Synthesis of the identical linker mode twin-drug type C2-symmetrical molecules

Article abstract of DOI:10.3987/COM-11-12218

In connection with our studies on antibacterial active compounds against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia coli) strains, some molecular modifications were attempted. In this study, molecular transformations of aminoguan

Full text of DOI:10.3987/COM-11-12218

HETEROCYCLES, Vol. 83, No. 8, 2011
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HETEROCYCLES, Vol. 83, No. 8, 2011, pp. 1843 - 1851. © The Japan Institute of Heterocyclic Chemistry
Received, 26th March, 2011, Accepted, 12th May, 2011, Published online, 23rd May, 2011
DOI: 10.3987/COM-11-12218
SYNTHESIS OF THE IDENTICAL LINKER MODE TWIN-DRUG TYPE
C2-SYMMETRICAL MOLECULES
Fumiko Fujisaki, Haruka Usami, Saya Nakashima, Shiomi Iwashita, Yurie
Kurose, Nobuhiro Kashige, Fumio Miake, and Kunihiro Sumoto
Faculty of Pharmaceutical Science, Fukuoka University, Nanakuma, Jonan-ku,
Fukuoka 814-0180, Japan
kunihiro@adm.fukuoka-u.ac.jp
Abstract – In connection with our studies on antibacterial active compounds
against gram-positive (Staphylococcus aureus) and gram-negative (Escherichia
coli) strains, some molecular modifications were attempted. In this study,
molecular transformations of aminoguanidines and related amines to the
represented C2-symmetrical molecules (Aa–b, Ba–b, and Ca–b) were
investigated. In addition, some C3-symmetrical compounds (Da–b) were also
prepared.
INTRODUCTION
With reference to work on new antibacterial compounds, extensive efforts have been made to find new
promising candidates. Many reports on molecular recognition properties of symmetrical macromolecules
have appeared,1 and it is well known that many receptors or membrane proteins in the native state often
have a high order of symmetrical interface. In the infection process by bacteria or virus,
microorganisms usually use sugar-binding proteins such as lectins.2 We have been interested in
compounds that interfere with such a recognition process in order to find new leads for antibacterial
agents.3 Since molecular recognition via complexes of C2- or C3-symmetry (2-fold or 3-fold symmetrical
geometry) is a common feature of several important receptors,4 we have designed twin-drug type
symmetrical molecules in connection with our studies on antibacterial compounds.5 In this article,
syntheses of target designed C2- or C3-symmetrical molecules in the search for biologically active leads
are described.

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DESIGN OF TARGET SYMMETRICAL MOLECULE
In terms of molecular symmetry, small symmetrical molecules frequently appear in various synthetic
twin-drug type molecules5 and biologically active compounds. Biologically active C2-symmetrical
molecules are usually constructed on a symmetrical alkyl linker or another symmetrical aromatic
template.5,6 For linker mode twin-drug symmetrical molecules, the nature of a linker plays an important
role in binding to the receptor site for biological activity.5,6 It was thought worthwhile to undertake a
synthetic molecular modification study with the aim of obtaining new canditates with antibacterial
activity. From this point of view, molecular modification of aminoguanidines seemed to be interesting
because some aminoguanidine derivatives are known to interfere with the cross-linking of sugar chains.7
Furthermore, a number of bacteria utilize heparan sulfate proteoglycans such as syndecans as attachment
factors for host epithelia for coursing infections in many body sites. Heparan sulfate sugar chains have a
repeated sulfated structure of sugar units.8 These facts encouraged us to design C2-symmetrical structures
having two guanidine groups in the target molecules, because a guanidine functionality (a guanidinium
ion structure in physiological conditions) is expected to interfere with anionic sulfate moieties of heparan
sulfate sugar chains by charge-charge (ionic) interactions.5 We therefore carried out synthetic
investigation of new C2-symmetrical derivatives (Aa, and Ab) (Figure 1). Molecular modification of the
represented C2-symmetrical molecules (A) can be considered to be an identical twin-drug type approach
utilizing a biphenyl scaffold as a linker.
H
H
H
O
O
H2N
N
N
N
NH
R
HN
R
R =
N
NH
b
a
Aa: R = a
Ab: R = b
H
H
H
H
N
R
N
R
R
N
R
N
N
O
O
O
O
Ca: R = a
Cb: R = b
Ba: R = a
Bb: R = b
Figure 1

HETEROCYCLES, Vol. 83, No. 8, 2011
1845
We also designed C2-symmetrical molecules represented as structure B or C (Figure 1). In addition, we
prepared C3-symmetrical cis-1,3,5-trisubstituted molecules Da and Db (Figure 2) from the reaction of
1,3,5-cis-cyclohexanetricarbonyl chloride9 and corresponding aminoguanidines for bioassay and
comparison of antibacterial activity with that of C2-symmetrical target molecules. These modifications to
C3-symmetrical molecules can also be considered to be an identical triplet-drug type approach in the
search for bioactive leads.
H
O
N R
R
HN
H
H
H
H2N
O
N
N
N
R =
NH
O
N
NH
R
b
a
Da: R = a
Db: R = b
Figure 2
CHEMISTRY AND RESULTS
Synthesis of identical linker mode twin-drug type C2-symmetrical molecules (A, B, and C) could be
achieved by condensation reaction of the corresponding dicarbonyl chloride as templates and
aminoguanidines or corresponding amines. The C2-symmetrical structures of the synthesized compounds
were easily confirmed by 13C-NMR spectroscopic analysis. All of the twin-drug type compounds showed
magnetically equivalent spectroscopic signal patterns (appearance of signals assignable to half of the
symmetrical molecules), indicating a C2-symmetrical molecular feature in solution (see Experimental).
Symmetrical target compound (Ba) could be obtained from the reaction of isophthaloyl chloride with
aminoguanidine.
NH2
N
CONHNHC(NH)NH2
N
NH
CONHNHC(NH)NH2
•2HCl
•2HCl
N
•2HCl
H
N
N
CONHNHC(NH)NH2
HN
NH2
NH2
N
N
Bd
Ba
Bc
Figure 3

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TLC analysis of the reaction products of isophthaloyl chloride with aminoguanidine indicated the
formation of three types of derivatives (Figure 3). Compound Ba was easily dehydrated to give cyclized
heterocyclic compounds (Bc and Bd), and the ratio of the three products was dependent on the reaction
conditions. At an elevated reaction temperature, a condensed target derivative (Ba) further proceeded the
intramolecular dehydration reaction of both acyl aminoguanidines in the molecule, and compound Bd
was obtained as a sole product. At a lower reaction temperature, a monodehydrated unsymmetrical
product (Bc) could be isolated (see Experimental). By NMR spectroscopic analysis of signal patterns,
compound Bd also showed a C2-symmetrical molecular feature in solution (see Experimental).
C3-symmetrical compounds (Da and Db) were also prepared from the reaction of
1,3,5-cis-cyclohexanetricarbonyl chloride with corresponding amines. The C3-synmetrical structures of
the products were easily confirmed by 13C-NMR spectroscopic analysis (see Experimental data).
A bioassay for antibacterial activity [determination of the minimum concentrations (MICs) of the
compounds] was carried out by authentic methods according to the Japanese Society of Chemotherapy.
Most of the synthesized C2- or C3-symmetrical molecules showed no remarkable antibacterial activity
against either Escherichia coli (gram-negative) or Staphylococcus aureus (gram-positive). However, two
compounds (Aa and Ab) that used biphenyl as a linker showed significant antibacterial activity (MIC =
0.330 and 0.225 µM/mL, respectively) against E. coli but did not show remarkable antibacterial activity
against S. aureus strain.
Further synthetic applications on the basis of the above chemical and biological information for related
symmetrical derivatives, particularly in the search for biological active lead compounds, are under
investigation.
EXPERIMENTAL
Melting points are uncorrected. IR spectra were measured by a Shimadzu FT/IR-8100 spectrometer. The
1H- and 13C-NMR spectra were obtained by a JEOL JNM A-500 at 35 °C. The chemical shifts were
expressed in  ppm downfield from an internal tetramethylsilane (TMS) signal. The signal assignments
1
1
1
were confirmed by H – H two-dimensional (2D) correlation spectroscopy (COSY), H – 13C
1
heteronuclear multiple quantum coherence (HMQC), and H – 13C heteronuclear multiple-bond
connectivity (HMBC) spectra. High FAB-MS spectra were obtained by a JEOL JMS-HX110 mass
spectrometer.
Assays for Antibacterial Activity
We used S. aureus ATCC6538P and E. coli NBRC14237 (NIHJ) (gram-positive and gram-negative
bacteria, respectively) as target organisms. Synthesized compounds (A, B, C, and D) were dissolved in
dimethyl sulfoxide (DMSO) to a concentration of 1.280 g/mL. The minimum inhibitory concentration

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(MIC) of a standard strain was measured by the authentic microdilution method to monitor the bacterial
growth turbidity in Muller-Hinton broth according to the Japanese Society of Chemotherapy.10,11
2,2'-(4, 4’-Biphenyl-1,1’-dicarbonyl)bis(hydrazinecarboximidamide) Dihydrochloride (Aa)
A mixture of biphenyl-4,4'-dicarbonyl dichloride (0.50 g, 1.79 mmol) and aminoguanidine hydrochloride
(0.79 g, 7.14 mmol) in a round-bottomed flask was heated slowly up to 200 °C in an oil bath and kept for
10 min. After cooling, the mixture was triturated with water. Insoluble material Aa (0.53 g, 69.3%) was
collected by filtration. Mp >200 °C (dec). IR (KBr) cm-1: 3372, 3293, 3211, 3139, 1660, 1626, 1597.
FAB-MS (positive) m/z: 355 (M+H)+. 1H-NMR (DMSO-d6) : 7.4–8.2 (8H, br, C=(N+H2)NH2), 7.92 (4H,
d, J = 8.5 Hz, Ar H-3, H-5, H-3’, H-5’), 8.07 (4H, d, J = 8.5 Hz, Ar H-2, H-6, H-2’, H-6’), 9.75 (2H, br,
13
CONHNH), 10.75 (2H, br, CONHNH), C-NMR (DMSO-d6) : 126.7 (Ar C-3, C-5, C-3’, C-5’), 128.6
(Ar C-2, C-6, C-2’, C-6’), 131.2 (Ar C-1, C-1’), 142.3 (Ar C-4, C-4’), 158.8 (NHC(=NH)NH2), 166.0
(CO). Anal. Calcd for C16H18N8O2 • 2HCl: C, 44.97; H, 4.72; N, 26.22. Found: C, 44.70; H, 4.77; N,
26.50.
N'4,N'4'-Bis(4,5-dihydro-1H-imidazol-2-yl)biphenyl-4,4'-dicarbohydrazide Dihydribromide (Ab)
A mixture of biphenyl-4,4'-dicarbonyl dichloride (0.80 g, 2.86 mmol) and 2-hydrazinoimidazoline
hydrobromide (1.14 g, 6.30 mmol) in a round-bottomed flask was heated slowly up to 190 °C in an oil
bath and kept for 40 min. After cooling, the precipitated material was recrystallized from water to give
Ab dihydrobromide (0.88 g, 54.0%). The mother liquor was made alkaline with K2CO3 and the
precipitated material was filtered to give an Ab free base. To a solution of this free base in MeOH (10
mL) was added a solution of 10% hydrochloride in MeOH (4 mL). Concentration of the solvent gave Ab
hydrochloride (0.48 g, 35.0%, mp >230 °C). Total yield was 89.0%. The following data was shown as
dihydrobromide. Mp >230 °C. IR (KBr) cm-1: 3181, 1683, 1652. FAB-MS (positive) m/z: 407 (M+H)+.
1H-NMR (DMSO-d6) : 3.70 (8H, s, imidazole H-4, H-5), 7.94 (4H, d, J = 8.5 Hz, Ar H-3, H-5, H-3’,
H-5’), 8.06 (4H, d, J = 8.5 Hz, Ar H-2, H-6, H-2’, H-6’), 8.2–9.2 (4H, br, imidazole -NH-C=N+H-), 10.40
(2H, br, CONHNH), 10.92 (2H, br, CONHNH), 13C-NMR (DMSO-d6) : 42.8 (imidazole C-4, C-5),
126.8 (Ar C-3, C-5, C-3’, C-5’), 128.6 (Ar C-2, C-6, C-2’, C-6’), 131.0 (Ar C-1, C-1’), 142.4 (Ar C-4,
C-4’), 160.9 (imidazole C-2), 166.0 (CO). Anal. Calcd for C20H22N8O2 • 2HBr: C, 42.27; H, 4.26; N,
19.72. Found: C, 42.35; H, 4.22; N, 19.66.
Reaction of Isophthaloyl Dichloride with Aminoguanidine Hydrochloride:
Formation of (Ba) and (Bc)
A mixture of isophthaloyl chloride (0.50 g, 2.46 mmol) and aminoguanidine hydrochloride (0.66 g, 5.97
mmol) in a round-bottomed flask was heated slowly up to 177 °C in an oil bath and kept for 10 min. After
cooling, EtOH (5 mL) was added to the reaction mixture and insoluble material Ba (0.44 g, 50.9%) was

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collected by filtration. The filtrate was concentrated in vacuo and the residue was recrystallized from
EtOH to give Bc (0.10 g, 12.2%).
2,2'-(1,3-Phenylenedicarbonyl)bis(hydrazinecarboximidamide) Dihydrochloride (Ba)
1
Mp 233 °C (dec). IR (KBr) cm-1: 1658. FAB-MS (positive) m/z: 279 (M+H)+. H-NMR (DMSO-d6) :
7.64–7.67 (1H, m, Ar H-5), 7.7–8.0 {8H, br, C=(N+H2)NH2}, 8.15–8.16 (2H, m, Ar H-4, H-6), 8.61 (1H, s,
13
Ar H-2), 9.81 (2H, s, CONHNH), 10.87 (2H, br, CONHNH), C-NMR (DMSO-d6) : 127.9 (Ar C-2),
128.3 (Ar C-5), 131.3 (Ar C-4, C-6), 131.9 (Ar C-1, C-3), 158.8 {NHC(=NH)NH}, 165.9 (CO). Anal.
Calcd for C10H14N8O2 • 2HCl • H2O: C, 32.53; H, 4.91; N, 30.35. Found: C, 32.50; H, 4.84; N, 30.36.
2-(3-(5-Amino-4H-1,2,4-triazol-3-yl)phenylcarbonyl)hydrazinecarboximidamide Dihydrochloride
(Bc)
1
Mp >240 °C (EtOH). IR (KBr) cm-1: 1688, 1670, 1651. FAB-MS (positive) m/z: 261 (M+H)+. H-NMR
(DMSO-d6) : 7.2–8.2 [8H, m, {C=(N+H2)NH2} + {triazole –NH + -N+H3}], 7.67 (1H, t, J = 7.9 Hz, Ar
H-5), 8.08 (1H, t, J = 7.9 Hz, Ar H-6), 8.15–8.19 (1H, m, Ar H-4), 8.55 (1H, br s, Ar H-2), 9.81 (1H, br s,
CONHNH), 10.84 (1H, br s, CONHNH), 13C-NMR (DMSO-d6) : 125.7 (Ar C-2), 126.6 (Ar C-3), 129.0
(Ar C-5), 129.3 (Ar C-4), 129.6 (C-6), 132.6 (Ar C-1), 149.8 (triazole C-3), 153.1 (triazole C-5), 158.8
{NHC(=NH)NH}, 165.9 (CO). Anal. Calcd for C10H12N8O • 2HCl • 1.4H2O: C, 33.51; H, 4.72; N, 31.26.
Found: C, 33.43; H, 4.61; N, 31.43.
N'1,N'3-Bis(4,5-dihydro-1H-imidazol-2-yl)benzene-1,3-dicarbohydrazide Dihydrobromide (Bb)
A mixture of isophthaloyl chloride (0.50 g, 2.46 mmol) and 2-hydrazinoimidazoline hydrobromide (1.06
g, 5.86 mmol) in a round-bottomed flask was heated slowly up to 220 °C in an oil bath and kept for 3 min.
After cooling, the precipitate material was recrystallized from MeOH (5 mL) to give Bb (0.66 g, 54.5%).
Mp >245 °C (dec). IR (KBr) cm-1: 3227, 3154, 1690, 1658, 1618. FAB-MS (positive) m/z: 331 (M+H)+.
1H-NMR (DMSO-d6) : 3.69 (8H, s, imidazole H-4, H-5), 7.69 (1H, t, J = 7.9 Hz, Ar H-5), 8.14–8.16 (2H,
m, Ar H-4, H-6), 8.52 (1H, s, Ar H-2), 8.69 (4H, br, imidazole -NH-C=N+H-), 10.46 (2H, s, CONHNH),
10.92 (2H, s, CONHNH), 13C-NMR (DMSO-d6) : 42.8 (imidazole C-4, C-5), 127.7 (Ar C-2), 128.4 (Ar
C-5), 131.3 (Ar C-4, C-6), 131.9 (Ar C-1, C-3), 160.8 (imidazole C-2), 165.8 (CO). Anal. Calcd for
C14H18N8O2 • 2HBr • 1.6 H2O: C, 32.28; H, 4.49; N, 21.51. Found: C, 32.29; H, 4.68; N, 21.64.
3,3'-(1,3-Phenylene)bis(4H-1,2,4-triazol-5-amine) Dihydrochloride (Bd)
A mixture of isophthaloyl chloride (0.69 g, 3.40 mmol) and aminoguanidine hydrochloride (0.83 g, 7.51
mmol) in a round-bottomed flask was heated slowly up to 210 —240 °C in an oil bath and kept for 3.5 h.
After cooling, MeOH (30 mL) was added to the reaction mixture and separated insoluble material was
collected by filtration. The solid material was recrystallized from c-HCl. The crystal material was
dissolved in water and the aqueous solution was made alkaline with K2CO3. The precipitated material was

HETEROCYCLES, Vol. 83, No. 8, 2011
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filtered and purified by silica gel column chromatography with EtOH-28% ammonia solution (100 : 3) as
a solvent to afford Bd as a free base. Treatment with 10% methanolic hydrochloride (4 mL) gave Bd
dihydrochloride (0.45 g, 42.1%). Mp >240 °C (dec). IR (KBr) cm-1: 1689. FAB-MS (positive) m/z: 243
1
(M+H)+. H-NMR (DMSO-d6) : 7.0–9.0 (8H, br, NH + -N+H3), 7.72 (1H, t, J = 7.9 Hz, Ar H-5), 8.13
13
(2H, dd, J = 7.9, 1.8 Hz, Ar H-4, H-6), 8.52 (1H, t, J = 1.8 Hz, Ar H-2). C-NMR (DMSO-d6) : 123.3
(Ar C-2), 126.8 (Ar C-1, C-3), 128.0 (Ar C-4, C-6), 129.8 (Ar C-5), 149.1 (triazole C-3), 152.7 (triazole
C-5). Anal. Calcd for C10H10N8 • 2HCl • 0.2H2O: C, 37.68; H, 3.92; N, 35.15. Found: C, 37.81; H, 3.87;
N, 34.87.
2,2'-(1,3-Pyridinedicarbonyl)bis(hydrazinecarboximidamide) Dihydrochloride (Ca)
A mixture of pyridine-2,6-dicarbonyl dichloride (0.50 g, 2.45 mmol) and aminoguanidine hydrochloride
(0.67 g, 6.06 mmol) in a round-bottomed flask was heated slowly up to 145 °C in an oil bath and kept for
3 min. After cooling, the reaction mixture was triturated with water and concentrated in vacuo. The
solid residue was recrystallized from MeOH to give Ca (0.24 g, 27.9%). Mp 240 °C (dec). IR (KBr) cm-1:
1
3364, 3154, 1682. FAB-MS (positive) m/z: 280 (M+H)+. H-NMR (DMSO-d6) : 7.5–8.0 {8H, br,
C=(N+H2)NH2}, 8.27–8.28 (3H, m, Pyridine H-3, H-4, H-5), 10.07 (2H, s, CONHNH), 11.38 (2H, s,
13
CONHNH), C-NMR (DMSO-d6) : 125.3 (Pyridine C-3, C-5), 139.6 (Pyridine C-4), 147.4 (Pyridine
C-2, C-6), 158.9 {NHC(=NH)NH}, 163.0 (CO). Anal. Calcd for C9H13N9O2 • 2HCl • 1.5H2O: C, 28.51;
H, 4.78; N, 33.24. Found: C, 28.40; H, 4.55; N, 33.17.
N'2,N'6-Bis(4,5-dihydro-1H-imidazol-2-yl)pyridine-2,6-dicarbohydrazide
Hydrobromide • Hydrochloride (Cb)
A solution of pyridine-2,6-dicarbonyl dichloride (0.50 g, 2.45 mmol) and 2-hydrazinoimidazoline
hydrobromide (1.06 g, 5.86 mmol) in DMF (1 mL) was stirred at 130 °C for 3 min under an N2 stream.
After cooling, precipitated material was washed with AcOEt and dissolved in water (1 mL). Addition of
EtOH (1 mL) and isoPrOH (2 mL) to the solution gave Cb (0.62 g, 53.9%). Mp >240 °C. IR (KBr) cm-1:
1
3165, 1702, 1655, 1604. FAB-MS (positive) m/z: 332 (M+H)+. H-NMR (DMSO-d6) : 3.70 (8H, br s,
imidazole H-4, H-5), 8.29 (3H, s, Pyridine H-3, H-4, H-5), 8.7 (4H, br, imidazole -NH-C=N+H-), 10.67
(2H, br s, CONHNH), 11.57 (2H, s, CONHNH), 13C-NMR (DMSO-d6) : 42.8 (imidazole C-4, C-5),
125.5 (pyridine C-3, -5), 139.8 (Pyridine C-4), 147.2 (Pyridine C-2, C-6), 160.8 (imidazole C-2), 162.8
(CO). Anal. Calcd for C13H17N9O2 • 1.5HBr • 0.5HCl • 1.5H2O: C, 31.36; H, 4.45; N, 25.32. Found: C,
31.32; H, 4.64; N, 25.05.
2, 2’, 2’’-(1,3,5-Cylohexanetricarbonyl)tris(carboximidamide) Trihydrochloride (Da)
A mixture of 1,3,5-cis-cyclohexanetricarbonyl chloride9 (0.50 g, 1.84 mmol) and aminoguanidine
hydrochloride (0.73 g, 6.60 mol) in a round-bottomed flask was heated slowly up to 165 °C in an oil bath

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and kept for 5 min. After cooling, the precipitated solid material was washed with MeOH/EtOH to give
Da (0.53 g, 58.5%). Mp 248–250 °C (dec). IR (KBr) cm-1: 3363, 3141, 1662. FAB-MS (positive) m/z:
1
385 (M+H)+. H-NMR (DMSO-d6) : 1.40–1.48 (3H, dd, J = 15.5, 12.5 Hz, Cyclehexane HA-2, HA-4,
HA-6), 2.12 (3H, d, J =12.5 Hz, Cyclehexane HB-2, HB-4, HB-6), 2.50–2.51 (3H, m, Cyclohexane H-1,
H-3, H-5), 7.58–7.69 {12H, br, C=(N+H2)NH2}, 9.58 (3H, s, CONHNH), 10.21 (3H, s, CONHNH),
13C-NMR (DMSO-d6) : 30.0 (Cyclohexane C-2, C-4, C-6), 40.4 (Cyclohexane C-1, C-3, C-5), 158.6
{NHC(=NH)NH}, 174.1 (CO). Anal. Calcd for C12H24N12O3 • 3 HCl • H2O: C, 28.16; H, 5.71; N, 32.84.
Found: C, 28.25; H, 5.71; N, 32.86.
N'1,N'3,N'5-Tris(4,5-dihydro-1H-imidazol-2-yl)cyclohexane-1,3,5-tricarbohydrazide
Trihydrobromide (Db)
A mixture of 1,3,5-cis-cyclohexanetricarbonyl chloride9 (0.30 g, 1.10 mmol) and 2-hydrazinoimidazoline
hydrobromide (0.66 g, 3.65 mmol) in a round-bottomed flask was heated slowly up to 180 °C in an oil
bath and kept for 10 min. After cooling, the resulting mixture was washed with EtOH/isoPrOH to give Db
(0.31 g, 39.8%). Mp >250 °C. IR (KBr) cm-1: 3179, 1712, 1645. FAB-MS (positive) m/z: 463 (M+H)+.
1H-NMR (DMSO-d6) : 1.41–1.49 (3H, m, Cyclehexane ring HA-2, HA-4, HA-6), 2.12–2.14 (3H, m,
Cyclehexane ring HB-2, HB-4, HB-6), 2.31–2.37 (3H, m, Cyclehexane ring H-1, H-3, H-5), 3.64 (12H, s,
imidazole H-4, H-5), 8.50 (6H, br, imidazole -NH-C=N+H-), 10.26 (3H, s, CONHNH), 10.40 (3H, s,
CONHNH), 13C-NMR (DMSO-d6) : 30.0 (Cyclehexane ring C-2, C-4, C-6), 40.4 (Cyclehexane ring C-1,
C-3, C-5), 42.7 (imidazole C-4, C-5), 160.7 (imidazole C-2), 173.9 (CO). Anal. Calcd for C18H30N12O3 • 3
HBr: C, 30.66; H, 4.72; N, 23.83. Found: C, 30.82; H, 4.87; N, 23.90.
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