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A. Varnavas et al. / European Journal of Medicinal Chemistry 40 (2005) 563–581
103.29, 113.22, 120.08, 120.65, 120.95, 122.49, 123.34,
124.82, 127.13, 127.20, 127.63, 127.92, 129.19, 129.51,
130.39, 132.16, 133.39, 137.44, 137.82, 139.07, 139.80,
140.45, 159.76, 169.65, 171.90.
yield. TLC (AcOEt/n-hexane 1:1) - Rf: 0.63; m.p. 185 °C;
1H-NMR (DMSO-d6) d 1.15 (t, 3H, –CH3); 3.19 (m, 2H,
–CH2–CH<); 4.14 (q, 2H, –CH2–O–); 4.78 (m, 1H, –CH<);
6.98 (s, 1H,Ar); 7.06–7.52 (m, 8H,Ar); 7.61 (t, 1H,Ar); 7.71
(d, 1H, Ar); 7.81 (d, 1H, Ar); 8.66 (d, 1H, Ar); 9.31 (d, 1H,
–NH–CH<); 11.96 (s, 1H, –NH–); 12.17 (s, 1H, –NH–); 13C-
NMR (DMSO-d6) d 13.97, 35.24, 54.34, 60.78, 102.57,
112.50, 114.80, 115.01, 119.30, 119.93, 120.20, 121.73,
122.56, 124.07, 126.95, 128.43, 130.92, 131.00, 131.52,
132.64, 133.58, 137.15, 139.17, 159.12, 159.85, 162.26,
168.93, 171.09.
4.1.6.6. 2-{2-[(1H-Indole-2-carbonyl)-amino]-benzoy-
lamino}-3-(2-methoxy-phenyl)-propionic acid ethyl ester
(6f). Trituration with hot MeOH afforded the titled com-
pound in 65% yield. TLC (AcOEt/n-hexane 1:1) - Rf: 0.68;
1
m.p. 197 °C; H-NMR (DMSO-d6) d 1.28 (t, 3H, –CH2–
CH3); 3.33 (m, 2H, –CH2–CH<); 3.98 (s, 3H, –O–CH3); 4.26
(q, 2H, –CH2–O–); 4.96 (m, 1H, –CH<); 6.98 (t, 1H, Ar);
7.14 (m, 2H, Ar); 7.21–7.37 (m, 5H, Ar); 7.65 (d, 1H, Ar);
7.75 (t, 1H, Ar); 7.87 (d, 1H, Ar); 7.94 (d, 1H, Ar); 8.80 (d,
1H,Ar); 9.38 (d, 1H, –NH–CH<); 11.95 (s, 1H, –NH–); 12.10
(s, 1H, –NH–); 13C-NMR (DMSO-d6) d 13.97, 31.40, 52.60,
55.33, 60.64, 102.59, 110.54, 112.50, 119.30, 119.87, 120.02,
120.21, 121.74, 122.52, 124.07, 125.02, 126.94, 128.16,
128.43, 130.76, 131.53, 132.60, 137.12, 139.15, 157.29,
159.09, 168.88, 171.38.
4.1.6.10. 3-(2-Chloro-phenyl)-2-{2-[(1H-indole-2-carbonyl)-
amino]-benzoylamino}-propionic acid ethyl ester (10f). Tritu-
ration with hot MeOH afforded the titled compound in 71%
yield. TLC (AcOEt/n-hexane 1:1) - Rf: 0.69; m.p. 207–
208 °C; 1H-NMR (DMSO-d6) d 1.16 (t, 3H, –CH3); 3.35 (m,
2H, –CH2–CH<); 4.15 (q, 2H, –CH2–O–); 4.87 (m, 1H,
–CH<); 6.98 (s, 1H, Ar); 7.07–7.53 (m, 8H, Ar); 7.62 (t, 1H,
Ar); 7.73 (d, 1H, Ar); 7.82 (d, 1H, Ar); 8.65 (d, 1H, Ar); 9.38
(d, 1H, –NH–CH<); 11.95 (s, 1H, –NH–); 12.10 (s, 1H,
–NH–); 13C-NMR (DMSO-d6) d 13.95, 34.01, 52.32, 60.94,
102.64, 112.50, 119.29, 119.97, 120.21, 121.76, 122.58,
124.08, 126.94, 126.99, 128.41, 128.64, 129.22, 131.48,
131.76, 132.67, 133.33, 134.90, 137.13, 139.12, 159.10,
168.94, 170.87.
4.1.6.7. 2-{2-[(1H-Indole-2-carbonyl)-amino]-benzoy-
lamino}-3-(3-methoxy-phenyl)-propionic acid ethyl ester
(7f). Trituration with hot MeOH afforded the titled com-
pound in 74% yield. TLC (AcOEt/n-hexane 1:1) - Rf: 0.64;
m.p. 178–179 °C; 1H-NMR (DMSO-d6) d 1.17 (t, 3H, –CH2–
CH3); 3.19 (m, 2H, –CH2–CH<); 3.67 (s, 3H, –O–CH3); 4.15
(q, 2H, –CH2–O–); 4.79 (m, 1H, –CH<); 6.70 (d, 1H, Ar);
6.94 (m, 3H, Ar); 7.22 (m, 4H, Ar); 7.50 (d, 1H, Ar); 7.61 (t,
1H, Ar); 7.71 (d, 1H, Ar); 7.82 (d, 1H, Ar); 8.66 (d, 1H, Ar);
9.30 (d, 1H, –NH–CH<); 11.96 (s, 1H, –NH–); 12.19 (s, 1H,
–NH–); 13C-NMR (DMSO-d6) d 14.01, 36.09, 54.30, 54.80,
60.80, 102.61, 112.04, 112.52, 114.70, 119.29, 119.91,
120.22, 121.32, 121.76, 122.53, 124.08, 126.95, 128.45,
129.20, 131.53, 132.66, 137.15, 139.00, 139.21, 159.14,
168.90, 171.19.
4.1.6.11. 3-(3-Chloro-phenyl)-2-{2-[(1H-indole-2-carbonyl)-
amino]-benzoylamino}-propionic acid ethyl ester (11f). Tritu-
ration with hot MeOH afforded the titled compound in 64%
yield. TLC (AcOEt/n-hexane 1:1) - Rf: 0.68; m.p. 207–
208 °C; 1H-NMR (DMSO-d6) d 1.15 (t, 3H, –CH3); 3.23 (m,
2H, –CH2–CH<); 4.14 (q, 2H, –CH2–O–); 4.80 (m, 1H,
–CH<); 6.97 (s, 1H, Ar); 7.06–7.52 (m, 8H, Ar); 7.61 (t, 1H,
Ar); 7.71 (d, 1H, Ar); 7.79 (d, 1H, Ar); 8.66 (d, 1H, Ar); 9.32
(d, 1H, –NH–CH<); 11.95 (s, 1H, –NH–); 12.12 (s, 1H,
–NH–); 13C-NMR (DMSO-d6) d 13.97, 35.62, 53.94, 60.83,
102.58, 112.49, 119.30, 119.94, 120.18, 121.73, 122.54,
124.05, 126.50, 126.94, 127.83, 128.36, 129.06, 129.93,
131.50, 132.65, 132.80, 137.13, 139.15, 140.00, 159.10,
168.87, 170.91.
4.1.6.8. 2-{2-[(1H-Indole-2-carbonyl)-amino]-benzoy-
lamino}-3-(4-methoxy-phenyl)-propionic acid ethyl ester
(8f). Trituration with hot MeOH afforded the titled com-
pound in 79% yield. TLC (AcOEt/n-hexane 1:1) - Rf: 0.69;
1
m.p. 189 °C; H-NMR (DMSO-d6) d 1.16 (t, 3H, –CH2–
CH3); 3.13 (m, 2H, –CH2–CH<); 3.62 (s, 3H, –O–CH3); 4.13
(q, 2H, –CH2–O–); 4.74 (m, 1H, –CH<); 6.83 (m, 2H, Ar);
6.98 (s, 1H, Ar); 7.10 (t, 1H, Ar); 7.25 (m, 4H, Ar); 7.49 (d,
1H, Ar); 7.61 (t, 1H, Ar); 7.72 (d, 1H, Ar); 7.82 (d, 1H, Ar);
8.64 (d, 1H, Ar); 9.26 (d, 1H, –NH–CH<); 11.94 (s, 1H,
–NH–); 12.16 (s, 1H, –NH–); 13C-NMR (DMSO-d6) d 13.98,
35.24, 54.58, 54.79, 60.71, 102.54, 112.46, 113.61, 119.35,
119.89, 120.17, 121.73, 122.54, 124.05, 126.92, 128.44,
129.19, 130.05, 131.49, 132.60, 137.11, 139.11, 157.92,
159.07, 168.88, 171.24.
4.1.6.12. 3-(4-Chloro-phenyl)-2-{2-[(1H-indole-2-carbonyl)-
amino]-benzoylamino}-propionic acid ethyl ester (12f). Tritu-
ration with hot MeOH afforded the titled compound in 72%
yield. TLC (AcOEt/n-hexane 1:1) - Rf: 0.65; m.p. 205 °C;
1H-NMR (DMSO-d6) d 1.15 (t, 3H, –CH3); 3.20 (m, 2H,
–CH2–CH<); 4.13 (q, 2H, –CH2–O–); 4.79 (m, 1H, –CH<);
6.98 (s, 1H, Ar); 7.06–7.40 (m, 7H, Ar); 7.49 (d, 1H, Ar);
7.61 (t, 1H, Ar); 7.71 (d, 1H, Ar); 7.80 (d, 1H, Ar); 8.65 (d,
1H,Ar); 9.31 (d, 1H, –NH–CH<); 11.95 (s, 1H, –NH–); 12.16
(s, 1H, –NH–); 13C-NMR (DMSO-d6) d 13.98, 35.34, 54.11,
60.84, 102.55, 112.50, 119.22, 119.93, 120.19, 121.76,
122.57, 124.07, 126.95, 128.14, 128.42, 131.00, 131.29,
131.51, 132.69, 136.48, 137.14, 139.18, 159.11, 168.93,
171.01.
4.1.6.9. 3-(4-Fluoro-phenyl)-2-{2-[(1H-indole-2-carbonyl)-
amino]-benzoylamino}-propionic acid ethyl ester (9f). Tritu-
ration with hot MeOH afforded the titled compound in 68%