6592 Journal of Medicinal Chemistry, 2004, Vol. 47, No. 26
Llina`s-Brunet et al.
1H), 1.30-1.19 (m, 1H), 1.22 (s, 9H), 0.97 (s, 9H). HRMS:
found, 687.3388; calcd for C8H47N4O8, 687.3388. HPLC: (a)
93.5%; (b) 94.4%.
HRMS: found, 701.3178; calcd for C38H45N4O9, 701.3181.
HPLC: (a) 94.7%; (b) 95.1%.
Compound 33. 1H NMR (DMSO-d6): δ 8.60 (s, 1H), 8.35-
8.32 (m, 4H), 7.77 (s, 1H), 7.68 (d, J ) 8.2 Hz, 1H), 7.62-7.54
(m, 3H), 6.68 (d, J ) 8.0 Hz, 1H), 5.79-5.68 (m, 2H), 5.19 (dd,
J ) 1.6, J′ ) 17.2 Hz, 1H), 5.05 (dd, J ) 1.9, J′ ) 10.2 Hz,
1H), 4.49 (dd, J ) 8.0, J′ )8.0, 1H), 4.42 (d, J ) 12.1 Hz, 1H),
4.01(d, J ) 8.3 Hz, 2H), 2.58 (dd, J ) 7.6, J′ ) 15.0 Hz, 1H),
2.33-2.23 (m, 1H), 2.03 (dd, J ) 8.9, J′ ) 17.5 Hz, 1H), 1.56
(dd, J ) 4.8, J′ ) 7.6 Hz, 1H), 1.28 (dd, J ) 5.1, J′ ) 9.2 Hz,
1H), 1.11 (s, 9H), 0.96 (s, 9H). HRMS: found, 725.3160; calcd
for C38H44N4O7F3, 725.3157. HPLC: (a) 96.2%; (b) 93.9%.
Compound 34. 1H NMR (DMSO-d6): δ 8.58 (s, 1H), 8.31-
8.25 (m, 3H), 7.93 (s, 1H), 7.70 (s, 1H), 7.62-7.54 (m, 3H), 7.44
(d, J ) 8.9 Hz, 1H), 6.71 (d, J ) 8.0 Hz, 1H), 5.77-5.67 (m,
2H), 5.18 (d, J ) 1.6, J′ ) 17.2 Hz, 1H), 5.06 (dd, J ) 1.9, J′
) 10.2 Hz, 1H), 4.49-4.43 (m, 2H), 4.03 (d, J ) 8.3 Hz, 1H),
3.93 (d, J ) 9.2 Hz, 1H), 2.57 (dd, J ) 7.0, J′ ) 14.0 Hz, 1H),
2.33-2.21 (m, 1H), 2.02 (dd, J ) 8.9, J′ ) 17.2 Hz, 1H), 1.56
(dd, J ) 5.1, J′ ) 7.6 Hz, 1H), 1.27 (dd, J ) 4.8, J′ ) 9.2 Hz,
1H), 1.15 (s, 9H), 0.96 (s, 9H). HRMS: found, 741.3101; calcd
for C38H44N4O8F3, 741.3106. HPLC: (a) 91.6%; (b) 95.9%.
Compound 35. 1H NMR (DMSO-d6): δ 8.58 (s, 1H), 8.25-
8.14 (m, 3H), 7.71-7.53 (m, 5H), 7.28-7.20 (m, 1H), 7.01 (d,
J ) 8.6 Hz, 1H), 5.80-5.66 (m, 2H), 5.19 (dd, J ) 1.6, J′ )
16.9 Hz, 1H), 5.06 (dd, J ) 1.9, J′ ) 10.5 Hz, 1H), 4.60-4.52
(m, 1H), 4.47 (dd, J ) 7.6, J′ ) 7.6 Hz, 1H), 4.07 (d, J ) 8.6
Hz, 1H), 3.96 (s, 3H), 2.58 (dd, J ) 6.0, J′ ) 13.3 Hz, 1H),
2.34-2.25 (m, 1H), 2.02 (dd, J ) 8.3, J′ ) 17.2 Hz, 1H), 1.70-
1.29 (m, 8H), 1.26 (dd, J ) 5.1, J′ ) 9.5 Hz, 1H), 0.96 (s, 9H).
HRMS: found, 699.3394; calcd for C39H47N4O8, 699.3388.
HPLC: (a) 95.6%; (b) 96.1%.
Compound 26. 1H NMR (DMSO-d6): δ 8.57 (s, 1H), 8.31-
8.18 (m, 3H), 8.15-8.08 (m, 1H), 7.95-7.83 (m, 1H), 7.71 (s,
1H), 7.69-7.54 (m, 4H), 6.75 (d, J ) 8.3 Hz, 1H), 5.82-5.66
(m, 2H), 5.18 (dd, J ) 1.6 Hz, J′ ) 17.2 Hz, 1H), 5.06 (dd, J )
1.9 Hz, J′ )10.2 Hz, 1H), 4.56-4.39 (m, 2H), 4.07 (d, J ) 8.6
Hz, 1H), 4.02-3.91 (m, 1H), 2.64-2.55 (m, 1H), 2.35-2.24 (m,
1H), 2.07-1.97 (m, 1H), 1.59-1.52 (m, 1H), 1.30-1.24 (m, 1H),
1.22 (s, 9H), 0.97 (s, 9H). HRMS: found, 657.3289; calcd for
C37H45N4O7, 657.3283. HPLC: (a) 98.2%; (b) 95.1%.
1
Compound 27. H NMR (DMSO-d6): ca. 1:15 mixture of
rotamers, only major rotamer described; δ 8.59 (s, 1H), 8.22-
8.16 (m, 3H), 7.71-7.62 (m, 4H), 7.52 (s, 1H), 7.21-7.16 (m,
1H), 6.74 (d, J ) 8.6 Hz, 1H), 5.79-5.66 (m, 2H), 5.18 (d, J )
17.2, 1H), 5.05 (d, J ) 10.5, 1H), 4.82 (h, J ) 6.0, 1H), 4.51-
4.43 (m, 1H), 4.02 (d, J ) 8.3 Hz, 1H), 3.97-3.93 (m, 1H),
2.61-2.56 (m, 1H), 2.33-2.24 (m, 1H), 2.06-1.98 (m, 1H), 1.55
(dd, J ) 4.9, J′ ) 7.8 Hz, 1H), 1.38 (d, J ) 6.4 Hz, 6H), 1.29-
1.25 (m, 1H), 1.20 (s, 9H), 0.97 (s, 9H). HRMS: found,
715.3698; calcd for C40H51N4O8, 715.3701. HPLC: (a) 92.3%;
(b) 94.4%.
1
Compound 28. H NMR (DMSO-d6): ca. 1:15 mixture of
rotamers, only major rotamer described; δ 10.62 (s, 1H), 8.84
(s, 1H), 8.57 (s, 1H), 8.28-8.22 (m, 1H), 8.19-8.13 (m, 2H),
7.74-7.59 (m, 5H), 6.81 (d, J ) 8.6 Hz, 1H), 5.82-5.66 (m,
2H), 5.18 (dd, J ) 1.6, J′ ) 17.2 Hz, 1H), 5.05 (dd, J ) 1.9, J′
) 10.2 Hz, 1H), 4.51 (d, J ) 11.2 Hz, 1H), 4.45-4.38 (m, 1H),
4.08-3.92 (m, 2H), 2.61-2.55 (m, 1H), 2.33-2.25 (m, 1H), 2.17
(s, 3H), 2.24-1.96 (m, 1H), 1.55 (dd, J ) 5.1, J′ ) 7.9 Hz, 1H),
1.27 (s, 9H), 1.22-1.26 (m, 1H), 0.98 (s, 9H). HRMS: found,
714.3491; calcd for C39H48N5O8, 714.3497. HPLC: (a) 97.6%;
(b) 95.3%.
Compound 36. 1H NMR (DMSO-d6): ca. 1:6 mixture of
rotamers, only major rotamer described; δ 8.57 (s, 1H), 8.28-
8.14 (m, 3H), 7.74-7.44 (m, 5H), 7.28 (d, J ) 7.3 Hz, 1H), 7.13
(d, J ) 7.6 Hz, 1H), 5.84-5.66 (m, 2H), 5.19 (d, J ) 17.2 Hz,
1H), 5.06 (dd, J ) 1.9, J′ ) 12.1 Hz, 1H), 4.50-4.34 (m, 3H),
4.07-3.90 (m, 2H), 3.98 (s, 3H), 2.64-2.54 (m, 1H), 2.35-2.25
(m, 1H), 2.07-1.94 (m, 3H), 1.88-1.76 (m, 2H), 1.68-1.37 (m,
3H), 1.29-1.22 (m, 1H), 0.96 (s, 9H). HRMS: found, 685.3230;
calcd for C38H45N4O8, 685.3232. HPLC: (a) 97.8%; (b) 96.6%.
Compound 29. 1H NMR (DMSO-d6): ca. 1:8 mixture of
rotamers, only major rotamer described; δ 8.59 (s, 1H), 8.23-
8.19 (m, 2H), 8.13 (d, J ) 9.0 Hz, 1H), 7.84 (s, 1H), 7.68-7.62
(m, 4H), 7.43 (d, J ) 8.6 Hz, 1H), 6.74 (d, J ) 8.0 Hz, 1H),
5.78-5.67 (m, 2H), 5.18 (dd, J ) 1.6, J′ ) 17.1 Hz, 1H), 5.05
(dd, J ) 1.9, J′ ) 10.5 Hz, 1H), 4.50-4.44 (m, 2H), 4.02 (d, J
) 8.3, 1H), 3.93 (d, J ) 9.9, 1H), 2.64 (s, 3H), 2.62-2.55 (m,
1H), 2.33-2.25 (m, 1H), 2.02 (dd, J ) 8.6, J′ ) 17.5 Hz, 1H),
1.55 (dd, J ) 5.1, J′ ) 7.9 Hz, 1H), 1.29-1.25 (m, 1H), 1.19 (s,
9H), 0.96 (s, 9H). HRMS: found, 703.3174; calcd for C38H47-
N4O7S, 703.3160. HPLC: (a) 95.2%; (b) 95.0%.
1
Compound 37. H NMR (DMSO-d6): δ 8.58 (s, 1H), 8.25
(d, J ) 9.2 Hz, 1H), 8.21-8.14 (m, 2H), 7.73-7.53 (m, 5H),
7.27 (d, J ) 9.2 Hz, 1H), 5.99-5.86 (m, 2H), 5.80-5.67 (m,
2H), 5.20 (dd, J ) 1.6, J′ ) 17.2 Hz, 1H), 5.07 (dd, J ) 1.9, J′
) 10.2 Hz, 1H), 4.58 (d, J ) 11.8 Hz, 1H), 4.44 (dd, J ) 9.2, J′
)9.2 Hz, 1H), 4.15 (d, J ) 8.6 Hz, 1H), 3.98 (s, 3H), 3.37-3.27
(m, 1H), 3.01 (bs, 1H), 2.68-2.55 (m, 1H), 2.36-2.26 (m, 1H),
2.03 (dd, J ) 8.9, J′ ) 17.5 Hz, 1H), 1.78-1.38 (m, 10H), 1.30-
0.99 (m, 13 H), 0.94 (s, 9H). HRMS: found, 712.3716; calcd
for C40H50N5O7, 712.3705. HPLC: (a) 95.3%; (b) 95.6%.
Compound 38. 1H NMR (DMSO-d6): ca. 1:6 mixture of
rotamers, only major rotamer described; δ 8.58 (s, 1H), 8.35-
8.10 (m, 3H), 7.75-7.60 (m, 4H), 7.60-7.45 (m, 1H), 7.25-
7.15 (m, 1H), 5.99 (d, J ) 6.4 Hz, 1H), 5.90 (d, J ) 9.0 Hz,
1H), 5.80-5.65 (m, 2H), 5.19 (d, J ) 17.0 Hz, 1H), 5.06 (d, J
) 10.4 Hz, 1H), 4.56 (d, J ) 11.6 Hz, 1H), 4.42 (dd, J ) 8.8, J′
) 8.8 Hz, 1H), 4.20-4.10 (m, 2H), 4.05-3.95 (m, 1H), 3.96 (s,
3H), 2.64-2.54 (m, 1H), 2.35-2.25 (m, 1H), 2.07-1.97 (m, 1H),
1.78-1.34 (m, 7H), 1.28-1.20 (m, 1H), 1.19-1.06 (m, 1H),
1.05-0.96 (m, 1H), 0.93 (s, 9H). HRMS: found, 698.3545; calcd
for C39H48N5O7, 698.3548. HPLC: (a) 99.0%; (b) 95.8%.
Compound 30. 1H NMR (DMSO-d6): ca. 1:6 mixture of
rotamers, only major rotamer described; δ 8.57 (s, 1H), 8.29-
8.23 (m, 3H), 7.75 (dd, J ) 2.2 Hz, J′ ) 10.2 Hz, 1H), 7.65-
7.55 (m, 4H), 7.39-7.33 (m, 1H), 6.71 (d, J ) 8.0 Hz, 1H),
5.76-5.66 (m, 2H), 5.18 (d, J ) 17.2, 1H), 5.05 (d, J ) 10.5,
1H), 4.48-4.40 (m, 2H), 4.08-3.92 (m, 2H), 2.59-2.52 (m, 1H),
2.33-2.23 (m, 1H), 2.06-1.98 (m, 1H), 1.55 (dd, J ) 4.9, J′ )
7.8 Hz, 1H), 1.29-1.25 (m, 1H), 1.21 (s, 9H), 0.97 (s, 9H).
HRMS: found, 675.3180; calcd for C37H44N4O7F, 675.3189.
HPLC: (a) 95.9%; (b) 93.8%.
1
Compound 31. H NMR (DMSO-d6): ca. 1:12 mixture of
rotamers, only major rotamer described; δ 8.58 (s, 1H), 8.29-
8.25 (m, 2H), 8.23-8.19 (m, 1H), 8.09 (d, J ) 8.9 Hz, 1H), 7.67
(s, 1H), 7.63-7.55 (m, 3H), 6.69 (d, J ) 8.0 Hz, 1H), 5.76-
5.66 (m, 2H), 5.22 (d, J ) 15.6, 1H), 5.05 (d, J ) 10.2, 1H),
4.48-4.39 (m, 2H), 4.02 (d, J ) 8.6, 1H), 3.89-3.94 (m, 1H),
2.58-2.55 (m, 1H), 2.33-2.23 (m, 1H), 2.06-1.98 (m, 1H), 1.55
(dd, J ) 4.9, J′ ) 7.8 Hz, 1H), 1.29-1.25 (m, 1H), 1.18 (s, 9H),
0.96 (s, 9H). HRMS: found, 735.2395; calcd for C37H44N4O7-
Br, 735.2388. HPLC: (a) 89.6%; (b) 94.1%.
1
Compound 39. H NMR (DMSO-d6): δ 8.59 (s, 1H), 8,24
(d, J ) 9.2 Hz, 1H), 8.20-8.13 (m, 2H), 7.71-7.51 (m, 6H),
7.23 (d, J ) 9.2 Hz, 1H), 5.98-5.84 (m, 2H), 5.79-5.68 (m,
2H), 5.18 (d, J ) 17.2 Hz, 1H), 5.06 (d, J ) 10.2 Hz, 1H), 4.58
(d, J ) 11.8 Hz, 1H), 4.42 (dd, J ) 9.2, J′ ) 9.2 Hz, 1H), 4.12
(d, J ) 6.7 Hz, 1H), 3.97 (s, 3H), 2.58 (dd, J ) 7.0, J′ ) 13.3
Hz, 1H), 2.36-2.24 (m, 1H), 2.03 (dd, J ) 8.9, J′ ) 17.4 Hz,
1H), 1.56 (dd, J ) 5.1, J′ ) 7.6 Hz, 1H), 1.28-1.21 (m, 1H),
1.05 (s, 9H), 0.95 (s, 9H). HRMS: found, 686.3541; calcd for
C38H48N5O7, 686.3548. HPLC: (a) 93.2%; (b) 89.1%.
1
Compound 32. H NMR (DMSO-d6): ca. 1:10 mixture of
rotamers, only major rotamer described; δ 8.61-8.56 (m, 2H),
8.33-8.27 (m, 3H), 7.97 (d, J ) 8.3 Hz, 1H), 7.75 (s, 1H), 7.65-
7.57 (m, 3H), 6.73 (d, J ) 8.3 Hz, 1H), 5.79-5.66 (m, 2H), 5.18
(d, J ) 17.2, 1H), 5.05 (d, J ) 10.5, 1H), 4.49-4.43 (m, 2H),
4.06 (d, J ) 8.3 Hz, 1H), 3.97-3.93 (m, 1H), 2.61-2.56 (m,
1H), 2.33-2.24 (m, 1H), 2.06-1.98 (m, 1H), 1.55 (dd, J ) 4.9,
J′ ) 7.8 Hz, 1H), 1.29-1.25 (m, 1H), 1.20 (s, 9H), 0.97 (s, 9H).
Compound 40. 1H NMR (DMSO-d6): δ 12.41 (bs, 1H), 8.56
(s, 1H), 8.50-8.04 (m, 1H), 8.23 (bs, 2H), 7.90-7.35 (m, 5H),