Journal of Medicinal and Pharmaceutical Chemistry VOL. 2, No. 2 (19130)
Derivatives of 2-Styrylquinoline M. V. RUBTSOV, G. N. PERSHIN, N. A. YANBUKTIN, L. A. PELENITSINA, T. J. GUREVICH, N. A. NOVITSKAYA, S. N. MILOVANOVA and S. A. VICHKANOVA, Ordzhonikidze All- Union ChemicalPharmaceutical Research Institute, MOSCOW, U.S.S.R. Derivatives of 4-aminoquinoline have, as is well known, considerable antimalarial activity. The first representative of this series, 4-(6-diethylamino-a-methylbutylamino)-6-methoxyquinoline, obtained by one of us in collaboration with 0. Y. Magidson in 1937l possessed antimalarial activity very similar to that of quinine. Later, 4-(S-diethylamino-a-methylbutylamino)-7-chloroquinoline ( c h l ~ r o q u i n ewas ) ~ synthesized, which is even more active and can be used not only in malaria but also in the treatment of lupus erythematosus and of amcebal liver abscesses. I n contrast t o the derivatives of 4-aminoquinoline, the corresponding derivatives of 4-aminoquinaldine have no antimalarial properties.1 Thus, the introduction of a methyl group into the 2-position of the quinoline nucleus abolishes chemotherapeutic activity in these compounds. However, as it was shown by our studies, conversion of 4-aminoquinaldines t o the corresponding 2-styrylquinolines re-established and even increased antimalarial properties. Furthermore, we observed that such 2-styrylquinoline derivatives have pronounced activity not only against protozoa but also against bacteria, actinomycetes and fungi. This latter observation prompted us t o extend the investigation of compounds of this class and t o synthesize series of derivatives of 6-methoxy- and 7-chloro-2-styrylquinolines, with different substituents in the styryl group and in position 4 of the quinoline nucleus. The compounds obtained are listed in Tables I, 11, and 111. The styrylquinolines were prepared by condensation of the 8
113
M. V. RUBTSOV ET AL.
114
Table I. Derivatives of 4-(6-diethylamino-a-methylbutylamino)-6-methoxyqn~noline HN-CH-(CH,)
No.
1
aN(CSH,)S
Analysis
Number in Text
R
Yield
%
m.p. "C Calcd.
Found
I CI 1
2
I1
3
I11
4
IV
5
V
6
VI
-CJ
.3H,PO,
110-111
N, 7 . 4
N, 7.54
7
VI1
-C>OCH,
.3H,P04
75-76
P, 12.55
P, 12.84
71
g6-g8
N,5*67 p, 12.55
N,5.72 p, 12.00
67,2
'3H8P04
-
OCH,
I
8
VI11
OCH I
9
IX
.3H8P04
196-198
N,5.67
N,6*77
10
X
*3H8P04
130-132
N,5.32 p , 11.78
N,6*05 p, 11.2
66 66.3
DERIVATIVES O F 2-STYRYLQUINOLINE
No.
Number in Text
115
Analysis
R
m.p. "C
c--*------
Calcd.
a
Found
Yield
yo
OCOCH,
I
11
XI
12
XI1
-CH,CH,CH,
13
XI11
,CH,.3H,P04
N, 5.71
7o
98-100
N, 5.82 P, 10.75 N, 6.20 P, 13.74 N, 5533 P, 11.78
168-170
N, 5515
N,5.16
35.2
. 3 H a P 0 4 262-263
N, 5.55
N,5.24
56.7
, 3H3P04
172-175
.3H,P04
94-96
P, 10.61 N, 6.21
I?, 13.41 N, 5.49
P, 11.95
HOOC OCH, I I .3H,P04 OCH, I 15
XV
&OH
Table 11. Derivatives of 4-(S-diethylemino-cc-methylbutylamino)-7-chloroquinoline
HN-CH-(CH,)
I
~
No.
~~
,N(C,H,)
2
I
~
Number in Text
Analysis
R
m.p. "C
I
Yield
Calcd.
Found '
260-261
N, 7 . 9 5 C1, 26.84
N, 7.71 C1, 27.13
.3H,P04
196-198
N,5.6
N,5.64
89
.3H,P04
210-212
N,5.6
N,5,56
64
.3H,PO,
245-246
P , 12.22
P, 12.52
.2HCI
Yo
-
c1
XVII
-L> -cC1 I
XVIII XIX
O -s
-
75.5
M. V. RUBTSOV ET AL.
116
Table 11-cont. No.
Analysis
Number in Text
R
m.p. " c,
- A -
Yield
,
Calcd.
Found
yo
NO a
I
5
xx
-Q
6
XXI
7
XXII
.3H3P04
220-222
N, 7.30
N,7.39
90
iNoa 0
.3H3P04
248-250
N, 7.36
N,7.00
69
--\=)-OCH, I-\
.3H,P04
153-155
P, 12.48
P, 12.57
60
.3H,P04
160-163
N, 5.63
N.5.46
.3H,P04
143-146
N, 5 . 6 3 P, 12.48
N,5.44 P, 1 2 . 3
. 3H,P04
185-187
N, 5.28 P, 11.7
.3H,PO,
165-167
N, 5.29 P, 11.72
P, 11.64
.2HC1
257-260
N, 7.60 C1, 19.27
N, 8.04 C1, 19.02
.2HC1
167.5-169
N, 8.49 C1, 21.53
N,8.26 C1, 21.30
N(CH3),.3HC1
127-129
N, 9575 C1, 24.74
N, 9.75 C1, 24.88
138-1 40
N, 11.70 C1, 7 . 4 1
N, 11.72 C1,7.33
180
N, 5.12
N, 5.26
74
212-215
N, 5.52
N,5.21
63.2
OCH,
-e> I
8
XXIII
77.2
OCH, 9
--NHCOCH,
--SO,CH, OCOCH,
-h -/-> /-\
\,=
\=/-
95
N, 5.16
38
21.6
HOOC OCH,
I I 16 OCH,
I 17
X X X I I --OH -
DERIVATIVES O F 2-STYRYLQUINOLINE
117
Table 111. Derivatives of 2-(4-nitrostyryl)-6-methoxyquinoline
R CH,O-
No.
i\ 1
Number in Text
Ny-~~=~ Analysis
R
111.p.
"C
Yield
7-J-
%
Calcd.
Found
184-185
N, 8.45
N, 8.05
80
.H,PO,
253-255
N, 8 . 4 8
N, 8.20
60.7
.H,PO,
303.5-305
,N, 6,08 8.24
N, P, 7.85 6.31
I_____._______
-c1
1
XXXIII
2
XXXIV
-NH
3
XXXV
- N H C H E e )
-
-
4
XXXVI
5
XXXVII
-OCH,
181-183
N, 8.32
N,8.66
90.6
6
XXXVIII
-OC,H,
164-166
N, 7.99
N, 7.76
77
7
XXXIX
--OCH,-
