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KRUTIKOV et al.
vitro minimum inhibitory concentration values MIC100
were in the range of 6.2–25 μg mL. Compounds 2a–2z
and 2dd–2hh showed a high activity against herpes
virus type 1 and 2. In particular, amide 2j possessed
reliable virus inhibiting activity towards in vivo model
herpes pneumonia and was superior to Acyclovir at the
same dose (titer of virus lgCTD50 in the lungs of mice
for 3 days after infection for the reference compound,
2j, and Acyclovir was 3.6±0.15, 1.0±0.11 and
1.4±0.34, respectively). It was interesting to note that
compounds 2a, 2b, 2d–2i, 2k–2m, 2o–2v, and 2aa
moderately inhibited the strain of vesicular stomatitis
virus (Stomatitis vesicularis).
Phenylcarbamic acid esters 3a–3g were prepared
similarly.
Pentyl (4-chlorosulfonylphenyl)carbamate (4e).
Phenylcarbamic acid pentyl ester (20.7 g) was added
by portions with stirring to chlorosulfonic acid (50 g)
at 30–35°C. Then the reaction was slowly warmed to
50°C and kept at this temperature for 2 h. Next, the
reaction mixture was slowly poured into ice water with
vigorous stirring, while maintaining the reaction
mixture temperature no higher than 20°C. The
resulting precipitate was filtered off, washed with cold
water until the neutral filtrate (pH 7), and dried at
60°C. Yield 20.8 g (68%).
In summary, about a third of compounds obtained
are inducers of endogenous interferon, which confirms
desirability of searching for new antiviral drugs in a
series of substituted sulfonamides.
(4-Chlorosulfonylphenyl)carbamic acid esters 4a–
4e were prepared similarly.
Pentyl [4-(2,6-dichlorophenylsulfamoyl)-4-phenyl]-
carbamate (2j). To a mixture of 1.6 g of 2,6-
dichloroaniline and 1.6 g of pyridine heated to 85°C
was added in small portions at stirring 4 g of pentyl (4-
chlorosulfonylphenyl)carbamate 4e. The reaction
mixture was stirred for 1 h at 80°C, and then diluted
(1 : 1) with warm water (40°C). pH of the reaction
mixture was adjusted to 3.4 with hydrochloric acid.
After cooling to room temperature the resulting
precipitate was filtered off, washed with water,
recrystallized from 80% ethanol, and dried at 80°C.
Yield 3 g (70%).
EXPERIMENTAL
1H NMR spectra of the solutions in DMSO-d6 were
recorded on
a
Bruker WM-400 spectrometer
(400.13 MHz) using the residual proton signals of
DMSO as internal reference. Individuality of the
compounds obtained was monitored by HPLC (column
Luna C-18 4.6 × 250 mm, mobile phase: 0.1% solution
of trifluoroacetic acid in water (A), water–acetonitrile,
70 : 30 (B); flow rate 1.5 mL/min). Elemental analysis
was performed on analyzers Hewlett Packard B-185
and Leco CHNS-932. IR spectra were registered on a
FSM-1201 (KBr) and SHIMADZU FTIR-8400S
spectrometers. UV spectra were recorded on a 1700
PharmaSpec 230VCE UV spectrophotometer.
(4-Arylsulfamoyl-4-phenyl)carbamic acid esters
2a–2hh were prepared analogously. Physicochemical
characteristics of the target compounds are given in
Tables 1 and 3.
Pentyl
(4-sulfamoylphenyl)carbamate
(1).
Organic solvents and starting materials were
purified according to the known methods [9].
Compound 4e (3.06 g) was added in small portions to
50 mL of 25% aqueous ammonia with stirring, while
maintaining the reaction mixture temperature below
30°C. The mixture was then heated for 1 h at 60°C and
pH 9.5. After cooling to room temperature the
resulting precipitate was filtered off, washed with
water, and dried at room temperature. Yield 2.75 g
(96%).
Antiviral and antimycobacterial activity of the
target compounds was studied in relation to the
standard strains from the collection of the Department
of Microbiology of the Pavlov St. Petersburg First
State Medical University as described in [10].
Pentyl phenylcarbamate (3e). Pentan-1-ol (88 g)
was added dropwise with stirring to phenyl isocyanate
(119 g). The reaction mixture was stirred until
crystallization. Next, the mixture was allowed to stand
overnight at room temperature. The resulting product
was recrystallized from hexane and dried at 60°C.
Yield 190 g (92%).
Hydrolysis of pentyl (4-sulfamoylphenyl)
carbamate. A suspension of (4-sulfamoylphenyl)
carbamic acid pentyl ester 1 in 30% sodium hydroxide
was stirred until complete dissolution. The reaction
mixture was heated on a boiling water bath. The
reaction progress was monitored by TLC. The
hydrolysis of compound 1 was completed in 4 h.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 7 2016