 124.2, 121.7,
121.1, 116.6, 113.4, 99.5, 56.3. HR-MS: 327.1482 ([M-Cl]+,
C22H19N2O+; calc. 327.1492).
130.6, 130.0, 129.3 (2 × C), 128.1, 127.9 (2 × C), 123.9,
+
121.2, 114.2. HR-MS: 273.1134 ([M + H]+, C17H13N4
calc. 273.1140).
;
Antifungal assay
Antifungal activities of all the target compounds were evalu-
ated using mycelium growth rate method against three phy-
topathogenic fungi (C. lunata, P. grisea and A. alternate)
as previously reported.[30, 33] The concentration of each
tested compound was 100 or 50 µg/mL in PDA medium.
A 5-mm-diameter mycelium disk was inoculated to the
center of the medium to incubate at 28 °C for 72 h. Each
experiment was performed in triplicate. Meanwhile, 0.5%
DMSO (v/v) in PDA medium and azoxystrobin (100 or
50 µg/mL) were utilized as negative control and positive
control, respectively. After 72 h of treatment, the mycelium
N‑(3,5‑Dimethoxyphenyl)‑2‑phenylquinolin‑4‑amine
hydrochloride (6u) Yield: 68%; yellow solid; m.p. 151.4–
153.0 °C; 1H NMR (DMSO-d6, 400 MHz) δ: 14.36 (s, 1H),
11.08 (s, 1H), 8.88 (d, J=8.5 Hz, 1H), 8.41 (d, J=8.5 Hz,
1H), 8.05 (t, J=7.7 Hz, 1H), 7.91 (d, J=8.5 Hz, 2H), 7.80
(t, J=7.7 Hz, 1H), 7.68–7.63 (m, 3H), 7.05 (s, 1H), 6.77 (d,
1 3

Molecular Diversity
potential anticancer agents. Eur J Med Chem 63:826–832. https
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Inhibition rate(%) = (C − T)∕(C − 5) × 100%
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In the formula, C represents the average diameter of
mycelia in the negative control test, and T represents the
average diameter of mycelia in the compound-treated test.
Serial dilution method was used for determination of
EC50 values according to the same method described above,
ranging from 100 to 6.25 μg/mL. And EC50 values with their
confdence intervals at 95% probability (95% CI) were cal-
culated by Graphpad Prism 7.0.4 (GraphPad Software Inc.,
San Diego, CA, USA).
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Acknowledgements This work was funded by the National Natural
Science Foundation of China (No. 31601670) and the Foundation of
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Compliance with ethical standards
Conflict of interest The authors declare that they have no confict of
interest.
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