C. Martins et al. / Bioorg. Med. Chem. Lett. 17 (2007) 2293–2298
2297
The favourable DTm and telEC50 values for compound 2
compared to 1 (BRACO-19), together with its improved
lipophilicity and pharmacokinetic behaviour (to be pub-
lished), have led to the selection of 2 as a potential clin-
ical candidate molecule. In vivo antitumour data for 2
will be reported elsewhere, but off-target toxicity has
been more recently observed, and further compounds
with diminished toxicity are now being evaluated.
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Acknowledgments
´
Macadre, J.; Koebel, P.; Giraud-Panis, M.-J.; Kaplan, H.;
We are grateful to Cancer Research UK and Antisoma
Ltd for support of these studies.
Kolkes, A.; Shin-ya, K.; Riou, J.-F. Cancer Res. 2006, 66,
6908.
17. Gunaratnam, M.; Riou, J. F.; Neidle, S. et al., to be
published.
Supplementary data
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26. Compound 2: dH (400 MHz, CDCL3) 1.85 (br s, 8H), 2.50
(t, 5.6 Hz, 4H), 2.63 (br s, 8H), 2.80 (t, 5.6 Hz, 4H), 4.81 (s,
2H), 7.04 (m, 2H), 7.19 (m, 1H), 7.87–7.89 (m, 6H), 11.50
(s, 2H); m/z 602 (MH+); C34H38N6O2F2 requires 601.3097;
observed 601.3080. Compound 3: dH (400 MHz, MeOD)
1.86 (s (br), 8H), 2.51 (t, 5.6 Hz, 4H), 2.64 (br s, 8H), 2.81
(t, 5.6 Hz, 4H), 3.68 (s, 6H), 4.80 (s, 2H), 6.34 (m, 1H),
6.46 (m, 2H), 7.07 (m, 2H), 7.82 (m, 2H), 7.91 (d, 9.2 Hz,
2H), 11.52 (s, 2H); m/z 625 (MH+); C36H44N6O4 requires
625.3497; observed 625.3500. Compound 4: dH (400 MHz,
CDCL3) 1.92 (br s, 8H), 2.35 (s, 3H), 2.57 (t, 5.6 Hz,
4H),2,69 (br s, 8H), 2.87 (t, 5.6 Hz, 4H), 4.89 (s, 2H), 7.13–
7.20 (m, 3H), 7.24–7.28 (m, 1H), 7.74 (m, 2H), 7.88 (br s,
2H), 7.99 (d, 9.2 Hz, 2H) 11.50 (s, 2H); m/z 579 (MH+);
C35H42N6O2 requires 579.3442; observed 579.3464. Com-
pound 5: dH (400 MHz, CDCL3) 1.94 (s (br), 8H), 2.58 (t,
5.6 Hz, 4H), 2.72 (br s, 8H), 2.88 (t, 5.6 Hz, 4H), 5.03 (s,
2H), 7.43–7.96 (m, 9H), 11.63 (s, 2H); m/z 651 (MH+);
C35H38N6O2F4 requires 651.3065; observed 651.3049.
Compound 6: dH (400 MHz, CDCL3) 1.94 (s, 8H), 2.58
(t, 5.6 Hz, 4H), 2.71 (s, 8H), 2.88 (t, 5.6 Hz, 4H), 5.12 (s,
2H), 7.82–7.99 (m, 9H), 11.65 (s, 2H); m/z 701 (MH+);
C36H38N6O2F6 requires 701.3033; observed 701.3034.
Compound7: dH (400 MHz, CDCL3) 1.50 (br s, 4H),
1.66 (br s, 8H), 2.52 (br s, 12H), 2.66 (m, 4H), 2.93 (s, 6H),
4.93 (s, 2H), 6.84 (d, J = 8.4 Hz 1H), 7.11 (m, 2H), 7.27
(m, 1H), 7.85 (br s, 2H), 7.88–7.98 (m, 3H), 8.32 (m, 1H),
11.66 (s, 2H); m/z 629 (MH+); C36H42N6O2F2 requires
629.3410; observed 629.3429. Compound 8: dH (400 MHz,
CDCL3) 1.46 (s (br), 4H), 1.65 (br s, 8H), 2.53 (m, 12H),
2.66 (m, 4H), 3.73 (s, 6H), 4.88 (s, 2H), 5.69 (br s, 1H),
6.40 (br s, 1H), 6.55 (br s, 2H), 7.82–8.06 (m, 6H) 11.65 (s,
2H); m/z 654 (MH+); C38H48N6O4 requires 653.3810;
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