S. Bindi et al. / Bioorg. Med. Chem. 18 (2010) 7113–7120
7119
[M+H]+; HRMS (ESI) m/z calcd for C25H26N6O2S + H+ 475.1911,
found 475.1914.
7.38–7.43 (m, 2H), 7.35 (m, 2H), 7.22–7.28 (m, 1H), 7.00 (d,
J = 9.0 Hz, 2H), 4.83–4.96 (m, 1H), 3.19–3.51 (m, 4H), 2.41–2.72 (m,
4H), 2.28 (br s, 3H), 1.70–1.96 (m, 2H), 0.93 (t, J = 7.3 Hz, 3H); LC–
MS (ESI) m/z 503 [M+H]+; HRMS (ESI) m/z calcd for C27H30N6O2S + H+
503.2224, found 503.2221.
5.1.2.6. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thie-
no[3,2-c]pyrazole-5-carboxylic acid (1-phenyl-ethyl)-amide
(23). Yield, 56%; 1H NMR (400 MHz, DMSO-d6) d 12.74 (s, 1H),
10.95 (s, 1H), 8.85 (d, J = 8.2 Hz, 1H), 7.98 (d, J = 9.0 Hz, 2H), 7.82
(s, 1H), 7.39–7.44 (m, 2H), 7.36 (t, J = 7.4 Hz, 2H), 7.25 (m, 1H),
7.00 (d, J = 9.0 Hz, 2H), 5.15 (quin, J = 7.1 Hz, 1H), 3.31 (m, 4H),
2.46 (m, 4H), 2.24 (s, 3H), 1.51 (d, J = 7.1 Hz, 3H); LC–MS (ESI) m/
5.1.2.13. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thie-
no[3,2-c]pyrazole-5-carboxylic acid (1-methyl-1-phenyl-ethyl)-
amide (30). Yield, 30%; 1H NMR (400 MHz, DMSO-d6) d 12.75 (s,
1H), 10.94 (s, 1H), 8.46 (s, 1H), 7.97 (d, J = 9.0 Hz, 2H), 7.88 (s, 1H),
7.38–7.43 (m, 2H), 7.31 (m, 2H), 7.16–7.22 (m, 1H), 7.00 (d,
J = 9.0 Hz, 2H), 3.27–3.36 (m, 4H), 2.45–2.53 (m, 4H), 2.28 (br s,
3H), 1.69 (s, 6H); LC–MS (ESI) m/z 503 [M+H]+; HRMS (ESI) m/z calcd
for C27H30N6O2S + H+ 503.2224, found 503.2228.
z
489 [M+H]+; HRMS (ESI) m/z calcd for C26H28N6O2S + H+
489.2067, found 489.2070.
5.1.2.7. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thie-
no[3,2-c]pyrazole-5-carboxylic acid (1-phenyl-propyl)-amide
(24). Yield, 65%; 1H NMR (400 MHz, DMSO-d6) d 12.74 (s, 1H),
10.95 (s, 1H), 8.77 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 9.0 Hz, 2H), 7.83
(s, 1H), 7.38–7.45 (m, 2H), 7.35 (m, 2H), 7.25 (m, 1H), 7.00 (d,
J = 9.0 Hz, 2H), 4.83–4.94 (m, 1H), 3.34 (m, 4H), 2.47 (m, 4H),
2.25 (s, 3H), 1.72–1.96 (m, 2H), 0.93 (t, J = 7.3 Hz, 3H); LC–MS
(ESI) m/z 503 [M+H]+; HRMS (ESI) m/z calcd for C27H30N6O2S + H+
503.2224, found 503.2226.
5.1.2.14. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thi-
eno[3,2-c]pyrazole-5-carboxylic acid indan-1-ylamide (31). Yield,
56%; 1H NMR (400 MHz, DMSO-d6) d 12.71 (s, 1H), 10.96 (s, 1H),
8.84 (d, J = 8.3 Hz, 1H), 7.99 (d, J = 9.0 Hz, 2H), 7.76 (s, 1H), 7.17–
7.37 (m, 4H), 7.02 (d, J = 9.0 Hz, 2H), 5.54 (q, J = 8.1 Hz, 1H),
3.13–3.54 (m, 4H), 2.81–3.09 (m, 2H), 2.40–2.64 (m, 4H), 2.29 (br
s, 3H), 1.88–2.07 (m, 2H); LC–MS (ESI) m/z 501 [M+H]+; HRMS
(ESI) m/z calcd for C27H28N6O2S + H+ 501.2067, found 501.2064.
5.1.2.8. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thieno
[3,2-c]pyrazole-5-carboxylic acid benzhydryl-amide (25). Yield,
62%; 1H NMR (400 MHz, DMSO-d6) d 12.77 (s, 1H), 10.97 (s, 1H),
9.31 (d, J = 8.7 Hz, 1H), 7.99 (d, J = 9.0 Hz, 2H), 7.96 (s, 1H), 7.25–
7.43 (m, 10H), 7.01 (d, J = 9.0 Hz, 2H), 6.40 (d, J = 8.7 Hz, 1H), 2.45–
3.53 (m, 8H), 2.32 (br s, 3H); LC–MS (ESI) m/z 551 [M+H]+; HRMS
(ESI) m/z calcd for C31H30N6O2S + H+ 551.2224, found 551.2223.
5.1.2.15. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thi-
eno[3,2-c]pyrazole-5-carboxylic acid (1,2,3,4-tetrahydro-naph-
thalen-1-yl)-amide (32). Yield, 61%; 1H NMR (400 MHz, DMSO-d6)
d 12.70 (s, 1H), 10.95 (s, 1H), 8.84 (d, J = 8.7 Hz, 1H), 7.99 (d, J = 9.0 Hz,
2H), 7.77 (s, 1H), 7.09–7.29 (m, 4H), 7.02 (d, J = 9.0 Hz, 2H), 5.14–5.30
(m, 1H), 3.14–3.53 (m, 4H), 2.71–2.91 (m, 2H), 2.40-2.63 (m, 4H), 2.28
(br s, 3H), 1.65–2.08 (m, 4H); LC–MS (ESI) m/z 515 [M+H]+; HRMS
(ESI) m/z calcd for C28H30N6O2S + H+ 515.2224, found 515.2226.
5.1.2.9. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thie-
no[3,2-c]pyrazole-5-carboxylic acid (R)-1-phenyl-ethyl)-amide
(26). Yield, 75%; 1H NMR (400 MHz, DMSO-d6) d 12.75 (s, 1H),
10.96 (s, 1H), 8.85 (d, J = 8.2 Hz, 1H), 7.98 (d, J = 9.0 Hz, 2H), 7.82
(s, 1H), 7.39–7.44 (m, 2H), 7.35 (m, 2H), 7.25 (m, 1H), 7.01 (d,
J = 9.0 Hz, 2H), 7.40 (quin, J = 7.4 Hz, 1H), 2.99–3.55 (m, 4H),
2.40–2.82 (m, 4H), 2.32 (br s, 3H), 1.51 (d, J = 7.1 Hz, 3H); LC–MS
(ESI) m/z 489 [M+H]+; HRMS (ESI) m/z calcd for C26H28N6O2S + H+
489.2067, found 489.2064.
5.1.2.16. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thi-
eno[3,2-c ]pyrazole-5-carboxylic acid ((S)-1-phenyl-2-pyrroli-
din-1-yl-ethyl)-amide (33). Yield, 40%; 1H NMR (400 MHz,
DMSO-d6) d 12.76 (br s, 1H), 10.97 (s, 1H), 8.84 (br s, 1H), 7.98
(d, J = 9.1 Hz, 2H), 7.83 (s, 1H), 7.42–7.49 (m, 2H), 7.22–7.40 (m,
3H), 7.00 (d, J = 9.1 Hz, 2H), 5.20 (br s, 1H), 3.14–3.53 (m, 4H),
3.5–2.2 (m, 6H), 2.40–2.63 (m, 4H), 2.26 (s, 3H), 1.73 (br s, 4H);
LC–MS (ESI) m/z 558 [M+H]+; HRMS (ESI) m/z calcd for
5.1.2.10. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thi-
eno[3,2-c]pyrazole-5-carboxylic acid ((S)-1-phenyl-ethyl)-amide
(27). Yield, 70%; 1H NMR (400 MHz, DMSO-d6) d 12.73 (s, 1H),
10.95 (s, 1H), 8.83 (d, J = 8.0 Hz, 1H), 7.97 (d, J = 9.0 Hz, 2H), 7.81
(s, 1H), 7.37–7.42 (m, 2H), 7.34 (m, 2H), 7.20–7.27 (m, 1H), 7.00
(d, J = 9.0 Hz, 2H), 5.14 (quin, J = 7.3 Hz, 1H), 3.16–3.45 (m, 4H),
2.55 (br s, 4H), 2.31 (br s, 3H), 1.49 (d, J = 7.1 Hz, 3H); LC–MS
(ESI) m/z 489 [M+H]+; HRMS (ESI) m/z calcd for C31H30N6O2S + H+
489.2067, found 489.2063.
C
30H35N7O2S + H+ 558.2646, found 558.2650.
5.1.2.17. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thi-
eno[3,2-c]pyrazole-5-carboxylic acid ((S)-2-morpholin-4-yl-1-
phenyl-ethyl)-amide (34). Yield, 42%; 1H NMR (400 MHz,
DMSO-d6) d 12.75 (s, 1H), 10.96 (s, 1H), 8.78 (d, J = 8.3 Hz, 1H),
7.98 (d, J = 9.0 Hz, 2H), 7.81 (s, 1H), 7.41–7.46 (m, 2H), 7.36 (m,
2H), 7.23–7.29 (m, 1H), 7.00 (d, J = 9.0 Hz, 2H), 5.15–5.32 (m,
1H), 3.47–3.65 (m, 4H), 3.15–3.45 (m, 4H), 2.34–2.91 (m, 10H),
2.27 (s, 3H); LC–MS (ESI) m/z 574 [M+H]+; HRMS (ESI) m/z calcd
for C30H35N7O3S + H+ 574.2595, found 574.2599.
5.1.2.11. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thi-
eno[3,2-c]pyrazole-5-carboxylic acid ((R)-1-phenyl-propyl)-amide
(28). Yield, 55%; 1H NMR (400 MHz, DMSO-d6) d 12.75 (s, 1H),
10.95 (s, 1H), 8.77 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 9.0 Hz, 2H), 7.83
(s, 1H), 7.39–7.44 (m, 2H), 7.35 (m, 2H), 7.21–7.28 (m, 1H), 7.00
(d, J = 9.0 Hz, 2H), 4.82–4.95 (m, 1H), 3.23–3.46 (m, 4H), 2.44–
2.58 (m, 4H), 2.28 (br s, 3H), 1.73–1.95 (m, 2H), 0.93 (t,
J = 7.32 Hz, 3H); LC–MS (ESI) m/z 503 [M+H]+; HRMS (ESI) m/z calcd
for C27H30N6O2S + H+ 503.2224, found 503.2227.
By employment of the above-described procedure, starting
from 12b and using different amines, compounds 35–37 and 39
were prepared.
5.1.2.18.
3-(4-Morpholin-4-yl-benzoylamino)-1H-thieno[3,2-
c]pyrazole-5-carboxylic acid benzylamide (35). Yield, 44%; 1H
NMR (400 MHz, DMSO-d6) d 12.73 (s, 1H), 10.98 (s, 1H), 9.09
(t, J = 6.0 Hz, 1H), 8.00 (d, J = 9.0 Hz, 2H), 7.72 (s, 1H), 7.22–7.42
(m, 5H), 7.02 (d, J = 9.0 Hz, 2H), 4.49 (d, J = 6.0 Hz, 2H), 3.71–3.80
(m, 4H), 3.18–3.56 (m, 4H); LC–MS (ESI) m/z 462 [M+H]+; HRMS
(ESI) m/z calcd for C24H23N5O3S + H+ 462.1594, found 462.1593.
5.1.2.12. 3-[4-(4-Methyl-piperazin-1-yl)-benzoylamino]-1H-thie-
no[3,2-c]pyrazole-5-carboxylic acid ((S)-1-phenyl-propyl)-amide
(29). Yield, 57%; 1H NMR (400 MHz, DMSO-d6) d 12.75 (s, 1H), 10.95
(s, 1H), 8.77 (d, J = 8.4 Hz, 1H), 7.98 (d, J = 9.0 Hz, 2H), 7.83 (s, 1H),