A. S. Kiselyov et al. / Bioorg. Med. Chem. Lett. 16 (2006) 1440–1444
1443
(d, J = 7.4 Hz, 2H), 4.61 (br s, exch. D2O, 1H, NH), 5.06
(br s, exch. D2O, 1H, NH), 6.88 (d, J = 8.0 Hz, 2H), 7.12
(d, J = 8.0 Hz, 2H), 7. 55 (d, J = 8.4 Hz, 2H), 8.56 (d,
J = 8.4 Hz, 2H), 8.92 (s, 1H); 13C NMR (100 MHz,
DMSO-d6) d, ppm: 27.8, 45.7, 116.5, 123.7, 124.3, 125.9,
127.4, 128.2, 129.6, 133.2, 138.1, 142.0, 146.8, 150.2; ESI
MS (M+1): 383, (MÀ1): 381; HRMS, exact mass calcd for
C18H16ClN7O: 381.1105, found: 381.1093. Elemental
analysis: calcd for C18H16ClN7O: C, 56.62; H, 4.22; N,
25.68. Found: C, 56.41; H, 4.35, N, 25.54.Compound 8:
5-(4-(benzo[d][1,3]dioxol-5-ylmethylamino)-1-methyl-
1H-imidazol-5-yl)-N-(4-chloro phenyl)-1,3,4-oxadiazol-
2-amine; mp 196–198 ꢁC; 1H NMR (400 MHz, DMSO-
d6) d, ppm: 3.59 (s, 3H), 4.13 (d, J = 7.4 Hz, 2H), 4.68 (br
s, exch. D2O, 1H, NH), 5.12 (br s, exch. D2O, 1H, NH),
5.88 (s, 2H), 6.53 (m, 2H), 6.62 (d, J = 6.8 Hz, 1H), 6.84
(d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.0 Hz, 2H), 8.91 (s, 1H);
13C NMR (100 MHz, DMSO-d6) d, ppm: 28.1, 46.0, 101.4,
111.6, 114.9, 117.0, 120.1, 123.3, 124.5, 125.9, 126.7, 127.1,
129.3, 135.2, 138.4, 141.0, 146.2, 148.3; ESI MS (M+1):
426, (MÀ1): 424; HRMS, exact mass calcd for
C20H17ClN6O3: 424.1051, found: 424.1043. Elemental
analysis: calcd for C20H17ClN6O3: C, 56.54; H, 4.03; N,
19.78. Found: C, 56.31; H, 3.88, N, 19.56.
In summary, we have described a series of novel imidaz-
ole derivatives as potent inhibitors of the VEGFR-2
receptor in both in vitro and cell-based assays
(IC50 < 100 nM). By controlling the substitution pattern
on the anilinic portion of the molecule, both dual and
specific VEGFR-2 imidazoles were identified. The ana-
logues presented in this Letter are potentially useful in
the treatment of conditions such as cancer. Further de-
tails on their biological properties, such as functional
activity, together with murine oral exposure data will
be presented in due course.
References and notes
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containing 100 mM EDTA and 0.36 lg/ml PY20K (Eu-
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medium and incubated at room temperature for 30 min
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9. Analytical data for selected compounds. Compound 5: N-
(4-chlorophenyl)-5-(1-methyl-4-(pyridin-4-ylmethylamino)-
1H-imidazol-5-yl)-1,3,4-oxadiazol-2-amine; mp 229–231 ꢁC;
1H NMR (400 MHz, DMSO-d6) d, ppm: 3.55 (s, 3H), 4.25