6270 Journal of Medicinal Chemistry, 2007, Vol. 50, No. 24
Perez-Medrano et al.
1
(ESI+) m/z 455 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-
cyanoguanidino]propyl}benzamide (26). mp 194-195 °C; MS
2.16 (s, 3H), 3.86 (s, 3 H), 6.50 (t, J ) 8 Hz, 1 H), 6.82 (d, J ) 9
Hz, 1 H), 7.07 (dd, J ) 7, 5 Hz, 1 H), 7.60-7.64 (m, 3 H), 7.84
(d, J ) 8 Hz, 2 H), 8.14 (dd, J ) 5, 2 Hz, 1 H), 8.77 (d, J ) 8 Hz,
1 H), 9.45 (s, 1 H). Anal. (C18H17Cl3N6O2) C, H, N.
4-Chloro-N-{2,2-dichloro-1-[N′-cyano-N′′-(2-methyl-6-(trif-
luoromethyl)-3-yl)guanidino]propyl}benzamide (17). mp 115-
116 °C; MS (ESI+) m/z 507 (M + H)+; 1H NMR (300 Mz, DMSO-
d6) δ 2.17 (s, 3 H), 3.31 (s, obscured, 3 H), 6.16 (t, J ) 8.0 Hz, 1
H), 7.13 (d, J ) 8.0 Hz, 1 H), 7.62 (d, J ) 8.0 Hz, 2 H), 7.86 (d,
J ) 9.0 Hz, 2 H), 7.81-7.90 (m, 2 H), 8.80 (d, J ) 8.0 Hz, 1 H),
9.79 (s, 1 H). Anal. (C19H16Cl3F3N6O) C, H, N.
1
(ESI+) m/z 426 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
ppm 2.18 (s, 3 H), 6.56 (t, J ) 8.65 Hz, 1 H), 7.32 (d, J ) 9.15
Hz, 1 H), 7.52 (m, 2 H), 7.60 (d, J ) 7.12 Hz, 2 H), 7.77 (dd, J )
8.48, 2.71 Hz, 1 H), 7.82 (m, 2 H), 8.35 (d, J ) 2.37 Hz, 1 H),
8.63 (d, J ) 9.49 Hz, 1 H), 9.99 (s, 1 H). Anal. (C17H15Cl3N6O) C,
H, N.
3-Chloro-N-{2,2-dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-
cyanoguanidine]propyl}benzamide (27). mp 138-140 °C; MS
1
(ESI+) m/z 460 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
2.19 (s, 3H), 6.54 (dd, J ) 8.8, 8.8 Hz, 1H), 7.32 (d, J ) 9.2 Hz,
1H), 7.54 (d, J ) 5.8 Hz, 1H), 7.61 (d, J ) 5.8 Hz, 1H), 7.68 (m,
1H); 7.78 (m, 2H), 7.85 (m, 1H), 8.35 (d, J ) 2.4 Hz, 1H), 8.80
(d, J ) 8.1 Hz, 1H), 9.98 (s, 1H). Anal. (C17H14Cl4N6O) C, H, N.
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-cyanoguani-
dino]propyl}-3-methylbenzamide (28). mp 145-146 °C; MS
4-Chloro-N-{2,2-dichloro-1-[N′-cyano-N′′-(6-methoxypyridin-
3-yl)guanidino]propyl}benzamide (18). mp 209-210 °C; MS
1
(ESI+) m/z 456 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
ppm 2.14 (s, 3 H), 3.87 (s, 3 H), 6.51 (t, J ) 8.65 Hz, 1 H), 6.81
(d, J ) 8.81 Hz, 1 H), 6.92 (d, J ) 8.81 Hz, 1 H), 7.63 (m, 3 H),
7.83 (d, J ) 8.81 Hz, 2 H), 8.10 (d, J ) 2.37 Hz, 1 H), 8.72 (d, J
) 8.48 Hz, 1 H), 9.67 (s, 1 H). Anal. (C18H17Cl3N6O2) C, H, N.
4-Chloro-N-{2,2-dichloro-1-[N′-cyano-N′′-(2-fluorophenyl)-
guanidino]propyl}benzamide (19). mp 216-217 °C; MS (ESI+)
1
(ESI+) m/z 439 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
2.17 (s, 3 H), 2.38 (s, 3H), 6.56 (dd, J ) 8.5, 8.8 Hz, 1 H), 7.35 (d,
J ) 9.2 Hz, 1 H), 7.42 (m, 2 H), 7.50-7.64 (m, 3 H), 7.78 (dd, J
) 2.7, 8.5 Hz, 1 H), 8.36 (d, J ) 2.7 Hz, 1 H), 8.59 (d, J ) 8.5
Hz, 1 H), 10.0 (s, 1 H). Anal. (C18H17Cl3N6O) C, H, N.
m/z 442 (M + H)+; H NMR (300 MHz, DMSO-d6) δ ppm 2.14
1
(s, 3 H), 6.52 (t, J ) 8.65 Hz, 1 H), 6.88 (d, J ) 8.82 Hz, 1 H),
7.28 (m, 1 H), 7.38 (m, 3 H), 7.61 (d, J ) 8.48 Hz, 2 H), 7.85 (d,
J ) 8.48 Hz, 2 H), 8.84 (d, J ) 8.48 Hz, 1 H), 9.68 (s, 1 H). Anal.
(C18H15Cl3FN5O) C, H, N.
Thiophene-2-carboxylic Acid {2,2-Dichloro-1-[N′-(6-chloro-
pyridin-3-yl)-N′′-cyanoguanidino]propyl}amide (29). mp 201-
1
203 °C; MS (ESI+) m/z 431 (M + H)+; H NMR (300 MHz,
DMSO-d6) δ 2.17 (s, 3H); 6.49 (t, J ) 8.5 Hz, 1H); 7.22 (dd, J )
5.1, 3.9 Hz, 1H), 7.30 (br d, J ) 8.5 Hz, 1H); 7.60 (d, J ) 8.5 Hz,
1H), 7.60 (d, J ) 8.7 Hz, 2H), 7.74-7.80 (m, 2H), 7.89 (dd, J )
4.8, 1.0 Hz, 1H), 8.35 (d, J ) 2.7 Hz, 1H), 8.62 (br d, J ) 8.5 Hz,
1H), 9.88 (s, 1H). Anal. (C15H13Cl3N6OS) C, H, N.
4-Bromo-N-{2,2-dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-
cyanoguanidino]propyl}benzamide (20). mp 215-216 °C; MS
1
(ESI+) m/z 503 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
ppm 2.18 (s, 3 H), 6.54 (t, J ) 8.65 Hz, 1 H), 7.31 (d, J ) 8.82
Hz, 1 H), 7.60 (d, J ) 8.48 Hz, 1 H), 7.76 (m, 4 H), 7.79 (d, J )
2.71 Hz, 1 H), 8.35 (d, J ) 2.71 Hz, 1 H), 8.72 (d, J ) 8.48 Hz,
1 H), 9.98 (s, 1 H). Anal. (C17H14BrCl3N6O) C, H, N.
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-cyanoguani-
dino]propyl}-4 -trifluoromethylbenzamide (30). mp 210-211 °C;
MS (ESI+) m/z 493 (M + H)+; 1H NMR (300 MHz, DMSO-d6) δ
2.10 (s, 3H), 6.56 (t, J ) 8.6 Hz, 1H), 7.32 (d, J ) 8.1 Hz, 1H),
7.59 (d, J ) 8.7 Hz, 1H), 7.78 (dd, J ) 8.5, 2.7 Hz, 1H), 7.92 (d,
J ) 8.9 Hz, 2H), 8.03 (d, J ) 8.9 Hz, 2H), 8.35 (d, J ) 2.5 Hz,
1H), 8.88 (d, 1H, J ) 7.8 Hz, 1H), 9.97 (br s, 1H). Anal. (C18H14-
Cl3F3N6O) C, H, N.
3,5-Dichloro-N-{2,2-dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-
cyanoguanidine]propyl}benzamide (21). mp 138-140 °C; MS
1
(ESI+) m/z 492 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
2.20 (s, 3H), 6.52 (t, J ) 8.6 Hz, 1H), 7.31 (d, J ) 8.7 Hz, 1H),
7.60 (d, J ) 8.5 Hz, 1H), 7.77 (dd, J ) 8.5, 2.9 Hz, 1H), 7.83 (app
d, J ) 1.7 Hz, 2H), 7.87-7.92 (m, 1H), 8.35 (d, J ) 3.1 Hz, 1H),
8.90 (d, J ) 8.6 Hz, 1H), 9.97 (br s, 1 H). Anal. (C17H13Cl5N6O)
C, H, N.
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-cyanoguani-
dino]propyl}-3-fluorobenzamide (31). mp 191-192 °C; MS
1
(ESI+) m/z 443 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
2.19 (s, 3H), 6.54 (dd, J ) 8.5, 8.8 Hz, 1H), 7.30 (d, J ) 8.8 Hz,
3H), 7.69-7.44 (m, 5H), 7.77 (dd, J ) 2.7, 8.5 Hz, 1H), 8.35 (d,
J ) 2.7 Hz, 1H), 8.76 (d, J ) 8.1 Hz, 1H), 9.98 (s, 1H). Anal.
(C17H14Cl3FN6O) C, H, N.
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-cyanoguani-
dino]propyl}-4-iodobenzamide (22). mp 222-224 °C; MS (ESI+)
1
m/z 552 (M + H)+; H NMR (300 MHz, DMSO-d6) δ ppm 2.17
(s, 3 H), 6.53 (t, J ) 8.65 Hz, 1 H), 7.31 (d, J ) 8.82 Hz, 1 H),
7.60 (d, J ) 8.14 Hz, 3 H), 7.77 (dd, J ) 8.48, 2.71 Hz, 1 H), 7.93
(d, J ) 8.14 Hz, 2 H), 8.35 (d, J ) 2.71 Hz, 1 H), 8.69 (d, J )
8.48 Hz, 1 H), 9.98 (s, 1 H). Anal. (C17H14Cl3IN6O) C, H, N.
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-cyanoguani-
dino]propyl}-4-methylbenzamide (23). mp 198-200 °C; MS
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-cyanoguani-
dino]propyl}-4-trifluoromethoxybenzamide (32). mp 198-
1
199 °C; MS (ESI+) m/z 510 (M + H)+; H NMR (300 MHz,
DMSO-d6) δ ppm 9.98 (s, 1 H), 8.76 (d, J ) 8.14 Hz, 1 H), 8.35
(d, J ) 2.37 Hz, 1 H), 7.96 (dd, J ) 8.81, 2.71 Hz, 1 H), 7.60 (d,
J ) 8.48 Hz, 1 H), 7.53 (d, J ) 7.80 Hz, 2 H), 7.31 (d, J ) 8.81
Hz, 1 H), 6.54 (t, J ) 8.65 Hz, 1 H), 2.19 (s, 3 H). Anal. (C18H14-
Cl3F3N6O2) C, H, N.
1
(ESI+) m/z 439 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
2.17 (s, 3 H), 2.37 (s, 3 H), 6.55 (dd, J ) 8.8, 8.8 Hz, 1 H), 7.35
(d, J ) 7.8 Hz, 3 H), 7.60 (d, J ) 8.5 Hz, 1 H), 7.74 (d, J ) 8.5
Hz, 2 H), 7.77 (dd, J ) 2.7, 8.5 Hz, 1 H), 8.35 (d, J ) 2.4 Hz, 1
H), 8.52 (d, J ) 8.47 Hz, 1 H), 9.99 (s, 1 H). Anal. (C18H17Cl3N6O)
C, H, N.
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-cyanoguani-
dino]propyl}-2-methoxyisonicotinamide (33). mp 172-173 °C;
MS (ESI+) m/z 457 (M + H)+; 1H NMR (300 MHz, DMSO-d6) δ
ppm 2.18 (s, 3 H), 3.90 (s, 3 H), 6.51 (t, J ) 8.65 Hz, 1 H), 7.16
(s, 1 H), 7.27 (s, 1 H), 7.31 (dd, J ) 5.43, 1.36 Hz, 1 H), 7.60 (d,
J ) 8.48 Hz, 1 H), 7.77 (dd, J ) 8.82, 2.71 Hz, 1 H), 8.35 (d, J )
4.75 Hz, 2 H), 8.88 (d, J ) 8.14 Hz, 1 H), 9.98 (s, 1 H). Anal.
(C17H16Cl3N7O2) C, H, N.
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-cyanoguani-
dino]propyl}-3, 5-dimethoxybenzamide (34). mp 193-195 °C;
MS (ESI+) m/z 485 (M + H)+; 1H NMR (300 MHz, DMSO-d6) δ
2.17 (s, 3H), 3.80 (s, 6H), 6.52 (t, J ) 8.7 Hz1H), 6.75 (d, J ) 1.3
Hz, 1H), 6.95 (d, J ) 2.1 Hz, 2H), 7.27 (d, J ) 8.8 Hz, 1H), 7.60
(d, J ) 8.5 Hz, 1H), 7.78 (dd, J ) 8.5, 2.7 Hz, 1H), 8.36 (d, J )
5.5 Hz, 1H), 8.59 (d, J ) 8.6 Hz, 1H), 9.96 (br s, 1H). Anal.
(C19H19Cl3N6O3) C, H, N.
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-cyanoguani-
dino]propyl}-3,5-difluorobenzamide (24). mp 195-196 °C; MS
1
(ESI+) m/z 461 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
2.19 (s, 3 H), 6.52 (t, J ) 8.6 Hz, 1 H), 7.30 (d, J ) 8.5 Hz, 1 H),
7.77 (dd, J ) 8.5, 2.7 Hz, 1 H), 7.52-7.63 (m, 4 H), 8.35 (d, J )
2.5 Hz, 1 H), 8.88 (d, J ) 7.8 Hz, 1 H), 10.00 (br s, 1 H). Anal.
(C17H13Cl3F2N6O) C, H, N.
N-{2,2-Dichloro-1-[N′-(6-chloropyridin-3-yl)-N′′-cyanoguani-
dino]propyl}-4-fluorobenzamide (25). mp 197-198 °C; MS
1
(ESI+) m/z 443 (M + H)+; H NMR (300 MHz, DMSO-d6) δ
2.18 (s, 3 H), 6.54 (t, J ) 8.6 Hz, 1 H), 7.27 (br d, J ) 8.0 Hz, 1
H), 7.37 (d, J ) 8.8 Hz, 2 H), 7.59 (d, 8.8 Hz, 1 H), 7.77 (dd, J )
8.5, 2.7 Hz, 1 H), 7.91 (dd, J ) 8.7, 5.3 Hz, 2 H), 8.34 (d, J ) 2.5
Hz, 1 H), 8.66 (d, J ) 7.8 Hz, 1 H), 9.96 (s, 1 H). Anal. (C17H14-
Cl3FN6O) C, H, N.
N-{2,2-Dichloro-1-[N′-cyano-N′′-(6-trifluoromethylpyridin-3-
yl)-guanidino]propyl}-3,5-difluorobenzamide (35). mp 202-