Inhibition of CAMs in Human Endothelial Cells
J ournal of Medicinal Chemistry, 2001, Vol. 44, No. 21 3481
2H), 7.47 (d, J ) 9 Hz, 2H, 8.13 (s, 1H), 8.17 (s, 1H), 8.91 (t,
J ) 6 Hz, 1H), 9.15 (s, 1H); MS (DCI/NH3) m/e 333 (M + H)+,
303.
2.4 Hz, 1H), 7.50 (d, J ) 2.6 Hz, 1H), 7.88 (br s, 1H), 7.93 (s,
1H), 8.22 (s, 1H), 8.46 (br s, 1H), 9.09 (s, 1H); MS (DCI/NH3)
m/z 319 (M + H)+.
Da ta for 4-(4-Ch lor op h en oxy)-N,N-d im eth ylth ien o[2,3-
c]p yr id in e-2-ca r boxa m id e (18): 1H NMR (300 MHz, DMSO-
d6) δ 3.03 (br s, 3H), 3.12 (br s, 3H), 7.17 (d, J ) 7.5 Hz, 2H),
7.46 (d, J ) 7.5 Hz, 2H), 7.62 (s, 1H), 8.18 (s, 1H), 9.15 (s,
1H); 13C NMR (400 Hz, DMSO-d6) δ 29.5, 119.8, 119.9, 127.8,
Da t a for 4-(2-Br om o-4-ch lor op h en oxy)t h ien o[2,3-c]-
p yr id in e-2-ca r boxa m id e (30): 1H NMR (300 MHz, DMSO-
d6) δ 7.18 (d, J ) 8.8 Hz, 1H), 7.49 (dd, J ) 8.8, 2.6 Hz, 1H),
7.90 (br s, 1H), 7.98 (s, 2H), 8.23 (s, 1H), 8.49 (br s, 1H), 9.14
(s, 1H); MS (DCI/NH3) m/z 383 (M + H)+. Anal. (C14H8-
BrClN2O2S) C, H, N.
129.9, 133.0, 136.3, 136.3, 140.8,143.6,147.3,155.4, 162.3; MS
+
(APCI) m/e 333 (M + H)
.
Da ta for 4-[2-(2-P r op en yl)p h en oxy]th ien o[2,3-c]p yr i-
d in e-2-ca r boxa m id e (31): 1H NMR (300 MHz, DMSO-d6) δ
3.43 (d, J ) 6.6 Hz, 2H), 5.01 (m, 1H), 5.05 (m, 1H), 5.98 (ddt,
J ) 17.6, 10.0, 6.6 Hz, 1H), 7.00 (dd, J ) 8.0, 1.4 Hz, 1H),
7.27 (m, 2H), 7.39 (dd, J ) 7.4, 1.9 Hz, 1H), 7.82 (s, 1H), 7.88
(br s, 1H), 8.27 (s, 1H), 8.49 (br s, 1H), 9.05 (s, 1H); MS (DCI/
NH3) m/z 311 (M + H)+. Anal. (C17H14N2O2S) C, H, N.
Da t a for 4-[2-(2,3-Dih yd r oxyp r op yl)p h en oxy]t h ien o-
[2,3-c]p yr id in e-2-ca r boxa m id e (32): 1H NMR (300 MHz,
DMSO-d6) δ 2.60 (dd, J ) 13.4, 8.4 Hz, 1H), 2.88 (dd, J ) 13.4,
4.6 Hz, 1H), 3.29 (t, J ) 5.6 Hz, 2H), 3.76 (m, 1H), 4.55 (t, J
) 5.1 Hz, 1H), 4.63 (d, J ) 5.1 Hz, 1H), 6.94 (dd, J ) 7.7, 1.3
Hz, 1H), 7.22 (m, 2H), 7.45 (dd, 1H), 7.84 (s, 1H), 7.88 (br s,
1H), 8.26 (s, 1H), 8.46 (br s, 1H), 9.04 (s, 1H); MS (DCI/NH3)
m/z 345 (M + H)+. Anal. (C17H16N2O4S) C, H, N.
Da t a for 4-(4-Ch lor op h en oxy)-N-(2-h yd r oxyet h yl)-
th ien o[2,3-c]p yr id in e-2-ca r boxa m id e (19): 1H NMR (400
MHz, DMSO-d6) δ 3.33 (m, 2H), 3.51 (m, 2H), 5.76 (t, J ) 6.0
Hz, 1H), 7.12 (d, J ) 8.0 Hz, 2H), 7.26 (d, J ) 8.0 Hz, 2H),
8.17 (s, 2H), 8.98 (br.t, J ) 6.0 Hz, 1H), 9.14 (s, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 42.3, 59.4, 119.2, 119.3, 127.6, 130.0,
133.2, 137.5, 137.9, 141.4, 146.4, 147.1, 155.6, 160.6; MS (DCI/
+
NH3) m/z 349 (M + H)
.
Da t a for 4-(4-Br om op h en oxy)-N-(2-h yd r oxyet h yl)-
th ien o[2,3-c]p yr id in e-2-ca r boxa m id e (20): mp 158-159
°C; 1H NMR (300 MHz, DMSO-d6) δ 3.32 (m, 2H), 3.51 (m,
3H), 4.79 (t, J ) 5.9 Hz, 1H), 7.06 (d, J ) 8.8 Hz, 2H), 7.59 (d,
J ) 8.8 Hz, 2H), 8.17 (s, 1H), 8.20 (s, 1H), 9.02 (t, J ) 5.5 Hz,
1H), 9.17 (s, 1H). MS (DCI/NH3) m/e 393, 395 (M + H)+. Anal.
(C16H13BrN2O3S) C, H, N.
Da ta for 4-(3-Ch lor op h en oxy)th ien o[2,3-c]p yr id in e-2-
ca r boxa m id e (21): 1H NMR (300 MHz, DMSO-d6) δ 7.04 (m,
1H), 7.27 (m, 2H), 7.45 (br s, 1H), 7.87 (br s, 1H), 8.15 (d, 1H),
8.21 (s, 1H), 8.45 (br s, 1H), 9.18 (s, 1H); MS (DCI/NH3) m/z
305 (M + H)+.
Da ta for 4-(3-Br om op h en oxy)th ien o[2,3-c]p yr id in e-2-
ca r boxa m id e (22): 1H NMR (300 MHz, DMSO-d6) δ 7.07 (dt,
J ) 7.1, 2.0 Hz, 1H), 7.36-7.39 (m, 3H), 7.87 (br s, 1H), 8.15
(s, 1H), 8.20 (s, 1H), 8.45 (br s, 1H), 9.17 (s, 1H); MS (DCI/
NH3) m/z 349, 351 (M + H)+. Anal. (C14H9N2O2S‚CH3OH) C,
H, N.
Da ta for 4-P h en oxyth ien o[2,3-c]p yr id in e-2-ca r boxa -
m id e (33): 1H NMR (300 MHz, DMSO-d6) δ 7.15 (dd, 2H),
7.20 (t, 1H), 7.45 (t, 2H), 7.85 (br s, 1H), 8.10 (s, 1H), 8.20 (s,
1H), 8.45 (br s, 1H), 9.15 (s, 1H); MS (DCI/NH3) m/z 271 (M +
H)+. Anal. (C14H10N2O2S) C, H, N.
Da ta for 4-(4-Eth en ylp h en oxy)th ien o[2,3-c]p yr id in e-
1
2-ca r boxa m id e (34): H NMR (300 MHz, DMSO-d6) δ 5.24
(d, J ) 10.1 Hz, 1H), 5.79 (d, J ) 17.6 Hz, 1H), 6.75 (dd, J )
17.6, 10.1 Hz, 1H), 7.10 (d, J ) 8.8 Hz, 2H), 7.54 (d, J ) 8.8
Hz, 2H), 7.87 (br s, 1H), 8.12 (s, 1H), 8.18 (s, 1H), 8.45 (br s,
1H), 9.13 (s, 1H); MS (DCI/NH3) m/z 297 (M + H)+. Anal.
(C16H12N2O2S‚0.25CH3OH) C, H, N.
Da ta for 4-[3-(Tr iflu or om eth yl)p h en oxy]th ien o[2,3-c]-
p yr id in e-2-ca r boxa m id e (23): mp 175-176 °C; 1H NMR
(300 MHz, DMSO-d6) δ 2.80 (d, J ) 3.7 Hz, 3H), 7.35 (d, J )
8.0 Hz, 1H), 7.55 (m, 2H), 7.65 (t, J ) 8.0 Hz, 1H), 8.10 (s,
1H), 8.30 (s, 1H), 9.00 (br s, 2H), 9.25 (s, 1H); MS (DCI/NH3)
m/e 353 (M + H)+. Anal. (C16H11F3N2O2S‚0.25 H2O) C, H, N.
Da t a for E t h yl 3-{[2-(Am in oca r b on yl)t h ien o[2,3-c]-
pyr idin -4-yl]oxy}ben zoate (24): 1H NMR (300 MHz, DMSO-
d6) δ 1.30 (t, J ) 7.1 Hz, 3 H), 4.31 (q, J ) 7.1 Hz, 2 H), 7.39
(ddd, J ) 8.3, 2.5, 1.0 Hz, 1 H), 7.58 (m, 2 H), 7.79 (dt, J )
7.8, 1.2 Hz, 1H), 7.83 (br s, 1H), 8.15 (s, 1 H), 8.19 (s, 1 H),
8.42 (br s, 1H), 9.17 (s, 1H); MS (DCI/NH3) m/z 343 (M + H)+.
Da ta for 4-(4-Ch lor o-3-m eth ylp h en oxy)th ien o[2,3-c]-
p yr id in e-2-ca r boxa m id e (25): 1H NMR (300 MHz, DMSO-
d6) δ 2.32 (s, 3H), 6.95 (dd, J ) 8.7, 3.0 Hz, 1H), 6.97 (d, J )
3.0 Hz, 1H), 7.44 (d, J ) 8.7 Hz, 1H), 7.85 (br s, 1H), 8.13 (s,
1H), 8.16 (s, 1H), 8.45 (s, 1H), 9.14 (s, 1H); MS (DCI/NH3) m/z
319 (M + H)+.
Da ta for 4-(3-Ch lor o-4-m eth ylp h en oxy)th ien o[2,3-c]-
p yr id in e-2-ca r boxa m id e (26): 1H NMR (300 MHz, DMSO-
d6) δ 2.32 (s, 3H), 7.00 (dd, J ) 8.4, 2.6 Hz, 1H), 7.26 (d, J )
2.6 Hz, 1H), 7.39 (d, J ) 8.5 Hz, 1H), 7.86 (br s, 1H), 8.13 (s,
1H), 8.17 (s, 1H), 8.45 (br s, 1H), 9.14 (s, 1H); MS (DCI/NH3)
m/z 319 (M + H)+.
Da t a for 4-(4-Ch lor o-3-flu or op h en oxy)t h ien o[2,3-c]-
p yr id in e-2-ca r boxa m id e (27): mp 227-228 °C; 1H NMR
(300 MHz, DMSO-d6) δ 6.94 (m,1H), 7.34 (dd, J ) 3.0, 10.5
Hz, 1H), 7.60 (t, J ) 8.7 Hz, 1H), 7.87 (s, 1H), 8.11 (s, 1H),
8.26 (s, 1H), 8.44 (s, 1H), 9.19 (s, 1H); MS (DCI/NH3) m/e 323
(M + H)+. Anal. (C14H8N2ClFO2S) C, H, N.
Da ta for 4-(4-Eth ylp h en oxy)th ien o[2,3-c]p yr id in e-2-
ca r boxa m id e (35): 1H NMR (300 MHz, DMSO-d6) δ 1.19 (t,
J ) 7.5 Hz, 3H), 2.62 (q, J ) 7.5 Hz, 2H), 7.05 (dt, J ) 8.5, 2.0
Hz, 2H), 7.26 (dt, J ) 8.5, 2.0 Hz, 2H), 7.81 (br s, 1H), 8.07 (s,
1H), 8.21 (s, 1H), 8.43 (br s, 1H), 9.08 (s, 1H); MS (DCI/NH3)
m/z 299 (M + H)+. Anal. (C16H14N2O2S‚CH3OH) C, H, N.
Da t a for 4-[4-(1-Met h ylet h yl)p h en oxy]t h ien o[2,3-c]-
1
p yr id in e-2-ca r boxa m id e (36): H NMR (300 MHz, DMSO-
d6) δ 1.21 (d, J ) 6.8 Hz, 6H), 2.92 (septet, J ) 6.8 Hz, 1H),
7.05 (d, J ) 8.4 Hz, 2H), 7.30 (d, J ) 8.5 Hz, 2H), 7.82 (br s,
1H), 8.03 (s, 1H), 8.21 (s, 1H), 8.44 (br s, 1H), 9.09 (s, 1H); MS
(DCI/NH3) m/z 313 (M + H)+. Anal. (C17H16N2O2S) C, H, N.
Da ta for 4-(4-ter t-Bu tylp h en oxy)th ien o[2,3-c]p yr id in e-
2-ca r boxa m id e (37): 1H NMR (300 MHz, DMSO-d6) δ 1.29
(s, 9H), 7.04 (d, J ) 8.8 Hz, 2H), 7.44 (d, J ) 8.8 Hz, 2H), 7.82
(br s, 1H), 8.05 (s, 1H), 8.20 (s, 1H), 8.45 (br s, 1H), 9.09 (s,
1H); MS (DCI/NH3) m/z 327 (M + H)+.
Da ta for 4-(4-Octylp h en oxy)th ien o[2,3-c]p yr id in e-2-
ca r boxa m id e (38): 1H NMR (300 MHz, CDCl3) δ 0.88 (t, J )
6.6 Hz, 3H), 1.22-1.38 (m, 10H), 1.62 (m, 2H), 2.61 (t, J ) 7.6
Hz, 2H), 6.05 (br s, 2H), 6.99 (d, J ) 8.5 Hz, 2H), 7.20 (d, J )
8.5 Hz, 2H), 7.87 (s, 1H), 8.07 (br s, 1H), 8.92 (br s, 1H); MS
(DCI/NH3) m/z 383 (M + H)+. Anal. (C22H26N2O2S) C, H, N.
Da ta for 4-(4-F lu or op h en oxy)th ien o[2,3-c]p yr id in e-2-
ca r boxa m id e (39): 1H NMR (300 MHz, DMSO-d6) δ 7.26 (m,
4 H), 7.87 (br s, 1H), 8.04 (s, 1H), 8.21 (s, 1 H), 8.45 (br s, 1H),
9.10 (s, 1H); MS (DCI/NH3) m/z 289 (M + H)+.
Da ta for 4-(4-Br om op h en oxy)th ien o[2,3-c]p yr id in e-2-
ca r boxa m id e (40): 1H NMR (300 MHz, DMSO-d6) δ 7.08 (d,
J ) 8.8 Hz, 2H), 7.60 (d, J ) 8.8 Hz, 2H), 7.87 (br s, 1H), 8.14
(s, 1H), 8.17 (s, 1H), 8.45 (br s, 1H), 9.16 (s, 1H); MS (DCI/
NH3) m/z 349, 351 (M + H)+. Anal. (C14H9BrN2O2S‚0.75 CH3-
OH) C, H, N.
Da t a for 4-(4-Iod op h en oxy)t h ien o[2,3-c]p yr id in e-2-
ca r boxa m id e (41): 1H NMR (300 MHz, DMSO-d6) δ 6.94 (d,
J ) 8.8 Hz, 2H), 7.74 (d, J ) 8.8 Hz, 2H), 7.86 (br s, 1H), 8.13
(s, 1H), 8.17 (s, 1H), 8.44 (br s, 1H), 9.16 (s, 1H); MS (DCI/
NH3) m/z 397 (M + H)+. Anal. (C14H9IN2O2S) C, H, N.
Data for 4-(3,5-Dim eth ylph en oxy)th ien o[2,3-c]pyr idin e-
1
2-ca r boxa m id e (28): H NMR (300 MHz, DMSO-d6) δ 3.31
(s, 6H), 6.73 (s, 2H), 6.85 (s, 1H), 7.82 (br s, 1H), 8.05 (s, 1H),
8.18 (s, 1H), 8.43 (br s, 1H), 9.10 (s,1H); MS (DCI/NH3) m/z
299 (M + H)+.
Da ta for 4-(4-Ch lor o-2-m eth ylp h en oxy)th ien o[2,3-c]-
p yr id in e-2-ca r boxa m id e (29): 1H NMR (300 MHz, DMSO-
d6) δ 2.30 (s, 3H), 6.95 (d, J ) 8.6 Hz, 1H), 7.27 (dd, J ) 8.8,