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S. K. Sivan et al. / Bioorg. Med. Chem. 21 (2013) 4591–4599
Table 3
Aminocarboxylic acids, amine hydrochlorides used for preparation of substituted urea/thiourea and obtained yields of disubstituted urea/thiourea
Compd
SU1
Aminocarboxylic acid
Amine hydrochloride
Yielda (%)
70
N
CH2NH2
2HCL
NH2
.
HOOCCH2NH2
N
H
N
NH2
NH2
HOOC
HOOC
2HCl
2HCl
.
.
SU3
SU4
SU7
85
76
80
N
H
N
NH2
N
H
N
CH2NH2
2HCL
NH2
.
HOOCCH2NH2
N
H
HOOCH2C
NH2
NH2
2HCl
2HCl
.
.
NH
SU9
60
50
N
N
HOOCH2C
NH2
NH
SU10
a
Yields refer to isolated and chromatographically pure products.
Table 4
d 7.74–7.77 (dd, 4H, J1 = J2 = 2.8 Hz), d 10.62 (s, 2H). IR (KBr) band
at 3298, 1629 cmꢀ1 corresponding to NH and C@O stretching of
amide group. LC–MS: m/z (%) = 445 (M+1, 100).
HIV-1 gp120–CD4 binding inhibition (IC50 values) for synthesized substituted urea
and thiourea
S. No.
Compound
IC50
lM
SD
4.3.3. N,N0-Bis[4-(1H-benzimidazol-2-yl)phenyl]thiourea (SU4)
1H NMR (DMSO-d6, 400 MHz) d 7.09–7.15 (complex peak), d
12.50 (s, 2H); 13C NMR (DMSO-d6, 125 MHz) d = 109.42, 121.93,
132.07, 167.70 IR (KBr) band at 3153 and 1514 cmꢀ1 correspond-
ing to NH and C@S stretching of thiocarbamide group. LC–MS: m/
z (%) = 461 (M+1, 100).
1
2
3
4
5
6
SU1
SU3
SU4
SU7
SU9
SU10
0.247 0.048
0.188 0.036
0.126 0.12
0.013 0.1
0.197 0.0032
0.149 0.0073
4.3.4. N,N0-Bis(1H-benzimidazol-2-ylmethyl)thiourea (SU7)
1H NMR (DMSO-d6, 400 MHz) d 5.51–5.52 (d, 4H, J = 4.8 Hz), d
8.27–8.30 (t, 2H, J1 = 6 Hz, J2 = 5.2 Hz), d 8.46–8.51 (m, 4H), d
8.58–8.60 (d, 4H, J = 8.4 Hz). IR (KBr) band at 3319 cmꢀ1 Corre-
sponding to NH stretching and 1531 cmꢀ1 corresponding to C@S
stretching, LC–MS: m/z (%) = 337 (M+1, 100), HRMS (ESI), m/z calcd
mixture was made by adding few drops of water. Then the vessel
was placed in synthetic microwave oven (Catalyst Cata 2R model)
at 360 W power (100–150 °C) until the mixture was dry. Product
was washed with water to remove any unreacted urea or amine
hydrochloride. Solid was recrystallised from 1:1 methanol–water
purified by column chromatography. Structures were confirmed
by 1H NMR, 13C NMR, IR, LC–MS and HRMS. 1H NMR spectra were
recorded in DMSO-d6 on Bruker (Bio-spin) Ultrashield Arance-III
Nano Bay 400 MHz NMR spectrometer and 13C NMR spectra were
recorded in DMSO-d6 on Avance 500 (125 MHz) spectrometer
using SiMe4 as internal standard. IR spectra were obtained on Ten-
sor-27 (Bruker-optics) FTIR spectrophotometer using KBr disc. LC–
MS were obtained on SHIMADZU 2010A. HRMS were obtained on
Thermo Scientific LTQ Orbitrap.
for
C17H16N6S (M+55(Na–CH3OH adduct)) 391.1622, found
391.1657.
4.3.5. N,N0-Bis[4-(1H-benzimidazol-2-ylmethyl)phenyl]urea
(SU9)
1H NMR (DMSO-d6, 400 MHz) d 4.10 (s, 4H), d 7.12–7.13 (d, 4H,
J = 3.2 Hz), d 7.22–7.24 (d, 4H, J = 8 Hz), d 7.37–7.39 (d, 4H,
J = 7.6 Hz), d 7.46–7.47 (d, 4H, J = 3.2 Hz), d 8.64 (s, 2H). 13C NMR
(DMSO-d6, 125 MHz) d = 33.55, 117.66, 120.84, 128.52, 130,
137.66, 151.88, 153.18. IR (KBr) band at 3601 and 1646 cmꢀ1
corresponding to NH and C@O stretching of amide group. LC–MS:
m/z (%) = 473 (M+1, 100), HRMS (ESI), m/z calcd for C29H24N6O
(MH+) 473.2092, found 473.2071.
4.3.1. N,N0-Bis(1H-benzimidazol-2-ylmethyl)urea (SU1)
1H NMR (DMSO-d6, 400 MHz) d 4.59–4.61 (d, 4H, J = 4.4 Hz), d
7.25 (s, 2H), d 7.33–7.34 (d, 4H), d 7.64–7.65 (d, 4H). IR (KBr) band
at 3361 and 1646 cmꢀ1 corresponding to NH and C@O stretching of
amide group.
4.3.6. N,N0-Bis[4-(1H-benzimidazol-2-ylmethyl)phenyl]thiourea
(SU10)
1H NMR (DMSO-d6, 400 MHz) d 4.38 (s, 4H), d 7.35–7.37 (d, 4H,
J = 8 Hz), d 7.38–7.41 (q, 4H, J = 4 Hz), d 7.52–7.54 (d, 4H, J = 8 Hz), d
7.66–7.69 (q, 4H, J = 4 Hz), d 10.19 (s, 2H). 13C NMR (DMSO-d6,
4.3.2. N,N0-Bis[4-(1H-benzimidazol-2-yl)phenyl]urea (SU3)
1H NMR (DMSO-d6, 400 MHz) d 6.60–6.61 (d, 4H, J = 2.4 Hz), d
7.45–7.49 (q, 4H, J1 = J2 = 6 Hz), d 7. 69–7.72 (q, 4H, J1 = J2 = 6 Hz),