1050 Journal of Medicinal Chemistry, 2011, Vol. 54, No. 4
Marugan et al.
(t, J=4.4 Hz, 1H), 3.82 (br s, 4H), 3.20 (br s, 4H). MS (ESI) m/z
471 [C22H19ClN4O2S2]þ.
1H), 3.91 (t, J=4.8 Hz, 4H), 3.47 (t, J=4.4 Hz, 4H). MS (ESI)
m/z 455 [C22H19FN4O2S2 þ H]þ.
4-(4-(2-Methylphenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-yl)-
quinazoline (26ab). Yield 29%. 1H NMR (400 MHz, CDCl3) δ
8.02 (br s, 1H), 7.97-7.90 (m, 2H), 7.79 (d, J=8.0 Hz, 1H), 7.72
(t, J=6.0 Hz, 1H), 7.51-7.45 (m, 2H), 7.42-7.34 (m, 3H), 7.15
(t, J=4.0 Hz, 1H), 3.87 (t, J=6.0 Hz, 4H), 3.45 (t, J=6.0 Hz,
4H), 2.69 (s, 3H). MS (ESI) m/z 451 [C23H22N4O2S2 þ H]þ.
4-(4-(3-Methylphenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-yl)-
quinazoline (26ac). Yield 29%. 1H NMR (400 MHz, CDCl3) δ
8.00 (d, J=2.8 Hz, 1H), 7.90 (d, J=8.4 Hz, 1H), 7.75-7.69 (m,
2H), 7.61 (s, 2H), 7.46-7.16 (m, 4H), 7.15 (t, J = 4.4 Hz, 1H),
3.92 (t, J=4.4 Hz, 4H), 3.28 (t, J=4.8 Hz, 4H), 2.44 (s, 3H). MS
(ESI) m/z 451 [C23H22N4O2S2 þ H]þ.
4-(4-(3-Fluorophenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-yl)-
quinazoline (26ao). Yield 70%. H NMR (400 MHz, CDCl3)
1
δ 8.00 (d, J =3.2 Hz, 1H), 7.90 (d, J =8.0 Hz, 1H), 7.75-7.69
(m, 2H), 7.61-7.51 (m, 3H), 7.46 (d, J=4.8 Hz, 1H), 7.40-7.27
(m, 2H), 7.15 (t, J=4.0 Hz, 1H), 3.91 (t, J=4.4 Hz, 4H), 3.30
(t, J=4.4 Hz, 4H). MS (ESI) m/z 455 [C22H19FN4O2S2 þ H]þ.
4-(4-(4-Fluorophenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-yl)-
1
quinazoline (26ap). Yield 67%. H NMR (400 MHz, CDCl3)
δ 8.01 (d, J =4.0 Hz, 1H), 7.90 (d, J =8.0 Hz, 1H), 7.84-7.81
(m, 2H), 7.75-7.69 (m, 2H), 7.46 (t, J=4.0 Hz, 1H), 7.38 (t, J=
8.0 Hz, 1H), 7.27-7.22 (m, 2H), 7.15 (t, J = 4.0 Hz, 1H), 3.91
(t, J=4.0 Hz, 4H), 3.27 (t, J=4.0 Hz, 4H). MS (ESI) m/z 455
[C22H19FN4O2S2 þ H]þ.
4-(4-(4-Methylphenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-yl)-
quinazoline (26ad). Yield 70%. 1H NMR (400 MHz, CDCl3) δ
8.00 (d, J=4.0 Hz, 1H), 7.88 (d, J=8.0 Hz, 1H), 7.74-7.67 (m,
4H), 7.45 (d, J=4.8 Hz, 1H), 7.39-7.33 (m, 3H), 7.15 (t, J=4.0
Hz), 3.91 (t, J = 8.0 Hz, 4H), 3.25 (t, J = 8.0 Hz, 4H), 2.41 (s,
3H). MS (ESI) m/z 451 [C23H22N4O2S2 þ H]þ.
4-(4-(2,4-Difluorophenylsulfonyl)piperazin-1-yl)-2-(thiophen-
2-yl)quinazoline (26aq). Yield 68%. 1H NMR (400 MHz,
CDCl3) δ 8.02 (d, J = 4.0 Hz, 1H), 7.94-7.88 (m, 2H), 7.78
(d, J=8.0 Hz, 1H), 7.72 (t, J=8.0 Hz, 1H), 7.45 (d, J=4.0 Hz,
1H), 7.40 (t, J=8.0 Hz, 1H), 7.15 (t, J=4.0 Hz, 1H), 7.05-6.95
(m, 2H), 3.92 (t, J = 4.0 Hz, 4H), 3.45 (t, J = 4.0 Hz, 4H). MS
(ESI) m/z 473 [C22H18F2N4O2S2 þ H]þ.
4-(4-(3,5-Dimethylphenylsulfonyl)piperazin-1-yl)-2-(thiophen-
2-yl)quinazoline (26ae). Yield 64%. 1H NMR (400 MHz, CDCl3)
δ 8.00 (d, J=3.2 Hz, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.76-7.69 (m,
2H), 7.46 (d, J = 4.8 Hz, 1H), 7.40-7.36 (m, 3H), 7.22 (s, 1H),
7.15 (t, J=4.4 Hz, 1H), 3.92 (t, J=4.8 Hz, 4H), 3.26 (t, J=4.4 Hz,
4H), 2.39 (s, 6H). MS (ESI) m/z 465 [C24H24N4O2S2 þ H]þ.
4-(4-(2,4-Dimethylphenylsulfonyl)piperazin-1-yl)-2-(thiophen-
2-yl)quinazoline (26af). Yield 62%. 1H NMR (400 MHz, CDCl3)
δ 8.00 (d, J =3.2 Hz, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.76-7.69
(m, 2H), 7.46 (d, J = 4.8 Hz, 1H), 7.40-7.362 (m, 3H), 7.22
(s, 1H), 7.15 (t, J=4.4 Hz, 1H), 3.92 (t, J=4.8 Hz, 4H), 3.26 (t, J=
4.4 Hz, 4H), 2.39 (s, 6H). MS (ESI) m/z465 [C24H24N4O2S2 þ H]þ.
4-(4-(3-tert-Butylphenylsulfonyl)piperazin-1-yl)-2-(thiophen-
2-yl)quinazoline (26ag). Yield 66%. 1H NMR (400 MHz, CDCl3)
δ 7.99 (d, J= 4.0 Hz, 1H), 7.89 (d, J= 8.0 Hz, 1H), 7.79 (s, 1H),
7.75-7.68 (m, 2H), 7.62 (t, J = 8.0 Hz, 2H), 7.49-7.44 (m, 2H),
7.37 (t, J=8.0 Hz, 1H), 7.14 (d, J=4.0 Hz, 1H), 3.92 (t, J=4.0Hz,
4H), 3.26 (t, J = 4.0 Hz, 4H), 1.34 (s, 9H). MS (ESI) m/z 481
[C26H28N4O2S2 þ H]þ.
4-(4-(2-Chlorophenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-yl)-
quinazoline (26ar). Yield 67%. 1H NMR (400 MHz, CDCl3) δ
8.10 (d, J = 4.0 Hz, 1H), 8.01 (d, J = 2.8 Hz, 1H), 7.91 (d, J =
8.4 Hz), 7.80 (d, J=8.0 Hz, 1H), 7.72 (t, J=7.6 Hz, 1H), 7.56-
7.38 (m, 5H), 7.15 (t, J=4 Hz, 1H), 3.89 (t, J=4.4 Hz, 4H), 3.57
(t, J=4.8 Hz, 4H). MS (ESI) m/z 471 [C22H19ClN4O2S2]þ.
4-(4-(3-Chlorophenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-yl)-
quinazoline (26as). Yield 30%. 1H NMR (400 MHz, CDCl3) δ
8.01 (br s, 1H), 7.91 (d, J=8.0 Hz, 1H), 7.80 (s, 1H), 7.76-7.68
(m, 3H), 7.59 (d, J=8.0 Hz, 1H), 7.53-7.46 (m, 2H), 7.39 (t, J=
8.0 Hz, 1H), 7.15 (br s, 1H), 3.92 (br s, 4H), 3.30 (br s, 4H). MS
(ESI) m/z 471 [C22H19ClN4O2S2]þ.
4-(4-(3,5-Dichlorophenylsulfonyl)piperazin-1-yl)-2-(thiophen-
2-yl)quinazoline (26at). Yield 59%. 1H NMR (400 MHz, CDCl3)
δ 8.01 (d, J=3.6 Hz, 1H), 7.92 (d, J=8.4 Hz, 1H), 7.77-7.70 (m,
2H), 7.67 (s, 2H), 7.59 (s, 1H), 7.46 (d, J=5.2 Hz, 1H), 7.40 (t, J=
8.0 Hz, 1H), 7.15 (t, J=4.4 Hz, 1H), 3.92 (t, J=4.8 Hz, 4H), 3.32
(t, J=4.4 Hz, 4H). MS (ESI) m/z 506 [C22H18Cl2N4O2S2 þ H]þ.
1-(2-(4-(2-(Thiophen-2-yl)quinazolin-4-yl)piperazin-1-ylsulfo-
4-(4-(4-tert-Butylphenylsulfonyl)piperazin-1-yl)-2-(thiophen-
2-yl)quinazoline (26ah). Yield 63%. 1H NMR (400 MHz,
CDCl3) δ 8.00 (d, J = 4.0 Hz, 1H), 7.89 (d, J = 8.0 Hz, 1H),
7.75-7.68 (m, 4H), 7.55 (d, J=8.0 Hz, 2H), 7.46 (d, J=4.0 Hz,
1H), 7.37 (t, J = 8.0 Hz, 1H), 7.27 (s, 1H), 7.14 (t, J = 4.0 Hz,
1H), 3.91 (t, J = 4.0 Hz, 4H), 3.28 (t, J = 4.0 Hz, 4H), 1.33
(s, 9H). MS (ESI) m/z 481 [C26H28N4O2S2 þ H]þ.
1
nyl)phenyl)ethanone (26ba). Yield 60%. H NMR (400 MHz,
CDCl3) δ 8.01 (d, J = 3.2 Hz, 1H), 7.90 (d, J = 8.4 Hz, 2H),
7.73-7.69 (m, 2H), 7.62 (t, J=7.2 Hz, 1H), 7.54 (t, J=7.6 Hz,
1H), 7.45 (d, J=5.2 Hz, 1H), 7.40-7.32 (m, 2H), 7.14 (t, J=4.4
Hz, 1H), 3.87 (t, J=4.4 Hz, 4H), 3.40 (t, J=4.8 Hz, 4H), 2.47 (s,
3H). MS (ESI) m/z 479 [C24H22N4O3S2 þ H]þ.
4-(4-(2-Methoxyphenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-yl)-
1
1-(3-(4-(2-(Thiophen-2-yl)quinazolin-4-yl)piperazin-1-ylsulfo-
quinazoline (26ai). Yield 63%. H NMR (400 MHz, CDCl3) δ
1
nyl)phenyl)ethanone (26bb). Yield 65%. H NMR (400 MHz,
8.02 (d, J=4.0 Hz, 1H), 7.94-7.89 (m, 2H), 7.79 (d, J=4.0 Hz,
1H), 7.71 (t, J=8.0 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H), 7.45 (d, J=
4.0 Hz, 1H), 7.39 (t, J = 8.0 Hz, 1H), 7.14 (t, J = 4.0 Hz, 1H),
7.07-7.00 (m, 2H), 3.92 (s, 3H), 3.90 (t, J = 4.0 Hz, 4H), 3.49
(t, J=4.0 Hz, 4H). MS (ESI) m/z 467 [C23H22N4O3S2 þ H]þ.
4-(4-(3-Methoxyphenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-
yl)quinazoline (26aj). Yield 38%. 1H NMR (400 MHz, CDCl3) δ
8.02 (br s, 1H), 7.91(d, J=8.0 Hz, 1H), 7.75-7.69 (m, 2H), 7.48-
7.44 (m, 2H), 7.38 (t, J=6.0 Hz, 2H), 7.30 (s, 1H), 7.16-7.12 (m,
2H), 3.92 (s, 4H), 3.86 (s, 3H), 3.29 (t, J=4.0 Hz, 4H). MS (ESI)
m/z 467 [C23H22N4O3S2 þ H]þ.
CDCl3) δ 8.01 (d, J = 3.2 Hz, 1H), 7.90 (d, J = 8.4 Hz, 2H),
7.73-7.69 (m, 2H), 7.62 (t, J=7.2 Hz, 1H), 7.54 (t, J=7.6 Hz,
1H), 7.45 (d, J=5.2 Hz, 1H), 7.40-7.32 (m, 2H), 7.14 (t, J=4.4
Hz, 1H), 3.87 (t, J=4.4 Hz, 4H), 3.40 (t, J=4.8 Hz, 4H), 2.47 (s,
3H). MS (ESI) m/z 479 [C24H22N4O3S2 þ H]þ.
Ethyl 2-(4-(2-(Thiophen-2-yl)quinazolin-4-yl)piperazin-1-
ylsulfonyl)benzoate (26be). Yield 45%. 1H NMR (400 MHz,
CDCl3) δ 8.01 (d, J= 3.2 Hz, 1H), 7.89 (t, J = 8.8 Hz, 2H), 7.77
(d, J=8.4 Hz, 1H), 7.71 (t, J=7.2 Hz, 1H), 7.62 (t, J=6.8 Hz,
2H), 7.51 (d, J=8.4 Hz, 1H), 7.45 (d, J=4.8 Hz, 1H), 7.38 (t, J=
8.0 Hz, 1H), 7.15 (t, J=4.0 Hz, 1H), 4.44 (q, J=7.2 Hz, 2H), 3.90
(t, J=4.4 Hz, 4H), 3.48 (t, J=4.4 Hz, 4H), 1.42 (t, J=7.2 Hz,
3H). MS (ESI) m/z MS (ESI) m/z 509 [C25H24N4O4S2 þ H]þ.
2-(4-(2-(Thiophen-2-yl)quinazolin-4-yl)piperazin-1-ylsulfo-
nyl)benzonitrile (26bj). Yield 75%. 1H NMR (400 MHz, CDCl3)
δ 8.10 (d, J=8.0 Hz, 1H), 8.01 (d, J=3.6 Hz, 1H), 7.91 (d, J=
8.0 Hz, 2H), 7.81-7.71 (m, 4H), 7.46-7.27 (m, 2H), 7.15 (t, J=
4.0 Hz, 1H), 3.93 (t, J=4.8 Hz, 4H), 3.53 (t, J=4.8 Hz, 4H). MS
(ESI) m/z 462 [C23H19N5O2S2 þ H]þ.
4-(4-(4-Methoxyphenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-
yl)quinazoline (26ak). Yield 57%. 1H NMR (400 MHz, CDCl3)
δ 8.01 (br s, 1H), 7.90 (d, J = 4.0 Hz, 1H), 7.75-7.69 (m, 4H),
7.46 (d, J=4.0 Hz, 1H), 7.37 (t, J=6.0 Hz, 1H), 7.15 (t, J=4.0
Hz, 1H), 7.01 (d, J=4.0 Hz, 1H), 3.92 (s, 4H), 3.86 (s, 3H), 3.25
(t, J= 6.0 Hz, 4H). MS (ESI) m/z 467 [C23H22N4O3S2 þ H]þ.
4-(4-(2-Fluorophenylsulfonyl)piperazin-1-yl)-2-(thiophen-2-yl)-
quinazoline (26an). Yield 71%. 1H NMR (400 MHz, CDCl3) δ
8.01 (d, J=3.2 Hz, 1H), 7.91-7.88 (m, 2H), 7.77 (d, J=8.0 Hz,
1H), 7.72(t, J=7.6 Hz, 1H), 7.62-7.57 (m, 1H), 7.45 (d, J=4.8Hz,
1H), 7.39 (t, J=7.6 Hz, 1H), 7.33-7.24 (m, 2H), 7.15 (t, J=4.4 Hz,
3-(4-(2-(Thiophen-2-yl)quinazolin-4-yl)piperazin-1-ylsulfonyl)-
1
benzonitrile (26bk). Yield 70%. H NMR (400 MHz, CDCl3)