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BY (11) 9320
(13) C1
(46) 2007.06.30
(19)
(12)
(51)7 C 07D 239/42,
239/46, 403/12,
A 61K 31/505
,
(54)
(21)
: a 20000158
(22) 1998.07.21
(31) P 9701627 (32) 1997.07.21 (33) ES
(85) 2000.02.21
(86) PCT/ES98/00212, 1998.07.21
(87) WO 99/05121, 1999.02.04
(43) 2000.12.30
(71)
:
.
,
. (ES)
(72)
:
,
;
,
;
,
(ES)
(73)
:
.
,
(56) EP 0115713 A1, 1984.
WO 94/14779 A1.
EP 0497659 A1, 1992.
EP 0382637 A1, 1990.
(57)
1.
. (ES)
I:
R1
N
X
N
(I),
N
R2
N
S,
BY 9320 C1 2007.06.30
1
R
R2
,
1
,
4
1
,
6
3-6
N,
N,
,
,
,
5-
,
1
,
2
,
,
,
,
,
6-
,
, S
,
,S
,
6
,
,
,
6
,
1
,
3
,
N,
,
,
-
BY 9320 C1 2007.06.30
, 9,
,
,S
,
1
N,
5-6-
3
,
,
2
1
9,
.
2.
,
-
,
. 1,
S
N,
R1
,
-
.
3.
4.
. 1,
. 1,
,
,
R2
R2
. 1,
,
R2
. 1,
,
R2
.
.
5.
.
6.
3-
, 4-
, 3-
, 4, 3-
, 2. 1,
7.
1-
, 28.
3. 1,
, 3-2, 4-
, 3, 3-
R2
,
.
,
-2, 2-
, 3, 3-
, 2, 4-
. 1,
[b]
. 1,
)-1-
210.
2-[4-(22-[4-(2-2-[4-(242-(4-12-{4-[4-(4-
-
2-
,
, 2-
, 2.
,
R2
, 5[b]
.
9.
2-
2-2,
, 2, 2-
, 2,
R2
,
2-
.
,
,
]-4)-1)-1-
4-
:
,
]-4-
,
,
-2-[4-(2)-4-
)-1,
,
]-12-{4-[4-(4-
}-4-
,
]-1-
}-4-
,
2-(42-(42-[4-(22-[4-(242-[4-(5-
-1-
)-4-1-
)-4]-4-(
]-4-(
)-1)-1-2-[4-(34-2-
,
,
,
)-1-
,
-2-[4-(3-
)-1]-4-2-
)-12-[4-(5-
,
-2-[4-(3-
4-
,
-2-
,
,
)-1-
)-1-2-[4-(3-
4-
]-4,
-2-
)-1-
,
2-[4-(2-
[b]
)-12-[4-(2-
]-4-
,
[b]
)-1-
]-4-
,
2-[4-(22-[4-(3-
)-1-2[b]
2-[4-(3-2-
]-4)-1[b]
,
]-4-
,
)-1-
]-4-
,
4-
-2-[4-(2-
)-12
,
-
BY 9320 C1 2007.06.30
42-[4-(3-
4-2-[4-(24-2-
-2-[4-(2-
)-1-
,
)-1-
,
-2-[4-(2-
)-1)-12-[4-(3-
,
]-4-
,
-2-
)-1-
]-4-
,
2-[4-(32-[4-(32-[4-(32-[4-(54-
-22-[4-(3[b]
-22-[4-(5-2-[4-(44-
2-[4-(4-
)-1-2)-1-2)-1-2-[4-(4)-1-
42-[4-(3-
)-1-
42-[4-(2-
-2-[4-(3)-1-
44-
,
,
,
,
,
]-4-
,
]-4-
,
]-4-
-2-[4-(2)-1-
,
]-4-
,
,
)-1-
,
]-4-
,
)-1)-1-
4-1-2-{4-[4-(
,
]-4,
)-1-
]-4-
,
]-4-
,
)-1-
]-4)-1-
-1-
,
,
,
42-(44-
,
]-4-
)-1)-1-
2-[4-(2-2-[4-(2-2-(4-
,
]-4-
,
)-1-
2-[4-(22-[4-(2-
,
]-4-
)-1)-1-
)-12-[4-(3-2-[4-(24-
,
,
]-4-
2-[4-(32-[4-(3-
]-4-
]-4-
)-12-[4-(4-2-[4-(34-
,
)-1]-4]-4]-4)-1]-4)-1-
)-1)-1-
2-[4-(42-[4-(4-
]-4-
,
-2-(4-
-2-[4-(2-
)-1-
-1-
,
)-4-
,
]-14-
,
-2-{4-[4-(
]-1-
,
4-
-2-{4-[3-(
]-14-
,
-2-{4-[3-(
]-1-
,
4-
-2-{4-[2-(
]-14-
,
-2-{4-[2-(
]-1-
,
4-
-2-(44-
2-(4-
-1-2-(4-
,
-1-
-1-
)-4-1-
2-(42-[4-(12-(4-
,
)-4-
)-12-[4-(1-12-(4-
,
,
]-4)-1-
)-4-(
,
]-4-
,
,
-1-
)-4-(
3
,
BY 9320 C1 2007.06.30
4-
-2-[4-(2)-1,
4-2-[4-(2)-1,
4-2-[4-(2)-1,
4-2-[4-(2)-1,
2-[4-(3-2)-1]-4,
2-[4-(3-2)-1]-4,
4-2-{4-[2-(
]-1,
4-2-{4-[2-(
]-1,
2-[4-(2)-1]-4,
2-[4-(2)-1]-4,
2-[4-(4)-1]-4,
2-[4-(4)-1]-4,
4-2-{4-[2-(
]-1,
4-2-{4-[2-(
]-1,
2-[4-(3-2)-1]-4,
2-[4-(3-2)-1]-4,
2-[4-(
)-1]-4,
2-[4-(
)-1]-4,
4-2-[4-(4)-1,
4-2-[4-(4)-1,
2-[4-(2)-1]-4,
2-[4-(2)-1]-4,
2-[4-(2)-1]-4,
2-[4-(3-2)-1]-4,
2-[4-(3-2)-1]-4,
2-[4-(4-2)-1,
2-[4-(2)-1]-4,
2-[4-(2)-1]-4,
2-[4-(4-2)-1,
2-[4-(2)-1]-4,
4-2-[4-(2)-1]-44-2-[4-(2)-1.
11.
I
. 1,
,
III
R1
N
Cl ,
(III)
N
1
R
,
. 1,
IV
X
HN
,
N
R
2
R
,
(VI)
2
. 1,
.
12.
I
,
. 1,
V
4
BY 9320 C1 2007.06.30
R1
N
NH ,
N
(V)
N
1
R
,
. 1,
VI
R2
(VI)
,
R2
13.
,
. 1.
I
. 1,
,
V
R1
N
NH ,
N
(V)
N
R1
,
. 1,
VII
R2COY,
R2
,
(VII)
. 1,
Y
1-
14.
S,
, 2,4-
.
I
(4-
. 1,
I,
-2,4-
)-1,3,2,4-
-
.
15.
I
. 1,
I
.
16.
,
,
,
,
,
,
,
,
-
I
. 1-10
.
17.
I
-
I
-
. 1-10
,
,
,
,
,
.
18.
. 1-10
,
,
,
,
,
.
5
BY 9320 C1 2007.06.30
(I),
,
,
-
,
.
R1
N
X
N
,
N
(I)
2
R
N
,
,
.
382637
497659
(II)
.
N
N
N
-0115713
4
,
R.
(CH2)n
(II)
N
,
(
-1)-2-
-
,
-
,
,
,
.
WO 94/14779
4
,
(
-1)-4-
-
,
4
,
,
5-
,
1,
(
).
4547505
-
,
,
,
,
-
,
,
.
4
(I).
,
.
,
,
.
,
,
,
.
1
,
.
6
BY 9320 C1 2007.06.30
,
-
,
,
,
ics,
,
,
,
, antitusigen-
,
,
,
,
,
,
-
,
.
(I):
R1
N
X
N
,
N
(I)
R2
N
S,
R1
R2
,
1
,
4
1
,
6
3-6
N,
1
,
,
,
,
, 9,
5,
,
,
,
,
,S
,
,
6-
,
,
,
,S
,
6
,
,
2
1
,
6
,
N,
3
,
N,
,
,
,
,
S
,
N,
1
5-6
3
,
,
OR3,
R1
9-
1
4
R2
S
,
1
,
R2
3-6
3-6
,
-
,
,
,
6
1
R2
,
,
.
R2
,
,
, 4, 3-
,
R2
N,
,
,
,
, 2-
1, 2
,
,
, 2, 2-
, 4-
-
3
,
,
,
, 4-
, 3, 2-(
,
3
1
,
",
, 2-
, 3, 2-
.
,
"
-
,
,S
.
,
6
,
,
2-
6
.
3
,
N,
,
4
,
,
-
,
1
,
.
,
2
.
1
R3
-
,
3-
,
7
,
:
,
,
, 1-
BY 9320 C1 2007.06.30
,
,
,
,
R2
5-
9
10
,
, 3-
4-
,
-
N,
,
S,
,
, 3,
,
,
-2, 2-
, 3-
,
61
2
,
,
,
-2-
,
.
,
, 5[b]
,
,
2-
-2-
,
,
, 2, 2-
, 2,
,
R2
,
, 3, 3.
,
,
1
3
,
,
",
,
[b]
2-
"
2-
.
(I)
,
-
,
.
(I)
,
,
,
.
-
.
(I),
,
,
,
,
,
,
,
.
(I),
R1
X
,
R2
-
,
.
:
(III),
(I)
1
R
(IV),
,
R2
X
:
R1
R1
N
N
X
Cl + HN
N
R2
N
N
R2 .
N
(IV)
(III)
X
N
(I)
,
,
,
-
,
,
1,2,
,
,
-
,
,
,
-
.
,
N-
,
,
,
-
,
,
,
.
8
BY 9320 C1 2007.06.30
:
(I)
(V):
R1
N
NH ,
N
(V)
N
R1
R2COOH (VI),
,
,
R2
,
R1
-
R2COY (VII):
R1
N
N
N
O
R2COOH
NH
N
o R2COY
N
N
R2 .
N
(I)
(V)
,
,
,
,
,
.
-
,
,
R2COY (VII)
,
Y
,
1-
,
.
,
,
-
(I)
(V)
(VI).
,
,
,
N,N'-
,
3-(31-
-1-
N-
-
.
.
(VI)
(V)
N,N'.
,
,
,
-
,
1,2,
,
,
-
,
,
,
.
,
,
-
,
N-
,
,
,
.
(I) ,
,
X
,
X
(I),
R1
2,4- (49
R2
S, R1
.
)-1,3,2,4-
R2
-
BY 9320 C1 2007.06.30
-2,4,
X
S:
R1
R1
N
N
O
N
S
N
N
R
N
N
2
R2 .
N
,
,
,
,
.
,
,
-
,
,
,
80 °
.
D:
(I)
,
,
,
,
,
,
,
,
,
,
,
,
,
,
-
.
,
,
,
,
,
,
,
,
(I)
-
.
(I)
,
,
,
-
,
,
.
,
,
,
,
,
,
.
,
.
-
,
,
.
:
1.
1,0
2-[4-(2-
(6,92
) 21,39
-4(13,84
)-1, 1,49
)
]-4-
(8,30
20
) 1-(2-
.
.
Na2SO4
,
,
-
70 : 30
,
,
.
,
)-1-
]-4-
,
10
1,4
(4,86
. = 85-86 ° .
) 2-[4-(2-
BY 9320 C1 2007.06.30
:
3.
1,0
4-
(5,15
)
(5,18
) 430
1
l2
0°
.
Na2SO4
1,0
(3,28
)
,
. = 71-73 ° .
4-
12.
10
-2-[4-(2-
.
,
)-1-
-2-[4-(3-
)-1-
4-
1,0 (7,81
) 330
CH2Cl2,
.
1,5 (7,81
) 4CH2Cl2.
1
0,84
0° ,
0°
-2-(1-
(7,86
(7,81
)
)
,
,
2
Na2SO4
,
.
,
[4-(3-
)-10,83 (5,15
)
0,83 (5,15
) N,N'1,0 (5,15
) 42
) 4)-1-
-2-
]-4-
.
-2-(1.
,
)-1-
4) 2-(4-
]-4-
-2-(4-10,46
)-1,3,2,416
-2-
15
30
.
) 2-[4-(2203 ° .
25
(480-90 °
0,8 (2,63
. 90-92 ° .
,
2-[4-(2-
20.
54.
(1,9
,
,
2
(2,4-
-
20
2
0,56
(7,18
0,76
-
0°
.
,
)-1-
-2-(1-
) 22
-2-[4-(2-
,
-1]-4(1,14
-2,4-
1,7 (5,04
. = 202-
)
).
.
-
,
Na2SO4,
.
160
(0,5
. 125-129 ° .
) 2-(4-
-1-
D:
2.
1,0 (3,47
2-[4-(2) 2-[4-(2,
)-1-
)-1,
,
11
,
,
)-4-
]-4,
]-4,
BY 9320 C1 2007.06.30
1,07
(3,29
,
)
. = 162-164 ° .
2-[4-(2-
4.
1,0
4-
(3,29
) 4,
(3,08
1,05
-2-[4-(2,
,
,
)
. = 143-145 ° .
,
44-
(2,63
) 4-
-2-[4-(3,
0,6
,
)-1-
]-4-
-2-[4-(2-
)-1-
)-1-
13.
0,8
)-1-
,
-2-[4-(2-2-[4-(3-
)-1-
)-1-
,
(1,76
,
,
)
. = 154-156 ° .
,
4-
-2-[4-(3-
.1
mSdHz MHz -
)-1-
:
,
tdd broad broad singlet -
,
,
,
12
,
,
,
.
1
R1
N
X
N
N
R2
N
-
R2
-
X
O
1
3
-
-
O
2
3
-
O
HCl
D
13
3
S
3
-
-
S
4
5
3
3
-
-
HCl
3
O
D
-
. (° )
1
(
)(
)δ
(300 MHz) (CDCl3) 3.90 (broad singlet, 11 ),
6.04 (d, J = 5.5 Hz, 1H), 6.51 (dd, J = 3.5 Hz,
85-86
J' = 1.7 Hz, 1H), 7.05 (d, J = 3.5 Hz, 1H), 7.51
(broad singlet, 1H), 8.07 (d, J = 5.5 Hz, 1H).
(300 MHz) (DMSO-d6) 3.83 (m, 4H), 3.91 (m,
4H), 3.95 (s, 3H), 6.36 (d, J = 6.3 Hz, 1H),
162-164
6.66 (m, 1H), 7.07 (m, 1H), 7.88 (m, 1H), 8.16
(d, J = 6.3 Hz, 1H).
(300 MHz) (CDCl3) 3.83 (m, 4H), 3.89 ( .,
7H, (δ = 3.89, s)), 6.04 (d, J = 5.7 Hz, 1H),
71-73 7.07 (dd, J = 5.1 Hz, J' = 3.9 Hz, 1H), 7.33 (d,
J = 3.9 Hz, 1H), 7.48 (d, J = 5.1 Hz, 1H), 8.07
(d, J = 5.7 Hz, 1H).
(300 MHz) (DMSO-d6) 3.80 (m, 4H), 3.91 (m,
4H), 3.95 (s, 3H), 6.37 (d, J = 6.5 Hz, 1H),
143-145 7.15 (dd, J = 4.9 Hz, J' = 3.6 Hz, 1H), 7.49 (dd,
J = 3.6 Hz, J' = 1.2 Hz, 1H), 7.80 (dd, J = 4.9
Hz, J' = 1.2 Hz, 1H), 8.15 (d, J = 6.5Hz, 1H).
(300 MHz) (CDCl3) 2.15 (s, 3H), 3.52 (m, 2 ),
119-120 3.68 (m, 2H), 3.83 (m, 4H), 3.89 (s, 3 ), 6.02
(d, J = 5.7 Hz, 1H), 8.06 (d, J = 5.7 Hz, 1H).
,
-1
(KBr) 1623, 1598,
1583, 1561, 1502,
1439, 1264, 1025.
(KBr) 2800-2200
(broad), 1642, 1605,
1483, 1262.
(KBr) 1598, 1561,
1432, 1257, 989.
(KBr) 2800-2203
(broad), 1637, 1614,
1597, 1484, 1437,
1409, 1210.
(KBr) 1654, 1595,
1561, 1423, 1345,
1249, 988.
BY 9320 C1 2007.06.30
R1
Cl
N
6
3
-
-
N
(CH2)3
N
7
3
-
HCl
N
D
(CH2)3
8
3
-
3
-
-
9
-
14
O
10
-
CF3-
S
11
CF3-
O
-
S
12
3
-
O
-
B
(film) 1651, 1644,
1588, 1470, 1339.
(KBr) 2800-2200
(broad), 1641, 1610,
1484, 1437, 1353,
1270, 1216.
(KBr) 1625, 1606,
1597, 1558, 1461,
1428, 1266, 988.
(KBr) 1638, 1589,
1567, 1470, 1444,
1335, 1235, 1225.
(KBr) 1620, 1592,
1509, 1332, 1268,
1138.
(KBr) 1594, 1521,
1430, 1336, 1262,
1151.
(KBr) 1623, 1595,
1582, 1561.
BY 9320 C1 2007.06.30
Cl
(300 MHz) (CDCl3) 2.21 (m, 2H), 2.32 (m,
2H), 3.45 (m, 2H), 3.68 (m, 2H), 3.80 (m, 4H),
aceite 3.89 (s, 3H), 4.20 (t, J = 6.5 Hz, 2H), 6.03 (d,
J = 5.7 Hz, 1H), 7.40 (s, 1H), 7.42 (s, 1H), 8.05
(d, J = 5.7 Hz, 1H).
(300 MHz) (DMSO-d6) 1.98 (q, J = 6.9 Hz,
2H), 2.33 (t, J = 7.0 Hz, 2H), 3.57 (m, 4H),
148-149 3.82 (m, 4H), 3.95 (s, 3H), 4.10 (t, J = 6.9 Hz,
2H), 6.36 (d, J = 6.6 Hz, 1H), 7.50 (s, 1H),
7.98 (s, 1H), 8.14 (d, J = 6.6 Hz, 1H).
(300 MHz) (CDCl3) 3.52 (m, 2H), 3.73-4.00
99-102
., 9H, (δ = 3.88, s)), 6.03 (d, J = 5.5 Hz,
1H), 7.44 (s, 5H), 8.06 (d, J = 5.5 Hz, 1H).
(300 MHz) (CDCl3) 0.80 (m, 2H), 1.02 (m,
2H), 1.78 (m, 1H); 3.68-3.92 ( ., 11H,
76-78
(δ = 3.89, s)), 6.02 (d, J = 5.7 Hz, 1H), 8.06 (d,
J = 5.7 Hz, 1H).
(300 MHz) (CDCl3) 3.84-4.00 ( ., 8H), 6.51
(dd, J = 3.5 Hz, J' = 1.7 Hz, 1H), 6.82 (d,
112-113 J = 4.8 Hz, 1H), 7.06 (dd, J = 3.5 Hz, J' = 1.0
Hz, 1H), 7.51 (dd, J = 1.7 Hz, J' = 1.0 Hz, 1H),
8.51 (d, J = 4.8 Hz, 1H).
(300 MHz) (CDCl3) 3.86 ( ., 4 ), 3.96 ( .,
), 6.82 (d, J = 4.8 Hz, 1H), 7.08 (dd, J = 5.0
136-137 Hz, J' = 3.7 Hz, 1H), 7.34 (dd, J = 3.7 Hz,
J' = 1.1 Hz, 1H), 7.48 (dd, J = 5.0 Hz, J' = 1.1
Hz, 1H), 8.52 (d, J = 4.8 Hz, 1H).
(300 MHz) (CDCl3) 3.72 (m, 4H), 3.80-3.96
.., 7H, (δ = 3.89, s)), 6.03 (d, J = 5.6 Hz, 1H),
90-92 7.22 (d, J = 5.0 Hz, 1H), 7.36 (m, 1H), 7.56
(broad singlet, 1H), 8.06 (d, J = 5.6 Hz, 1H).
13
14
3
3
-
-
O
S
H3C
D
(300 MHz) (CDCl3) 2.51 (s, 3H), 3.79-3.93
., 11 , (δ = 3.89, s)), 6.03 (d, J = 5.6 Hz,
90-92
1H), 6.72 (m, 1H), 7.15 (d, J = 3.5 Hz, 1H),
8.06 (d, J = 5.6 Hz, 1H).
(300 MHz) (CDCl3) 2.46 (s, 3H), 3.79 (m, 4H),
3.91 (m, 4H), 3.95 (s, 3H), 6.37 (d, J = 6.4 Hz,
115-119
1H), 6.84 (m, J = 3.6 Hz, 1H), 7.29 (d, J = 3.6
Hz, 1H), 8.14 (d, J = 6.4 Hz, 1H).
(300 MHz) (CDCl3) 3.69 ( ., 4 ), 3.85-3.93
., 10 , (δ = 3.90, two singlets)), 6.02 (d,
99-101 J = 5.7 Hz, 1H), 6.80 (d, J = 5.6 HZ, 1H), 7.37
(d, J = 5.6 Hz, 1H), 8.07 (d, J = 5.7 Hz, 1H).
-
D
(300 MHz) (DMSO-d6) 3.60 ( ., 4 ), 3.82- (KBr) 2800-2200
3.90 ( ., 7 , (δ = 3.88, s)), 3.94 (s, 3 ), 6.33 (broad), 1640, 1610,
162-165 (d, J = 6.3 Hz, 1H), 7.04 (d, J = 5.6 Hz, 1H),
1479, 1442, 1406.
7.69 (d, J = 5.6 Hz, 1H), 8.14 (d, J = 6.3 Hz, 1H).
-
O
15
3
HCl
S
H3C
O
HCl
15
S
16
3
-
-
O
O
CH3
S
17
3
-
O
O
18
19
3
3
-
-
HCl
CH3
S
S
-
O
O
HCl
D
(300 MHz) (CDCl3) 3.86 (m, 4H), 3.90 (s, 3H),
3.92 (m, 4H), 6.05 (d, J = 5.7 Hz, 1H), 7.42
173-174
., 2H), 7.53 (s, 1H), 7.85 ( ., 2H), 8.07 (d,
J = 5.7 Hz, 1H).
(300 MHz) (DMSO-d6) 3.84 (m, 4H), 3.893.97 ( ., 7H, (δ = 3.93, s)), 6.32 (d, J = 6.3
155-156
Hz, 1H), 7.45 ( ., 2H), 7.81 (s, 1H), 7.94 (m,
1H), 8.02 (m, 1H), 8.15 (d, J = 6.3 Hz, 1H).
(KBr) 1625, 1590,
1562, 1510, 1471,
1414, 1261.
(KBr) 2800-2200
(broad), 1641, 1615,
1602, 1488, 1412,
1260.
(KBr) 1623, 1594,
1656.
(KBr) 1604, 1589,
1559, 1459, 1259, 991.
(KBr) 2800-2200
(broad), 1644, 1611,
1487.
BY 9320 C1 2007.06.30
D
(300 MHz) (DMSO-d6) 3.66 (m, 4H), 3.87 (m, (KBr) 2800-2200
4H), 3.92 (s, 3H), 6.32 (d, J = 6.1 Hz, 1H),
(broad), 1642, 1617,
154-156 7.24 (m, 1H), 7.63 (broad singlet, 1H), 7.85
1598.
(broad singlet, 1H), 8.14 (d, J = 6.1 Hz, 1H).
S
20
3
-
NH
-
O
Cl
21
3
-
-
O
S
22
Cl
3
-
O
HCl
D
164-165
16
S
23
3
-
-
O
142-143
N
H
24
3
-
O
HCl
D
N
H
25
3
S
26
3
S
CH2-
CH2-
-
O
O
HCl
180-182
(dec)
69-71
D
172-175
(300 MHz) (DMSO-d6) 3.45-4.00 ( ., 11H,
(δ = 3.91, s)), 6.31 (d, J = 6.4 Hz, 1H), 7.60
., 2H), 7.88 (m, 1H), 8.12-8.18 ( ., 2H,
(δ = 8.15, d, J = 6.4 Hz)).
(300 MHz) (CDCl3) 3.90 (s, 3H), 3.92 ( .,
8H), 6.03 (d, J = 5.6 Hz, 1H), 6.26 (m, 1H),
6.56 (m, 1H), 6.94 (m, 1H), 8.07 (d, J = 5.6
Hz, 1H), 9.87 (m, 1H).
(300 MHz) (DMSO-d6) 3.86 ( ., 4 ), 3.94
(m, 4H), 3.97 (s, 3 ), 6.13 (m, 1H), 6.41 (d,
J = 6.7 Hz, 1H), 6.56 (m, 1H), 6.90 (m, 1H),
8.15 (d, J = 6.7 Hz, 1H), 11.52(m, 1H).
(300 MHz) (CDCl3) 3.57 (m, 2H), 3.72 (m,
4H), 3.80 (m, 2H), 3.88 (s, 3H), 3.97 (s, 2H),
6.02 (d, J = 5.7 Hz, 1H), 6.95 (m, 2H), 7.21
(m, 1H), 8.05 (d, J = 5.7 Hz, 1H).
(300 MHz) (DMSO-d6) 3.63 (m, 2H), 3.70 (m,
2H), 3.83 (m, 4H), 3.96 (s, 3H), 4.03 (s, 2H),
6.38 (d, J = 6.6 Hz, 1H), 6.96 (m, 2H), 7.39
(dd, J = 4.8 Hz, J' = 1.7 Hz, 1H), 8.15 (d,
J = 6.6 Hz, 1H).
(KBr) 3260, 1605,
1578, 1571, 1438,
1336, 1251.
(KBr) 1638, 1588,
1564, 1263.
(KUr) 2800-2200
(broad), 1640, 1629,
1625, 1609, 1418,
1219.
(KBr) 3258, 1586,
1566, 1467, 1433.
(KBr) 3162, 28002200 (broad), 1630,
1605, 1487, 1428.
(KBr) 1634, 1561,
1440, 1337, 1236.
(KBr) 2800-2200
(broad), 1667, 1636,
1606, 1411, 1216,
1208.
BY 9320 C1 2007.06.30
(300 MHz) (CDCl3) 3.92 (s, 3H), 3.93-4.10
., 8H), 6.05 (d, J = 5.6 Hz, 1H), 6.83 (d,
J = 1.4 Hz, 1H), 7.15 (t, J = 7.3 Hz, 1H), 7.30
202-203
(t, J = 7.3 Hz, 1H), 7.45 (d, J = 8.3 Hz, 1H),
7.67 (d, J = 8.3 Hz, 1H), 8.09 (d, J = 5.6 Hz,
1H), 9.42 (broad singlet, 1H).
(300 MHz) (CDCl3) 3.59 (m, 2H), 3.88 (s, 3H),
3.92 (m, 6H), 6.04 (d, J = 5.6 Hz, 1H), 7.50
175-176
., 2H), 7.86 ( ., 2H) 8.06 (d, J = 5.6 Hz,
1H).
S
27
3
-
-
O
87-89
CH3
28
3
-
O
HCl
D
(300 MHz) (DMSO-d6) 3.62 (m, 4H), 3.89 (m,
4H), 3.94 (s, 3H), 6.37 (d, J = 6.6 Hz, 1H),
144-146 6.95 (d, J = 4.9 Hz, 1H), 7.60 (d, J = 4.9 Hz,
1H), 8.14 (d, J = 6.6 Hz, 1H).
(KBr) 2800-2200
(broad), 1617, 1604,
1486, 1427, 1413,
1258.
CH3
29
S
3
-
-
O
86-88
(300 MHz) (CDCl3) 3.55-3.85 ( ., 4 ), 3.89 (KBr) 1622, 1587,
(s, 3H), 3.91 (m, 4H), 6.04 (d, J = 5.7 Hz, 1H), 1561, 1509.
6.94 (d, J = 5.1 Hz, 1H), 7.40 (d, J = 5.1 Hz,
1H), 8.07 (d, J = 5.7 Hz, 1H).
17
Cl
S
30
3
-
O
HCl
D
Cl
31
3
-
O
-
NH
CH2-
32
3
-
O
S
-
(300 MHz) (DMSO-d6) 3.50-3.70 ( ., 4 ),
(KBr) 2800-2200
3.87 (m, 4H), 3.91 (s, 3H), 6.31 (d, J = 6.2 Hz, (broad), 1636, 1608,
144-147
), 7.14 (d, J = 5.4 Hz, 1H), 7.85 (d, J = 5.4 1481, 1443, 1407.
Hz, 1H), 8.14 (d, J = 6.2 Hz, 1H).
(300 MHz) (CDCl3) 3.80 (m, 4H), 3.84-3.93
., 7 , (δ = 3.88, s)), 6.03 (d, J = 5.7 Hz,
229-231 1H), 7.22 (m, 2H), 7.38 (m, 1H), 7.46 (d,
J = 2.8 Hz, 1H), 7.73 (m, 1H), 8.07 (d, J = 5.7
Hz, 1H), 8.96 (broad singlet, 1H).
(300 MHz) (CDCl3) 3.53 (m, 2H), 3.66 (m,
2H), 3.78 ( ., 4H), 3.86 (s, 3H), 3.98 (s, 2H),
135-137 6.01 (d, J = 5.6 Hz, 1H), 7.26 (s, 1H), 7.40 (m,
2H), 7.85 (m, 2H), 8.03 (d, J = 5.6 Hz, 1H).
(KBr) 3181, 1610,
1590, 1559, 1467,
1339, 998.
(KBr) 1619, 1590,
1561, 1553, 1454, 990.
BY 9320 C1 2007.06.30
S
(300 MHz) (CDCl3) 2.29 (s, 3H), 3.68 (m, 4H), (KBr) 1634, 1586,
3.86 (m, 4H), 3.88 (s, 3H), 6.03 (d, J = 5.6 Hz, 1567, 1468, 1453,
1H), 6.86 (d, J = 5.0 Hz, 1H), 7.30 (d, J = 5.0 1260.
Hz, 1H) 8.06 (d, J = 5.7 Hz, 1H).
Cl
33
34
3
3
-
-
-
-
O
Cl
CH3O
S
O
HCl
D
-
O
18
(300 MHz) (CDCl3) 3.81 (m, 4H), 3.89 (m,
4H), 3.90 (s, 3H), 6.04 (d, J = 5.7 Hz, 1H),
99-100
6.89 (d, J = 4.0 Hz, 1H), 7.13 (d, J = 4.0 Hz,
1H), 8.07 (d, J = 5.7 Hz, 1H).
(300 MHz) (DMSO-d6) 3.80 (m, 4H), 3.91 (m,
4H), 3.94 (s, 3H), 6.35 (d, J = 6.3 Hz, 1H),
159-162 7.18 (d, J = 4.0 Hz, 1H), 7.40 (d, J = 4.0 Hz,
1H), 8.15 (d, J = 6.3 Hz, 1H).
(KBr) 1610, 1594,
1584, 1561, 1442,
1258.
(300 MHz) (CDCl3) 3.58-3.96 ( ., 14 ,
(δ = 3.84, s, δ = 3.87, s)), 6.02 (d, J = 5.7 Hz,
1H), 6.92 (m, J = 8.8 Hz, 2H), 7.41 (m, J = 8.8
Hz, 2H), 8.05 (d, J = 5.7 Hz, 1H).
(300 MHz) (CDCl3) 3.76-3.88 ( ., 7 ,
(δ = 3.85, s)), 3.93-4.36 ( ., 7 , (δ = 4.07,
s)), 6.29 (d, J = 6.8 Hz, 1 ), 6.93 (d, J = 8.6
Hz, 2H), 7.40 (d, J = 8.6 Hz, 2H), 8.10 (d,
J = 6.8 Hz, 1H).
(300 MHz) (CDCl3) 3.37-4.03 ( ., 11 ,
(δ = 3.89, s)), 6.04 (d, J = 5.7 Hz, 1H), 7.12
(m, J = 8.8 Hz, 2H), 7.46 (m, J = 8.8 Hz,
J' = 5.4 Hz, 2H), 8.06 (d, J = 5.7 Hz, 1H).
(300 MHz) (CDCl3) 3.80 (m, 4H), 3.98-4.28
., 7 , (δ = 4.07, s)), 6.31 (d, J = 6.8 Hz,
1H), 7.13 (t, J = 8.6 Hz, 2H), 7.44 (dd, J = 8.6
Hz, J' = 5.3 Hz, 2H), 8.11 (d, J = 6.8 Hz, 1H).
(KBr) 1624, 1587,
1562, 1433, 1252.
127-129
36
3
37
38
39
3
3
3
-
-
-
-
CH3O
F
F
Cl
O
HCl
-
O
O
O
D
HCl
123-126
D
-
162-164
152-156
(300 MHz) (CDCl3) 3.50 (m, 2H), 3.66-4.01
., 9 , (δ = 3.89, s)), 6.04 (d, J = 5.6 Hz,
143-144
1H), 7.40 (system AB, J = 8.7 Hz, 4H), 8.06
(d, J = 5.6 Hz, 1H).
(KBr) 2800-2200
(broad), 1639, 1613,
1592,1436.
(KBr) 2800-2200
(broad), 1631, 1615,
1484, 1428, 1413,
1260, 1244.
(KBr) 1631, 1584,
1565, 1428, 1340,
1249.
(KBr) 2800-2200
(broad), 1630 (banda
intensa), 1485, 1439,
1415, 1355, 1266,
1005.
(KBr) 1630, 1580,
1558, 1470, 1439,
1262.
BY 9320 C1 2007.06.30
35
3
S
40
3
-
O
Cl
HCl
D
CH3
O
3
-
-
O
42
CH3
O
3
-
O
HCl
D
(300 MHz) (CDCl3) 3.61-4.38 ( ., 14H,
(δ = 3.83, s and δ = 4.08, s)), 6.30 (d, J = 6.9
158-161 Hz, 1H), 6.96 ( ., 3H), 7.34 (t, J = 8.1 Hz,
1H), 8.10 (d, J = 6.9 Hz, 1H).
(KBr) 2800-2200
(broad), 1636, 1605,
1490, 1418, 1270.
(300 MHz) (CDCl3) 3.49 (m, 2 ), 3.66-4.02
., 9 , (δ = 3.89, s)), 6.04 (d, J = 5.6 Hz,
106-107
1H), 7.19 ( ., 3 ), 7.41 (m, 1 ), 8.06 (d,
J = 5.6 Hz, 1H).
(300 MHz) (CDCl3) 3.56-4.43 ( ., 11 ,
(δ = 4.09, s)), 6.32 (d, J = 6.9 Hz, 1H), 7.18
153-156
., 3H), 7.43 (m, 1H), 8.11 (d, J = 6.9 Hz, 1H).
(KBr) 1639, 1593,
1582, 1459, 1439,
1342.
19
(KBr) 2800-2200
(broad), 1631, 1609,
1492, 1431, 1420,
1359, 1262.
(KBr) 1630, 1584,
1562, 1430, 1338,
1236.
F
43
3
-
-
O
F
44
3
-
O
HCl
D
Cl
45
3
-
-
O
94-96
Cl
46
3
-
O
HCl
D
(KBr) 2800-2200
(broad), 1639, 1610,
1489, 1415, 1288,
1266.
(300 MHz) (CDCl3) 3.49 (m, 2H), 3.70-4.00
(KBr) 1645, 1593,
., 9 , (δ = 3.89, s)), 6.04 (d, J = 5.7 Hz, 1H), 1561, 1433, 1256.
7.29-7.45 ( ., 4 ), 8.07 (d, J = 5.7 Hz, 1H).
(300 MHz) (CDCl3) 3.60-3.97 ( ., 4 ), 3.984.37 ( ., 7 , (δ = 4.08, s)), 6.31 (d, J = 7.0
166-170
Hz, 1H), 7.29 (m, 1H), 7.42 ( ., 3H), 8.11 (d,
J = 7.0 Hz, 1H).
(KBr) 2800-2200
(broad), 1632, 1611,
1597, 1488, 1414,
1286.
BY 9320 C1 2007.06.30
41
(300 MHz) (CDCl3) 3.80 (m, 4H), 3.97-4.38
., 7H, (δ = 4.09, s)), 6.32 (d, J = 6.9 Hz,
166-168
1H), 7.37 and 7.43 (system AB, J = 8.6 Hz,
4H), 8.11 (d, J = 6.9 Hz, 1H).
(300 MHz) (CDCl3) 3.50 (m, 2H), 3.66-4.02
., 12 , (δ = 3.83, s δ = 3.88, s)), 6.03 (d,
78-81 J = 5.6 Hz, 1H), 6.99 ( ., 3H), 7.33 (t, J = 8.0
Hz, 1H), 8.06 (d, J = 5.6 Hz, 1H).
H3 C
O
47
3
-
-
O
H3 C
O
48
3
-
O
HCl
D
49
3
-
-
O
50
F
20
3
-
O
HCl
D
Cl
51
3
-
-
O
Cl
52
3
-
O
HCl
D
O
53
3
-
O
-
(KBr) 1619, 1584,
1562, 1241.
(300 MHz) (CDCl3) 3.40 (broad, 2H), 3.773.98 ( ., 9H, (δ = 3.89, s)), 6.03 (d, J = 5.6 Hz,
102-103
1H), 7.12 (m, 1H), 7.23 (m, 1H), 7.42 (m, 2H),
8.06 (d, J = 5.6 Hz, 1H).
(300 MHz) (CDCl3) 3.58 (broad, 2H), 3.824.39 ( ., 9 , (δ = 4.08, s)), 6.31 (d, J = 6.9
148-152
Hz, 1H), 7.13 (m, 1H), 7.25 (m, 1H), 7.44 (m,
2H), 8.11 (d, J = 6.9 Hz, 1H).
(300 MHz) (CDCl3) 3.32 (m, 2H), 3.71-4.00
., 9H, (δ = 3.88, s)), 6.03 (d, J = 5.6 Hz, 1H),
112-115
7.30-7.46 ( ., 4H), 8.06 (d, J = 5.6 Hz, 1H).
(KBr) 1641, 1595,
1561, 1466.
(KBr) 2800-2200
(broad), 1644, 1628,
1611, 1490, 1261.
(KBr) 2800-2200
(broad), 1643, 1612,
1490, 1430, 1418,
1287, 1260.
(KBr) 1640, 1593,
1561.
(300 MHz) (CDCl3) 3.49 (m, 2H); 3.73-4.40
(KBr) 2800-2200
., 9H, (δ = 4.08, s)), 6.30 (d, J = 6.7 Hz, 1H), (broad), 1643, 1609,
152-154
7.25-7.48 ( ., 4H), 8.10 (d, J = 6.7 Hz, 1H). 1492, 1431, 1415,
1288, 1258.
(300 MHz) (CDCl3) 1.82-2.13 ( ., 3H), 2.31 (KBr) 1653, 1596,
(m, 1H), 3.58 (m, 2H), 3.67-3.82 ( ., 4H),
1586, 1564, 1505,
1239, 987.
90-91 3.82-3.98 ( ., 7H, (δ = 3.87, s)), 4.63 (dd,
J = 7.4 Hz, J' = 5.3 Hz, 1H), 6.00 (d, J = 5.6
Hz, 1H), 8.03 (d, J = 5.6 Hz, 1H).
BY 9320 C1 2007.06.30
F
(300 MHz) (CDCl3) 3.33 (m, 2H), 3.72-3.99
., 12H, (δ = 3.84, s δ = 3.88, s)), 6.02 (d,
113-115 J = 5.6 Hz, 1H), 6.93 (d, J = 8.6 Hz, 1H), 7.02
(m, 1H), 7.28 (m, 1H), 7.38 (m, 1H), 8.05 (d,
J = 5.6 Hz, 1H).
(300 MHz) (CDCl3) 3.51 (m, 2H), 3.75-4.33
., 12 H, (δ = 3.85, s and δ = 4.09, s)), 6.28
163-164 (d, J = 7.0 Hz, 1H), 6.95 (d, J = 8.3 Hz, 1H),
7.02 (m, 1H), 7.25 (m, 1H), 7.40 (m, 1H), 8.10
(d, J = 8.3 Hz, 1H).
54
3
-
-
S
125-129
O
55
57
3
3
-
O
-
S
-
O
HCI
D
HCl
D
HCl
D
21
58
3
59
3
-
-
F3 C
F3 C
-
O
O
HCl
D
F3 C
60
3
-
-
O
F3 C
61
3
-
O
HCI
D
149-151
151-154
136-138
(300 MHz) (CDCl3) 3.45 (m, 2H), 3.74-3.99
., 9 , (δ = 3.88, s)), 6.04 (d, J = 5.6 Hz,
123-126
1H), 7.56 and 7.71 (system AB, J = 8,0 Hz,
4H), 8.06 (d, J = 5.6 Hz, 1H).
(300 MHz) (CDCl3) 3.57-4.29 ( ., 11 ,
(δ = 4.08, s)), 7.31 (d, J = 6.7 Hz, 1H), 7.55
140-143
and 7.73 (system AB, J = 8.2 Hz, 4H), 8.11 (d,
J = 6.7 Hz, 1H).
(300 MHz) (CDCl3) 3.49 (m, 2H), 3.73-4.00
., 9 , (δ = 3.88, s)), 6.04 (d, J = 5.6 Hz,
oil
1H), 7.53-7.78 ( ., 4 ), 8.06 (d, J = 5.6 Hz,
1H).
(300 MHz) (CDCl3) 3.55-4.40 ( ., 11 ,
(δ = 4.08, s)), 6.32 (d, J = 7.1 Hz, 1H), 7.60
177-179
(m, 2H), 7.72 (m, 2H), 8.11 (d, J = 7.1 Hz,
1H).
(KBr) 1589, 1561,
1470, 1233.
(KBr) 2800-2200
(broad), 1644, 1609,
1491, 1241, 1217.
(KBr) 2800-2200
(broad), 1637, 1604,
1494, 1212.
(KBr) 2800-2200
(broad), 1643, 1637,
1629, 1611, 1488,
1265.
(KBr) 1645, 1593,
1561, 1433, 1256.
(KBr) 2800-2200
(broad), 1640, 1611,
1491, 1327, 1264.
(film) 1643, 1587,
1567, 1332.
(KBr) 2800-2200
(broad), 1637, 1611,
1490, 1333, 1322,
1264.
BY 9320 C1 2007.06.30
56
3
(300 MHz) (CDCl3) 3.68 (m, 2H), 3.82 (m,
2H), 3.88 (s, 3H), 4.07 (m, 2H), 4.48 (m, 2H),
6.06 (d, J = 5.7 Hz, 1H), 7.29-7.41 ( ., 5H),
8.08 (d, J = 5.7 Hz, 1H).
(300 MHz) (CDCl3) 1.84-2.14 ( ., 2H), 2.30
(m, 1H), 3.41-4.53 ( ., 13H, (δ = 4.06, s)),
4.57 (t, J = 6.3 Hz, 1H), 6.29 (d, J = 6.9 Hz,
1H), 8.12 (d, J = 6.9 Hz, 1H).
(300 MHz) (CDCl3) 3.87 (broad, 2H), 4.09 (s,
3H), 4.22 (broad, 4H), 4.53 (broad, 2H), 6.33
(d, J = 6.2 Hz, 1H), 7.27-7.44 ( ., 5H), 8.12
(d, J = 6.2 Hz, 1H).
(300 MHz) (CDCl3) 3.61-4.37 ( ., 11 ,
(δ = 4.08, s)), 6.30 (d, J = 7.2 Hz, 1H), 7.43
(m, 5H), 8.10 (d, J = 7.2 Hz, 1H).
CF3
62
3
-
-
O
93-97
CF3
64
3
3
-
O
-
O
HCl
D
-
155-158
102-105
N
22
65
3
-
O
2HCl
D
148-151
N
66
67
3
-
3
-
3
-
O
N
O
N
N
68
N
O
-
2HCl
-
149-152
D
157-161
B
127-131
(KBr) 1641, 1587,
1569, 1436, 1341,
1314, 1251
(KBr) 2800-2200
(banda ancha), 1645,
1604, 1486, 1317,
1126.
(KBr) 1623, 1589,
1566, 1439.
(KBr) 2800-2200
(broad), 1641, 1609,
1493, 1442, 1268.
(KBr) 1638, 1589,
1561, 1340.
(KBr) 2800-2200
(broad), 1634, 1610,
1488, 1415, 1356,
1287, 1265.
(KBr) 1691, 1599,
1556, 1430, 1418,
1241, 988.
BY 9320 C1 2007.06.30
63
(300 MHz) (CDCl3) 3.24 (m, 2H), 3.75 (m,
2H), 3.82-3.96 ( ., 7 , (δ = 3.87, s)), 6.03 (d,
J = 5.6 Hz, 1H), 7.36 (d, J = 7.3 Hz, 1H),
7.54 (t, J = 7.6 Hz, 1H), 7.62 (t, J = 7.6 Hz, 1H),
7.73 (d, J = 7.3 Hz, 1H), 8.05 (d, J = 5.6 Hz, 1H).
(300 MHz) (CDCl3) 3.42 (broad singlet, 2H),
3.70-4.43 ( ., 9 , (δ = 4.07, s)), 6.30 (d.
J = 7.1 Hz, 1H), 7.33 (d, J = 7.2 Hz, 1H),
7.60 (m, 2H), 7.74 (d, J = 7.2 Hz, 1H),
8.08 (d,J = 7.1 Hz, 1H).
(300 MHz) (CDCl3) 3.51 (m, 2H), 3.69-4.00
., 9 , (δ = 3.88, s)), 6.04 (d, J = 5.6 Hz,
1H), 7.39 (dd, J = 7.7 Hz, J' = 5.0 Hz, 1H),
7.79 (d, J = 7.7 Hz, 1H), 8.06 (d, J = 5.6 Hz, 1H),
8.70 (m, 2H).
(300 MHz) (DMSO-d6) 3.66-4.42 ( ., 11H,
(δ = 3.92, s)), 6.32 (d, J = 6.3 Hz, 1H), 7.78
(dd, J = 7.9 Hz, J' = 5.4 Hz, 1H), 8.14 (d,
J = 6.3 Hz, 1H), 8.22 (d, J = 7.9 Hz, 1H), 8.81
(d, J = 5.4 Hz, 1H), 8.85 (s, 1H).
(300 MHz) (CDCl3) 3.43 (m, 2H), 3.75-3.98
., 9H, (δ = 3.88, s)), 6.05 (d, J = 5.7 Hz,
1H), 7.32 (m, 2H), 8.06 (d, J = 5.7 Hz, 1H),
8.73 (m, 2H).
(300 MHz) (DMSO-d6) 3.42 (m, 2H), 3.734.05 ( ., 9H, (δ = 3.94, s)), 6.37 (d, J = 6.5
Hz, 1H), 7.98 (d, J = 5.5 Hz, 2H), 8.14 (d,
J = 6.5 Hz, 1H), 8.96 (d, J = 5.5 Hz, 1H).
(300 MHz) (CDCl3) 3.68 (m, 4H), 3.89 (s, 3H),
3.92 (m, 4H), 6.06 (d, J = 5.7 Hz, 1H), 7.12 (s,
1H), 7.24 (s, 1H), 7.91 (s, 1H), 8.07 (d,
J = 5.7Hz, 1H).
N
69
70
3
-
N
CF3-
O
HCl
D
-
O
160-163
125-126
71
CF3-
O
HCl
D
149-154
23
N
72
3
-
O
-
108-111
N
73
3
-
O
2HCl
D
157-161
N
S
74
2
5
-
O
-
97-99
(KBr) 2800-2200
(broad), 1733, 1639,
1612, 1490, 1416.
(KBr) 1631, 1593,
1502, 1434, 1331,
1257, 1158.
(KBr) 2800-2200
(broad), 1634, 1595,
1524, 1435, 1338,
1273, 1186, 981.
(KBr) 1623, 1595,
1585, 1565, 1473,
1263.
(KBr) 2800-2200
(broad), 1650, 1606,
1495, 1444, 1265.
(KBr) 1605, 1583,
1560, 1449, 1438,
1258, 1237.
BY 9320 C1 2007.06.30
N
(300 MHz) (DMSO-d6) 3.68 (m, 4H), 3.95 (s,
3H), 3.98 (m, 4H), 6.35 (d, J = 6.0 Hz, 1H),
7.82 (s, 1H), 8.05 (s, 1H), 8.17 (d, J = 6,0 Hz,
1H), 9.54 (s, 1H).
(300 MHz) (CDCl3) 3.41-4.15 ( ., 8H), 6.84
(d, J = 4.8 Hz, 1H), 7.40 (ddd, J = 7.9 Hz,
J' = 4.8 Hz, J" = 0.9 Hz, 1H), 7.80 (ddd, J = 7.9
Hz, J' = 2.1 Hz, J" = 1.8 Hz, 1H), 8.53 (d,
J = 4.8 Hz, 1H), 8.71 (m, 2H).
(300 MHz) (DMSO-d6, TF ) 3.46 (m, 2 ),
3.67-4.03 ( ., 6 ), 7.03 (d, J = 4.8 Hz, 1H),
8.05 (dd, J = 8.0 Hz, J' = 5.6 Hz, 1H), 8.56 (d,
J = 8.0 Hz, 1H), 8.68 (d, J = 4.8 Hz, 1H), 8.95
(d, J = 5.6 Hz, 1H), 9.04 (s, 1H).
(300 MHz) (CDCl3) 3.69 (m, 2H), 3.81-4.02
., 9 , (δ = 3.88, s)), 6.02 (d, J = 5.7 Hz,
1H), 7.37 (m, 1H), 7.70 (d, J = 8.0 Hz, 1H),
7.82 (dt, J = 8.0 Hz, J' = 1.7 Hz, 1H), 8.06 (d,
J = 5.7 Hz, 1H), 8.61 (d, J = 5.1 Hz, 1H).
(300 MHz) (DMSO-d6, TFA) 3.67 (broad),
3.79-4.07 ( ., 9H, (δ = 3.99, s)), 6.48 (d,
J = 6.5 Hz, 1H), 7.63 (m, 1H), 7.78 (m, 1H),
8.09 (m, 1H), 8.19 (d, J = 6.5 Hz, 1H), 8.68 (d,
J = 4.6 Hz, 1H).
(300 MHz) (CDCl3) 1.37 (t, J = 7.1 Hz, 3H),
3.77-3.93 ( ., 8 ), 4.33 (q, J = 7.1 Hz, 2H),
6.01 (d, J = 5.6 Hz, 1H), 7.07 (m, 1H), 7.33 (d,
J = 3.4 Hz, 1H), 7.47 (d, J = 4.9 Hz, 1H), 8.06
(d, J = 5.6 Hz, 1H).
S
75
2
5
-
O
HCl
D
S
2
5
-
-
O
Cl
77
S
2
5
-
O
HCl
D
24
Cl
CF3
78
2
5
-
-
O
CF3
79
2
5
-
O
HCl
D
CH2
80
3
-
O
-
(KBr) 2800-2200
(broad), 1609, 1434,
1257, 994.
(KBr) 1625, 1558,
1436, 1255.
(KBr) 2800-2200
(broad) 1639, 1617,
1604, 1460, 1440,
1292, 1260, 1203.
(KBr) 1624, 1582,
1437, 1258.
(KBr) 2800-2200
(broad), 1640, 1602,
1437, 1320, 1259
(KBr) 1621, 1598,
1559, 1430, 1263.
BY 9320 C1 2007.06.30
76
(300 MHz) (CDCl3) 1.45 (t, J = 7.1 Hz, 3H),
3.80-4.40 ( ., ( ), 4.50 (q, J = 7.1 Hz, 2H),
138-139 6.27 (d, J = 6.9 Hz, 1H), 7.08 (dd, J = 4.9 Hz,
J' = 3.8 Hz, 1H), 7.33 (d, J = 3.8 Hz, 1H), 7.50
(d, J = 4.9 Hz, 1H), 8.10 (d, J = 6.9 Hz, 1H).
(300 MHz) (CDCl3) 1.36 (t, J = 7.1 Hz, 3H),
3.45-3.97 ( ., 8 ). 4.32 (q, J = 7.1 Hz, 2H),
91-94 6.01 (d, J = 5.6 Hz, 1H), 6.93 (d, J = 5.2 Hz,
1H), 7.40 (d, J = 5.2 Hz, 1H), 8.06 (d, J = 5.6
Hz, 1H).
(300 MHz) (CDCl3) 1.46 (t, J = 7.0 Hz, 3 ),
3.81 (broad, 4H), 3.93-4.42 ( ., 4H), 4.51 (q,
167-169 J = 7.0 Hz, 2H), 6.28 (d, J = 6.9 Hz, 1H), 6.95
(d, J = 5.3 Hz, 1H), 7.44 (d, J = 5.3 Hz, 1H),
8.10 (d, J = 6.9 Hz, 1H).
(300 MHz) (CDCl3) 1.36 (t, J = 7.1 Hz, 3H),
3.23 (m, 2H), 3.73 (m, 2H), 3.88 ( ., 4H),
99-101 4.31 (q, J = 7.1 Hz, 2H), 6.00 (d, J = 5.6 Hz, 1H),
7.36 (d, J = 7.2 Hz, 1H), 7.54 (m, 1H), 7.62 (m,
1H), 7.73 (m, 1H), 8.05 (d, J = 5.6 Hz, 1H).
(300 MHz) (CDCl3) 1.45 (t, J = 7.1 Hz, 3H),
3.42 (broad, 2H), 3.68-4.41 ( ., 6H), 4.50 (m,
146-148 2H), 6.27 (d, J = 6.7 Hz, 1H), 7.33 (d, J = 7.1
Hz, 1H), 7.61 (m, 2H), 7.74 (d, J = 7.9 Hz,
1H), 8.07 (d, J = 6.7 Hz, 1H).
(300 MHz) (CDCl3) 2.33 (s, 3H), 3.30 (broad,
2H), 3.74 (broad, 2H), 3.83-3.98 ( ., 7H,
70-73 (δ = 3.87, s)), 6.03 (d, J = 5.5 Hz, 1H), 7.157.34 (m, 4H), 8.05 (d, J = 5.5 Hz, 1H).
(KBr) 2800-2200
(broad), 1643, 1630,
1610, 1491, 1415,
1263.
(KBr) 1632, 1583.
1557,1450, 1236.
81
3
82
3 )2
83
3 )2
-
O
-
-
HCl
-
O
F
O
F
84
D
HCl
(300 MHz) (CDCl3) 1.42 (d, J = 6.1 Hz, 6H),
3.66-4.44 ( ., 8H), 5.39 (h, J = 6.1 Hz, 1H),
148-150 6.23 (d, J = 5.7 Hz, 1H), 6.95 (d, J = 5.3 Hz, 1H),
7.44 (d, J = 5.3 Hz, 1H), 8.08 (d, J = 5.7 Hz, 1H).
(KBr) 2800-2200
(broad) 1644, 1612,
1462, 1446, 1313,
1282, 1250.
151-153
112-115
D
163-166
CF3
25
3 )2
-
-
O
-
CF3
85
3 )2
-
O
HCl
D
159-161
S
86
3 )2
-
-
O
68-70
Cl
S
87
3 )2
-
O
Cl
HCl
D
(KBr) 2800-2200
(broad) 1636, 1608,
1458, 1432, 1259.
(KBr) 1651, 1581,
1563, 1317.
(KBr) 2800-2200
(broad), 1640, 1604,
1473, 1317, 1122.
(KBr) 1631, 1583,
1557, 1445.
BY 9320 C1 2007.06.30
(300 MHz) (CDCl3) 2.30 (s, 3H), 3.48 (broad,
2H), 3.90-4.35 ( ., 9H, (δ = 4.08, s)), 6.29 (d,
J = 6.0 Hz, 1H), 7.13-7.32 ( ., 4H), 8.10 (d,
J = 6.0 Hz, 1H).
(300 MHz) (CDCl3) 1.31 (d, J = 6.0 Hz, 6H),
3.40-4.00 ( ., 8H). 5.24 (h, J = 6.0 Hz, 1H),
5.96 (d, J = 5.7 Hz, 1H), 7.13 (t, J = 7.8 Hz,
2H), 7.46 (m, J = 8.8 Hz, J' = 5.4 Hz, 2H), 8.03
(d, J = 5.7 Hz, 1H).
(300 MHz) (CDCl3) 1.41 (d, J = 6.0 Hz, 6H),
3.65-4.40 ( ., 8H), 5.39 (m, 1H), 6.22 (d,
J = 6.9 Hz, 1H), 7.13 (m, 2H), 7.43 (m, 2H),
8.07 (d, J = 6.9 Hz, 1H).
(300 MHz) (CDCl3) 1.29 (d, J = 6.0 Hz, 6H),
3.24 (m, 2H), 3.72 (m, 2H), 3.89 (m, 4H), 5.24
(h, J = 6.0 Hz, 1H), 5.97 (d, J = 5.7 Hz, 1H),
7.36 (d, J = 7.2 Hz, 1H), 7.58 (m, 2H), 7.73 (d,
J = 7.8 Hz, 1H), 8.04 (d, J = 5.7 Hz, 1H).
(300 MHz) (CDCl3) 1.42 (d, J = 5.6 Hz, 6H),
3.43 (broad, 2H), 3.67-4.44 ( ., 6H), 5.40 (m,
1H), 6.22 (d, J = 6.8 Hz, 1H), 7.33 (d, J = 6.9
Hz, 1H), 7.61 (m, 2H), 7.75 (d, J = 7.5 Hz,
1H), 8.05 (d, J = 6.9 Hz, 1H).
(300 MHz) (CDCl3) 1.33 (d, J = 6.1 Hz, 6H),
3.40-4.07 ( ., 8H), 5.26 (h, J = 6.1 Hz, 1H),
5.97 (d, J = 5.7 Hz, 1H), 6.93 (d, J = 5.3 Hz, 1H),
7.39 (d, J = 5.3 Hz, 1H), 8.05 (d, J = 5,7 Hz, 1H).
CH2
88
3
89
2
5
-
-
-
O
O
HCl
109-111
D
-
F
121-124
136-138
91
26
2
5
-
HCl
F
D
155-157
S
92
3
-
O
-
106-108
N
93
3
-
-
145-147
NH2
94
3
-
2HCl
NH2
D
(KBr) 1629, 1591,
1556, 1339, 1239, 992.
(KBr) 2800-2200
(broad), 1632, 1604,
1487, 1431, 1212.
(KBr) 1616, 1590,
1557, 1432.
(KBr) 2800-2200
(broad), 1636, 1606,
1458, 1436, 1258.
(KBr) 1596, 1565,
1496, 1442, 1257,
1004.
(KBr) 3444, 3323,
1617, 1586, 1566,
1498, 1467, 1260.
(300 MHz) (DMSO-d3) 3.61 (broad, 4H), 3.94 (KBr) 3700-2200
(s, 7H), 6.37 (d, J = 6.5 Hz, 1H), 7.10 (t,
(broad), 1614, 1493,
155-157 J = 7.5 Hz, 1H), 7.20 (d, J = 7.5 Hz, 1H), 7.32 1439, 1257.
(d, J = 7.5 Hz, 1H), 7.38 (t, J = 7.5 Hz, 1H),
8.14 (d, J = 6.5 Hz, 1H).
BY 9320 C1 2007.06.30
90
3
-
(300 MHz) (CDCl3) 1.28 (m, 3H), 1.46-1.89
., 7H), 2.50 (tt, J = 11.2 Hz, J' = 3.3 Hz,
1H), 3.56 (m, 2H), 3.69 (m, 2H), 3.81 (m, 4H),
3.89 (s, 3H), 6.02 (d, J = 5.5 Hz, 1H), 8.06 (d,
J = 5.5 Hz, 1H).
(300 MHz) (CDCl3) 1.27 (m, 3H), 1.53 (m,
), 1.75 ( ., 5 ), 2.47 (m, 1H), 3.75 (broad
singlet, 4 ), 3.92 (m, 2 ), 4.07 (s, 3 ), 4.29
(m, 2 ), 6.30 (d, J = 7.0 Hz, 1 ), 8.11 (d,
J = 7.0 Hz, 1H).
(300 MHz) (CDCl3) 1.37 (t, J = 7.0 Hz, 3H),
3.38-4.00 ( ., 8H), 4.32 (q, J = 7.0 Hz, 2H),
6.01 (d, J = 5.7 Hz, 1H), 7.12 (t, J = 8.5 Hz,
2H), 7.45 (m, 2H), 8.06 (d, J = 5.7 Hz, 1H).
(300 MHz) (CDCl3) 1.46 (t, J = 7.0 Hz, 3H),
3.67-4.38 ( ., 8H), 4.51 (q, J = 7.0 Hz, 2H),
6.28 (d, J = 6.8 Hz, 1H), 7.14 (t, J = 8.8 Hz,
2H), 7.45 (m, 2H), 8.11 (d, J = 6.8 Hz, 1H).
(300 MHz) (CDCl3) 3.85-3.99 ( ., 9H,
(δ = 3.90, s)), 4.50 (m, 2H), 6.03 (d, J = 5.7
Hz, 1H), 7.56 (d, J = 3.2 Hz, 1H), 7.91 (d,
J = 3.2 Hz, 1H), 8.07 (d, J = 5.7 Hz, 1H)
(300 MHz) (CDCl3) 3.70 (broad, 4H), 3.833.90 ( ., 7H, (δ = 3.88, s)), 4.35 (s, 2H), 6.03
(d, J = 5.6 Hz, 1H), 6.74 (m, 2H), 7.11 (m,
1H), 8.06 (d, J = 5.6 Hz, 1H).
S
95
3
-
-
O
F
S
96
3
-
HCl
D
97
3
-
(KBr) 1626, 1586,
1469, 1443.
(KBr) 2800-2200
(broad), 1618, 1482,
1413, 1262, 995.
(300 MHz) (CDCl3) 3.25 (m, 2H), 3.65-3.99
(KBr) 3600-2500
(broad), 1711, 1583,
., 9H, (δ = 3.86, s)), 6.02 (d, J = 5.8 Hz,
1444, 1342, 1266.
1H),
7.30
(d,
J
=
7.6
Hz,
1H),
7.45
(t,
J
=
7.6
186-188
Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 8.06 (m, 2H).
OH
27
O
98
3
-
O
(300 MHz) (CDCl3) 2.27 (s, 3H), 3.38 (m, 2H), (KBr) 1764, 1637,
1566, 1429, 1338,
3.74-3.94 ( ., 9H, (δ = 3,87, s)), 6.03 (d,
139-142 J = 5.7 Hz, 1H), 7.18 (d, J = 8.2 Hz, 1H), 7.32 1259, 1194.
(m, 2H), 7.44 (m, 1H), 8.05 (d, J = 5.7 Hz, 1H).
-
O
O
CH2
99
3
-
-
B
OH
100
3
-
D Na
D
D
(300 MHz) (CDCl3) 3.80 (m, 4H), 3.86-3.95
., 7H, (δ = 3.89)), 6.04 (d, J = 5.7 Hz, 1H),
186-188 6.87 (t, J = 7.5 Hz, 1H), 7.03 (d, J = 8.1 Hz, 1H),
7.28 (m, 1H), 7.35 (m, 1H), 8.06 (d, J = 5.7 Hz,
1H).
(300 MHz) (DMSO-d6) 3.06 (m, 2H), 3.383.72 ( ., 4H), 3.79 (s, 3H), 3.92 (m, 2H), 6.04
(d, J = 5.4 Hz, 1H), 7.02 (m, 1H), 7.27 (m,
2H), 7.79 (m, 1H), 8.06 (d, J = 5,4 Hz, 1H).
(KBr) 3500-2500
(broad), 1566, 1443,
1335, 1229.
(KBr) 1624, 1588,
1563, 1382.
BY 9320 C1 2007.06.30
F
(300 MHz) (CDCl3) 3.73 (broad, 4H), 3.863.99 ( ., 7H, (δ = 3.89, s)), 6.03 (d, J = 5.7
Hz, 1H), 6.78 (d, J = 5.4 Hz, 1H), 7.37 (dd,
oil
J = 5.4 Hz, J' = 3.7 Hz, 1H), 8.06 (d, J = 5.7 Hz,
1H).
(300 MHz) (CDCl3) 3.86 (broad singlet, 4 ),
4.08 (s, 5H), 4.23-4.45 (m, 2H), 6.31 (d,
156-157 J = 6.9 Hz, 1H), 6.80 (d, J = 5.5 Hz, 1H), 7.41
(dd, J = 5.5 Hz, J' = 3.7 Hz, 1H), 8.12 (d,
J = 6.9 Hz, 1H).
101
3
-
O
HCl
D
OH
3
-
HCl
D
N
103
3
-
NO3H
28
O
D
CH2
S
104
3
-
O
NO3H
Cl
105
3
2
-
N
D
(KBr) 3500-2500
(broad), 1622, 1493,
1361, 1289, 1211.
(KBr) 3500-2500
(broad), 1616, 1486,
1413, 1311, 1212.
(KBr) 3500-2500
(broad), 1646, 1485,
1281, 1000, 750.
(300 MHz) (CDCl3) 3.81 (broad, 4H), 4.02
(KBr) 3500-2500
(broad, 4H), 4.08 (s, 3H), 6.33 (d, J = 7.0 Hz, (broad), 1643, 1486,
129-131 1H), 6.95 (d, J = 5.0 Hz, 1H), 8.25 (d, J = 7.0 Hz, 1411, 1258, 077.
1H).
87-90
(300 MHz) (CDCl3) 1.36 (t, J = 7.0 Hz, 3H),
(KBr) 1634, 1578,
3.68 (m, 2H), 3.78-3.99 ( ., 6 ),
1557, 1447, 1237,
4.33 (q, J = 7.0 Hz, 2H), 6.00 (d, J = 5.6 Hz, 1H), 1000.
7.69 (d, J = 7.9 Hz, 1H), 7.82 (dt, J = 7.9 Hz,
J' = 1.5 Hz, 1H), 8.05 (d, J = 5.6 Hz, 1H), 8.60
(d, J = 4.8 Hz, 1H).
BY 9320 C1 2007.06.30
102
(300 MHz) (DMSO-d6) 3.34 (m, 2H), 3.624.01 ( ., 9H, (δ = 3.93)), 6.36 (d, J = 6.3 Hz,
158-159 1H), 6.84 (t, J = 7.2 Hz, 1H). 6.91 (d, J = 8.1
Hz, 1H), 7.15 (m, 1H), 7.23 (m, 1H), 8.13 (d,
J = 6.3 Hz, 1H).
(300 MHz) (CDCl3) 3.93 (broad s, 4H), 4.004.40 ( ., 7 , (δ = 4.07, s)), 6.29 (d, J = 6.8
Hz, 1H), 7.40 (m, 1H), 7.72 (broad d, J = 7.2
151-153
Hz, 1H), 7.84 (dt, J = 7.6 Hz, J' = 1.7 Hz, 1H),
8.11 (d, J = 6.8 Hz, 1H), 8.59 (d, J = 5.0 Hz,
1H).
(300 MHz) (CDCl3) 3.31-3.64 ( ., 2 ), 3.704.24 ( ., 12 , (δ = 3.85, s) (δ = 4.08, s)), 6.30
137-139 (d, J = 6.9 Hz, 1H), 6.95 (8.2 Hz, 1H), 8.23 (d,
J = 6.9 Hz, 1H).
BY 9320 C1 2007.06.30
,
,
,
,
David Sudgen (J. Pharmacol. Exp. Ther., 1983, 227, 3).
(150
,
)
100
(
).
50 (DE50). . 2,
.
2
,
%
2
4
8
9
10
11
13
15
17
18
22
24
26
30
32
34
55
57
59
61
63
65
67
69
73
81
83
87
89
91
92
94
96
(
100
93
100
97
67
74
89
77
86
56
82
57
69
60
75
73
98
70
100
101
102
103
100
96
97
98
99
100
101
102
81
98
84
97
54
29
)
DE50 (
14,4
8,7
9,7
28,1
11,6
10,5
41,3
8,2
84,2
27,3
75
41,5
74,1
37,2
56,5
7
31
1,6
14
4,5
4
7,7
15
10
9,5
8,3
5,3
10
8
10
8
5,2
3
84,5
)
BY 9320 C1 2007.06.30
,
-
.
.
. 3,
,
(
)
,
.
3
.
(
80
40
80
40
80
40
80
40
80
40
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
80
106
120
80
2
4
15
30
34
57
59
61
65
63
71
73
77
79
81
85
87
89
91
92
96
101
)
( )
15
20
15
30
30
20
10
20
60
30
20
SMART (Letica S.A.)
)
5,3
0,6
7,4
1,3
1,9
1,4
7,9
1,8
1,5
0
11
3,4
1,6
8,6
14,8
5,6
9
10
19
10
8,4
10
4
7
5
6
2
6,2
3,9
0
12
.
Heffneren J. Pharm. Exp. Ther., 1989, 251, 195-112.
.
(
,
T.G.
.
(
1)
5
.
30
BY 9320 C1 2007.06.30
S. IRWING
,
(Gordon Res. Conf. On Medicinal Chem., 1959, p. 133).
80
(1/2, 1, 2, 3, 4
,
,
5
,
,
)
.
.4,
,
.
,
,
.
4
Irwing
= 80
,
]
%
1/2
100
60
100
100
100
100
100
100
100
90
100
100
4
34
57
63
71
73
75
77
79
83
92
:
1
90
70
100
100
100
100
100
100
100
90
100
100
2
10
80
100
90
100
100
100
100
100
90
100
70
3
0
85
80
75
40
0
80
60
65
70
0
0
4
0
40
55
20
10
0
80
0
0
50
0
0
0
40
0
0
0
0
60
0
0
0
0
0
,
,
Segmund E., and coworkers (Proc. Soc. Exp. Biol. Med., 1957, 95:
,
729-731).
,
5
.
.
DE50 (
-
50)
,
4.
,
.
5
.
DE50 (
4
,
84
48
31
,
)
DE50 (
,
120
72
)
BY 9320 C1 2007.06.30
1.
(
):
4
0,1
HCl
5
c.s.
c.s.
3
NaOH
c.s. .
2.
4
0,5
0,5
1,0
100
4,0
4
0,5
0,5
1,0
60
100
4,0
c.s. .
3.
c.s. .
(
)
4
0,5
4,0
0,5
1,0
5,0
5,0
20
100 .
-30
c.s. .
.
220034, .
,
.
, 20.
32
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