Synthesis and anti-neuroinflammatory activity studies of substituted 3,4-dihydroquinoxalin-2-amine derivatives

Article abstract of DOI:10.1016/j.tetlet.2012.03.057

We demonstrate the synthesis of multifunctional 3,4-dihydroquinoxalin-2- amine derivatives 4 through a three-component condensation reactions of a substituted o-phenylenediamines 1 (OPDA), diverse ketones 2 and various isocyanides 3 in the presence of a c

Full text of DOI:10.1016/j.tetlet.2012.03.057

Tetrahedron Letters 53 (2012) 2675–2679
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Tetrahedron Letters
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Synthesis and anti-neuroinflammatory activity studies of substituted
3,4-dihydroquinoxalin-2-amine derivatives
Donthabhakthuni Shobha a,b, Murugulla Adharvana Chari a,c, , Khagga Mukkanti a, Sun Yeou Kim d
⇑
a Dr. MACS Bio-Pharma Pvt. Ltd, Plot-32/A, Western Hills, Kukatpally, Hyderabad 85, AP, India
b Centre for Chemical Sciences & Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad 85, AP, India
c Dept. of Applied Chemistry, Kyung Hee University, 1 Seocheon-dong, Giheung-gu, Yongin-si, Gyeonggi-do 446-701, Global campus, Suwon, Republic of Korea
d Graduate School of East-West Medical Science, Kyung Hee University, Global Campus, #1 Seocheon-dong, Giheung-gu, Yongin, Gyeonggi-do 446-701, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
We demonstrate the synthesis of multifunctional 3,4-dihydroquinoxalin-2-amine derivatives 4 through a
three-component condensation reactions of a substituted o-phenylenediamines 1 (OPDA), diverse
ketones 2 and various isocyanides 3 in the presence of a catalytic amount of p-toluenesulfonic acid (PTSA)
affording excellent yields (82–96%) and 10 mol % of silica gel supported sulfuric acid with good yields
(85–98%) in ethanol at room temperature (2–4 h). We also carried out the anti-neuroinflammatory activ-
ity of 3,4-dihydroquinoxalin-2-amine derivatives and some of the compounds exhibited good activity.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 5 January 2012
Revised 15 March 2012
Accepted 18 March 2012
Available online 24 March 2012
Keywords:
Three component condensation
Various diamines
Diverse ketones
Various isocyanides
3,4-Dihydroquinoxalin-2-amine derivatives
Anti-neuroinflammatory activity
Multi component reactions (MCRs)1 have enormous applica-
tions in the field of drugs and pharmaceuticals and offers significant
benefits like saving energy, time, money and raw materials over
conventional linear step syntheses. MCRs are economically and
environmentally very advantageous and help to avoid the usage
of expensive, toxic and hazardous solvents as against the multi-step
synthesis which involves various steps which produce a consider-
able amount of wastes due to isolation and separation of the prod-
ucts after each step. Among the various multi component reactions,
isocyanide based MCRs (IMCRs)2,3 exhibit a wide range of biological
activities and are extensively used in the pharmaceutical indus-
try.4–6 Among these, quinoxalinones exhibit a wide variety of
biological activity,7–9 including anti-diabetic10 and antiviral
effects.11 Recently, a few reports on the synthesis of various 3,4-
dihydroquinoxaline-2-amines have used p-toluenesulfonic acid
catalyst recycling. We have performed multi component reactions
(MCRs) leading to diverse polysubstituted 3,4-dihydroquinoxalin-
2-amine derivatives starting from simple and readily available pre-
cursors like o-phenylenediamine (OPDA) and chloro substituted
OPDA, diverse ketones and various isocyanides. The reaction is easy
to perform and allows synthesizing various multi functionalized
derivatives. These reaction work-up procedures were simple, chro-
matography-free, and we can isolate products with high purity.
These factors stimulated us to synthesize chloro substituted deriv-
atives, which has to be high in biological activity. Although these
compounds possess interesting biological activities, unfortunately,
to the best of our knowledge, there has been no report available on
the synthesis and anti-neuroinflammatory studies of mono chloro
substituted 3,4-dihydroquinoxalin-2-amine derivatives using pres-
ent catalysts in the open literature so far. Herein, we demonstrate a
simple, convenient and efficient method for the synthesis of
3,4-dihydroquinoxalin-2-amine derivatives with ethanol solvent
using PTSA or silica gel supported sulfuric acid catalyst through
one pot condensation reaction of substituted o-phenylenediamines,
diverse ketones, and various isocyanides. In the present work, 3,4-
dihydroquinoxalin-2-amine derivatives are synthesized and evalu-
ated for anti-neuroinflammatory studies for the first time.
(PTSA),3d Fe(ClO4)3 CAN,13 EDTA,14 AlKIT-515 and Amberlyst.16
12
Unfortunately, many reports3d,12–14 use homogenous catalysts
and are not recyclable. The use of heterogeneous catalysts17–19
has received considerable importance in organic synthesis because
of their ease of handling, enhanced reaction rates, greater selectiv-
ity, simple work-up, and recoverability of catalysts. Among the
various heterogeneous catalysts, particularly, silica gel-supported
sulfuric acid19 has advantages of low cost, ease of preparation and
Initially to optimize the reaction conditions, o-phenylenedi-
amine 1 (0.108 g, 1 mmol), butanone 2 (0.072 g, 1 mmol), and cyclo-
hexyl isocyanide 3 (0.109 g, 1 mmol) were employed for the
synthesis of 3,4-dihydroquinoxalin-2-amine derivative 4a (Table 1,
⇑
Corresponding author.
E-mail address: drmac_s@yahoo.com (M.A. Chari).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.03.057

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D. Shobha et al. / Tetrahedron Letters 53 (2012) 2675–2679
Table 1
Synthesis of 3,4-dihydroquinoxalin-2-amine derivatives via Scheme 1 and inhibitory activities on NO production in LPS-activated microglia
Timea (h)
Yieldb (%)
Inhc (%)
IC50 (
lM)
d
Entry
Diamine (1)
Ketone (2)
Isocyanide (3)
Product (4)
NH2
O
H
N
CH3
CH2-CH3
N
N
C
C
a
3
92 (95)
—
—
H3C
CH2-CH3
NH2
N
N
H
NH2
NH2
O
H
N
b
c
3
3
89 (92)
92 (95)
—
—
—
—
N
N
H
NH2
NH2
O
O
CH3
H
N
N
N
C
C
CH3
CH3
N
H
N
NH2
NH2
H2N
CH3
H
N
d
3
88 (91)
—
—
NH2
N
N
H
NH2
NH2
O
CH3
H
N
N
N
N
C
C
C
e
f
4
2
88 (90)
96 (98)
1.25
36.46
Br
CH3
N
N
H
Br
NH2
NH2
O
CH3
H
N
—
—
CH3
CH3
N
N
H
H3C
NH2
NH2
NH2
O
O
H2N
g
3
3
90 (94)
—
—
—
—
H
N
N
N
H
NH2
NH2
CH3
H
N
N
C
h
90 (94)
CH3
N
NH
NH2
NH2
O
CH3
H
N
N
C
i
3
3
3
90 (93)
88 (91)
86 (87)
—
—
CH3
CH3
N
NH
H3C
H3C
Cl
Cl
NH2
NH2
O
H
N
CH3
CH2-CH3
N
N
C
C
Cl
j
4.32
49.90
40.48
CH2-CH3
N
N
H
NH2
NH2
O
H
N
Cl
k
—
N
N
H

D. Shobha et al. / Tetrahedron Letters 53 (2012) 2675–2679
2677
M)
Table 1 (continued)
Entry Diamine (1)
d
Ketone (2)
Isocyanide (3)
Product (4)
Timea (h)
Yieldb (%)
89 (92)
Inhc (%)
19.08
IC50 (l
Cl
NH2
NH2
O
H
N
CH3
N
N
C
C
Cl
l
3
25.85
CH3
CH3
N
N
H
Cl
NH2
NH2
O
H2N
CH3
H
N
m
3
86 (88)
—
—
Cl
Cl
NH2
N
N
H
NH2
NH2
O
H
N
CH3
Cl
Cl
N
N
C
C
n
o
4
3
82 (85)
90 (91)
19.62
9.69
56.53
69.11
Br
CH3
N
N
H
Br
NH2
NH2
O
CH3
H
N
Cl
CH3
CH3
N
N
H
H3C
Cl
NH2
NH2
NH2
O
H2N
N
C
H
N
p
3
86 (88)
—
—2
Cl
N
N
H
a
b
c
Reaction time for the preparation of 4a–p.
Isolated yield in the synthesis using PTSA (silicagel supported sulfuric acid yields are in brackets).
Values obtained through three experiments and the mean inhibition of NO production relative to the LPS control at 10 lM concentration of compounds.
d
IC50 values for the compounds 4a–p.
entry a) in the presence of a catalytic amount of PTSA (5 mol %,
0.095 g) or 10 mol % of silica gel supported sulfuric acid in ethanol
at room temperature for 3 h. (Scheme 1).
Furthermore, cyclic ketones were then introduced to prepare struc-
turally interesting spirocyclic compounds (Table 1, entry b and k).
Chloro substituted diamines and various substituted aromatic
ketones were used to synthesize multifunctionalized 3,4-dihy-
dro-quinoxalin-2-amine derivatives to evaluate their biological
activity. In addition, benzophenone also underwent a smooth con-
version to the corresponding product with reasonable yields
(Table 1, entry g and p). The detection of these compounds is very
easy, since the compounds were yellow and brown. We obtained
reasonable yield for compound 4k in Table 1, which may be due
to the effect of steric hindrance. Some of the compound (Table 1,
entry f, i and o) yields are more in short time which may be due
to the presence of electron donating methyl groups. The recyclabil-
ity of the silica gel supported sulfuric acid catalyst (Table 1, entry
4a) was also studied and we found that the catalyst showed 92,
87, and 84% of yields in 2nd, 3rd, and 4th cycles, respectively.
The possible mechanism for the formation of product 4 is
shown in Scheme 2. Product 4 is formed by the initial formation
As shown in Table 1, various substituted o-phenylenediamines
1, ketones 2 and isocyanides 3 were used in the presence of
5 mol % PTSA catalyst (or) 10 mol % of silica gel supported sulfuric
acid at room temperature for 2–4 h under ethanol solvent to syn-
thesize the multifunctionalized compounds.24 Several diversified
isocyanides 3 including cyclohexyl and benzyl substituted ones
were used to get products 4 in excellent yields. All synthesized
products (4a–p) were stable and characterized by using IR, 1H
NMR, and MALDI-Mass spectral analysis and also by their elemen-
tal analysis and melting points. However, the reactions are quite
clean and no other side products were observed. Diamines and
mono chloro substituted diamines 1, aliphatic, aromatic and cyclic
ketones 2, and cyclohexyl and benzyl isocyanides 3 gave good
yields (Table 1, entry 4a–p). As shown in Table 1, aliphatic ketones
also reacted well and gave good yield (Table 1, entries a and j).
R2
H
N
R1
NH2
R1
PTSA/ Silica gel supported
sulphuric acid
EtOH, R.T., 2 - 4 h
O
2
R3
+
R4
N C
R2
R3
+
R4
NH2
N
N
H
1
3
4
R4 = Cyclohexyl, Benzyl
R2 = Alkyl
R1= H, Cl
R3 = Alkyl, Phenyl
Scheme 1. Synthesis of 3,4-dihydroquinoxalin-2-amine derivatives.

2678
D. Shobha et al. / Tetrahedron Letters 53 (2012) 2675–2679
R2
R3
PTSA/Silica supported sulfuric acid
R1
R3
H
N
R1
NH2
NH2
O
+
R4
N
C
R2
+
NH2
1
2
A
3
R2
R2
H
N
R2
R3
H
N
R1
H
N
R1
R1
-H
R3
R3
R4
R4
N
N
N
N
H
N
NH2
H
R4
C
B
4
Scheme 2. Proposed mechanism for the synthesis of 3,4-dihydroquinoxalin-2-amine derivatives 4 using Diamines 1, Ketones 2 and Isocyanides 3.
of iminium intermediate A from diamine 1 and ketone 2. Interme-
diate B was produced by the nucleophilic attack of isocyanide 3 to
activate the iminium intermediate A and then by an intramolecular
nucleophilic attack of NH2 group to the activated nitrile moiety to
yield intermediate C. Imine-enamine tautomerization of interme-
diate C leads to the formation of product 4.
Anti-neuroinflammatory activity: In the present study we de-
signed and synthesized sixteen 3,4-dihydroquinoxalin-2-amine
derivatives to identify novel neuroprotective agents. Evaluation20–23
of all 3,4-dihydro-quinoxalin-2-amine derivatives synthesized as
potential anti-neuroinflammatory agents was performed using
BV-2 microglia cells. Among the 3,4-dihydroquinoxalin-2-amine
derivatives tested, 4l and 4n compounds strongly inhibited LPS-
induced nitric oxide (NO) production with an IC50 value of 25.85
for further structure–activity relationship studies. Further studies
are required to elucidate precise mechanisms underlying the
anti-inflammatory activity of these compounds (Fig. 1).
In conclusion, we have synthesized a polysubstituted 3,4-dihy-
droquinoxalin-2-amine derivatives using various aromatic dia-
mines, carbonyl compounds, and diverse isocyanides in the
presence of PTSA and silicagel supported sulfuric acid. This method
is applicable to a wide range of substrates and needs simple work-
up, is chromatography-free, and products were recrystallized. The
synthesis of these particular compounds by use of silicagel sup-
ported sulfuric acid has not been reported so far in the literature
to the best of our knowledge. We have reported a new class of
3,4-dihydroquinoxalin-2-amine derivatives that demonstrate
anti-neuroinflammatory activity in microglia cells. Compounds 4l
and 4n (Fig. 1) have shown the highest NO-inhibitory effect on
BV-2 cells. These compounds also showed inhibitory effects on
NO production through the suppression of iNOS enzyme activity.
These results suggest that these compounds may be of beneficial
therapeutic potential for anti-neuroinflammatory diseases through
the inhibition of microglial activation and are suitable targets for
further structure activity relationship studies. Further studies are
required to elucidate the precise mechanisms underlying the
anti-inflammatory activity of these compounds.
and 56.53 lM in the microglia cells. These compounds significantly
inhibited the enzyme activity of inducible NO synthase (iNOS)
without changes of iNOS protein expression and NO scavenging
activity. This result suggests that some of the compounds showed
the anti-neuroinflammatory effect by suppressing iNOS.
The inhibitory activities of NO production by the 3,4-dihydro
quinoxalin-2-amine derivatives were evaluated using LPS-acti-
vated microglia cells. A murine microglia cell line, BV-2, was stim-
ulated with 100 ng/ml LPS for 24 h in the presence or absence of
samples. The presence of nitrite, a soluble oxidation product of
NO, in the culture media was determined by the Griess reaction.
Cell viability was measured21 using a 3-[4,5-dimethylthiazol-
2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay.
As shown in Table 1, the inhibitory activities of the 3,4-dihydro-
quinoxalin-2-amine derivatives varied according to the structure
of substituents. However, some of these compounds showed good
anti-neuroinflammatory activity, which may be due to the steric,
electronic, and structural effects of the compounds.
Acknowledgment
The author D.S. is thankful to Dr. MACS Bio-Pharma Pvt. Ltd for
financial support.
References and notes
1. For reviews, see: (a) Kappe, C. O. Tetrahedron 1993, 49, 6937; (b) Kappe, C. O.
´
Multicomponent Reactions. In Multicomponent Reactions; Zhu, J., Bienayme, H.,
Eds.; Wiley-VCH: Weinheim, Germany, 2005; p 95.
These compounds (Fig. 1) strongly inhibited LPS-induced nitric
oxide (NO) production with IC50 value of 25.85 and 56.53 lM in the
2. For reviews on isocyanides based MCRs, see: (a) Dömling, A.; Ugi, I. Angew.
Chem., Int. Ed. 2000, 39, 3168; (b) Dömling, A. Chem. Rev. 2006, 106, 17; (c) Nair,
V.; Rajesh, C.; Vinod, A. U.; Bindu, S.; Sreekanth, A. R.; Mathen, J. S.; Balagopal, L.
Acc. Chem. Res. 2003, 36, 899.
3. For some recently reported examples with isocyanide, see: (a) Silva, R. A. D.;
Santra, S.; Andreana, P. R. Org. Lett. 2008, 10, 4541; (b) Fujiwara, S.-I.; Asanuma,
Y.; Shin-Ike, T.; Kambe, N. J. Org. Chem. 2007, 72, 8087; (c) Shaabani, A.;
Rezayan, A. H.; Ghasemi, S.; Sarvary, A. Tetrahedron Lett. 2009, 50, 1456; (d)
Shaabani, A.; Maleki, A.; Mofakham, H.; Khavasi, H. R. J. Comb. Chem. 2008, 10,
323.
4. (a) Shaabani, A.; Maleki, A.; Moghimi-Rad, J. J. Org. Chem. 2007, 72, 6309; (b)
Shaabani, A.; Soleimani, E.; Maleki, A. Tetrahedron Lett. 2006, 47, 3031; (c)
Shaabani, A.; Teimouri, M. B.; Arab Ameri, S. Tetrahedron Lett. 2004, 45, 8409.
5. Porter, A. E. A. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C.
W., Eds.; Pergamon Press: NewYork, 1984; Vol.3, p 191.
6. Cheeseman, G. W. H.; Cookson, R. F. In The Chemistry of Heterocyclic Compounds;
Weissberger, A., Taylor, E. C., Eds.; Wiley: New York, 1979; p 1.
7. Jie, J. L.; Carson, K. G.; Trivedi, B. K.; Yue, W. S.; Ye, Q.; Glynn, R. A.; Miller, S. R.;
Connor, D. T.; Roth, B. D.; Luly, J. R.; Low, J. E.; Heilig, D. J.; Yang, W.; Qin, S.;
Hunt, S. Bioorg. Med. Chem. 2003, 11, 3777.
microglial cells. Also, these compounds (Fig. 1) significantly inhib-
ited the enzyme activity of inducible NO synthase (iNOS) without
changes of iNOS protein expression and NO scavenging activity.
This result suggests these compounds 4l and 4n (Fig. 1) showed
the anti-neuroinflammatory effects by suppressing iNOS. These
results indicate that compounds 4l and 4n (Fig. 1) may be of ben-
eficial therapeutic potential for neuroinflammatory diseases
through inhibition of microglial activation and are suitable leads
H
N
H
N
CH3
CH3
Cl
Cl
Br
N
N
N
N
H
H
4l
4n
8. Randle, J. C.; Guet, T.; Bobichon, C.; Moreau, C.; Curutchet, P.; Lambolez, B.;
Carvalho, L. P. D.; Cordi, A.; Lepagnol, J. M. Mol. Pharm. 1992, 41, 337.
9. Yan, L.; Liu, F. W.; Dai, G. F.; Liu, H. M. Bioorg. Med. Chem. Lett. 2007, 17, 609.
Figure 1. Structures of 4l and 4n compounds.

D. Shobha et al. / Tetrahedron Letters 53 (2012) 2675–2679
2679
10. Gupta, D.; Ghosh, N. N.; Chandra, R. Bioorg. Med. Chem. Lett. 2005, 15, 1019.
11. Rosner, M.; Billhardt-Troughton, U. M.; Kirsh, R.; Kleim, J. P.; Meichsner, C.;
Riess, G.; Winkler, I. U.S. Patent, 5723461, 1998.
12. Heravi, M. M.; Baghernejad, B.; Oskooie, H. A. Tetrahedron Lett. 2009, 50, 767.
13. Li, Jian; Liu, Yuejin; Li, Chunju; Jia, Xueshun Tetrahedron Lett. 2009, 50, 6502.
14. Srinivasa Rao, K.; Yong Rok Lee Tetrahedron 2010, 66, 8938.
15. Shobha, D.; Adharvana Chari, M.; Sang, L.-C.; Salem, S. A.; Mukkanti, K.; Vinu, A.
Synlett 2011, 1923.
24. Experimental: All chemicals and solvents were obtained from Aldrich and used
without further purification. Column chromatographic separations were
carried out on silica gel 100–200 mesh size. The 1H NMR spectra of samples
were recorded on a JEOL 300-MHz NMR spectrometer using TMS as an internal
standard in DMSO-d6. Mass spectra were recorded on a MALDI-MS. FT-IR
spectra of all the final products were recorded on
a Perkin–Elmer 100
instrument by averaging 50 scans with a resolution of 2 cmÀ1 measuring in
absorbance mode by using the KBr self-supported pellet technique. The
melting points of the products were determined by using melting point
apparatus. The elemental analysis was performed by using CHN analyser (The
Perkin–Elmer 2400 Series) and were matching with the reported data.16
Preparation of the catalyst: The catalyst was prepared by mixing silica gel (10 g,
200–400 mesh) in dry diethyl ether (50 mL), with sulfuric acid (3 mL). The
resulting mixture was stirred for 30 min to absorb sulfuric acid on the surface
of silica gel. After the removal of solvent in a rotary evaporator, the solid
powder was dried at 120 °C for 2–3 h under reduced pressure.
16. Adharvana Chari, M. Tetrahedron Lett. 2011, 52, 6108.
17. Breton, G. W. J. Org. Chem. 1997, 62, 8952.
18. Chari, M. A.; Syamasundar, K. Catal. Commun. 2005, 6, 67.
19. Roy, B.; Mukopadhya, B. Tetrahedron Lett. 2007, 48, 3783.
20. For the assay the iNOS enzyme activity in intact cells, BV-2 cells were plated in
100 mm tissue culture dishes (4 Â 106 cells) and incubated with LPS (100 ng/
ml) for 12 h. Then, the cells were washed twice with PBS, and cells were
harvested and plated in a 96-well plate (2 Â 105 cells/well), and incubated in
the presence or absence of different concentrations of sample compound for a
further 12 h. The amount of NO in the supernatant was detected by Griess
reaction.
Typical procedure for the synthesis of 3,4-dihydroquinoxalin-2-amine derivatives:
To a solution of diamine 1 (1 mmol), ketone 2 (1 mmol), and isocyanide 3
(1 mmol) in 3 mL of ethanol was added PTSA (0.095 g, 5 mol %) or silica gel
supported sulfuric acid (10 mol %) as catalyst. The resulting mixture was
stirred for 2–4 h at room temperature. After completion of the reaction, as
indicated by TLC (ethyl acetate/n-hexane 2/1), the product was precipitated by
addition of 10 mL of cold water. The precipitate was filtered off and washed
with 5% sodium hydroxide solution and then with water. The residue was
crystallized from ethanol to give 4a–p as crystals. All products were
characterized by spectral (IR, NMR, and Mass) data and also by the melting
points of the samples and compared with the reported literature.16 The
spectral data for selected compound are given below.
21. Western blot was performed to analyze iNOS expression. BV-2 cells were
seeded in a 6-well plate and exposed to LPS (100 ng/ml) in the presence or
absence of sample compound for 6 h. The protein sample (40 lg for each) from
the BV-2 cell extract was separated by 8% SDS–PAGE and transferred to a
nitrocellulose membrane (Amersham Pharmacia Biotech, Buckinghamshire,
UK). The membrane was blocked with 5% skim milk and incubated with
primary antibodies (rabbit anti-iNOS; Transduction Laboratories, San Diego,
CA, USA) and secondary antibodies (goat anti-rabbit IgG; Amersham Pharmacia
Biotech). The blots were developed using ECL Western Blotting Detection
Reagents (Amersham Pharmacia Biotech).
N-cyclohexyl-3-ethyl-3-methyl-3,4-dihydroquinoxalin-2-amine (4a): White solid,
22. Sodium nitroprusside (SNP) was dissolved in phosphate buffered saline (PBS)
mp 217–219 °C (lit. 218–220 °C)16; IR (KBr)
m
max: 3293, 3150, 2935, 1643, 1508,
at 100
l
M. This SNP solution (50
ll) was mixed with 950
ll PBS containing
1178, 750, 681 cmÀ1 1H NMR (DMSO-d6): d 0.88(3H, t, CH3of CH2CH3), 1.22–
;
various concentrations of sample compound (1, 5 and 20
l
M). These mixtures
1.46 (2H, q, CH2of CH2CH3), 1.49 (3H, s, CH3), 1.11–2.34 (10H, m, 5CH2 of
cyclohexyl), 3.91-4.05 (1H, m, CH–NH), 6.30–6.41 (1H, br s, NH), 6.70–6.74
(1H, br s, NH), 6.78–7.65 (4H, m, Ar-H) ppm; MALDI-MS: m/z [M+] = 271; Anal.
Calcd for C17H25N3: C, 75.23; H, 9.28; N, 15.48. Found: C, 75.20; H, 9.24; N,
15.45.
were incubated at 25 °C for 2.5 h, and nitrite formed through the combination
of oxygen and NO released from the SNP, as measured by the Griess reaction.
23. Ha, S. K.; Shobha, D.; Moon, E.; Adharvana Chari, M.; Mukkanti, K.; Kim, S. H.;
Ahn, K. H.; Kim, S. Y. Bioorg. Med. Chem. Lett. 2010, 20, 3969.