3938
J.-Q. Wang et al. / Bioorg. Med. Chem. Lett. 13 (2003) 3933–3938
Thaler, H.; Conti, P. S.; Blasberg, R. G. J. Nucl. Med. 2002,
43, 1072.
35. Wu, J. C.; Inubushi, M.; Sundaresan, G.; Schelbert, H. R.;
Gambhir, S. S. Circulation 2002, 106, 180.
36. Yaghoubi, S.; Barrio, J. R.; Dahlbom, M.; Iyer, M.;
Namavari, M.; Satyamurthy, N.; Goldman, R.; Herschman,
H. R.; Phelps, M. E.; Gambhir, S. S. J. Nucl. Med. 2001, 42,
1225.
NH), 6.66–7.32 (m, 43H, Ph and 8-CH), 3.72 (s, 6H, 9-OCH3),
3.59 (s, 3H, 2-OCH3), 3.24 (t, 2H, 10-H, J=6.62 Hz), 2.78–2.92
(m, 4H, 40-H), 1.52–1.65 (m, 1H, 30-H), 1.08–1.20 (m, 2H, 20-
H). The analysis calculated for C70H63N5O6 was C, 78.55; H,
5.93. The values found were C, 77.56; H, 5.92. LRMS (EI,
m/z) 273 (100%), 1092 [(M+Na)+, 3.9%). HRMS (FAB,
m/z) calcd for C70H63N5NaO6 1092.4676, found 1092.4684.
9b, mp, 95 ꢁC (dec.), Rf 0. 36 (1% MeOH/CH2Cl2). H NMR
1
37. Yaghoubi, S. S.; Wu, L.; Liang, Q.; Toyokuni, T.; Barrio,
J. R.; Namavari, M.; Satyamurthy, N.; Phelps, M. E.;
Herschman, H. R.; Gambhir, S. S. Gene Ther. 2001, 8, 1072.
38. Zheng, Q.-H.; Liu, X.; Fei, X.; Wang, J.-Q.; Mock, B. H.;
Glick-Wilson, B. E.; Sullivan, M. L.; Hutchins, G. D. Bioorg.
Med. Chem. Lett. 2003, 13, 1787.
39. Mulholland, K. M.; Zheng, Q.-H.; Mock, B. H.; Vavrek,
M. T. J. Labelled Cpd. Radiopharm. 1999, 42 (Suppl. 1), S459.
40. Mock, B. H.; Winkle, W.; Vavrek, M. T. Nucl. Med. Biol.
1997, 24, 193.
(300 MHz, DMSO-d6) d 6.56–8.27 (m, 38H, Ph and 8-CH),
5.11 (dd, 2H, 10-CH2, J1=44.85 Hz, J2=11.03 Hz), 3.73 (s,
3H, OCH3), 3.53 (s, 3H, OCH3), 3.38–3.57 (m, 3H, 30-CH and
40-CH2), 2.30–2.71 (m, 2H, 50-CH2), 2.41 (s, 6H, CH3). LRMS
(EI, m/z) 273 (100%), 1108 [(M+H)+, 1.4%]. HRMS (FAB,
m/z) calcd for C63H58N5O10S2 1108.3625, found 1108.3667. 9c,
1
Rf 0. 29 (4% MeOH/CH2Cl2). H NMR (300 MHz, CDCl3) d
11.63 (brs, 1H, 1-NH, D2O exchangeable), 7.87 (brs, 1H, 2-
NH, D2O exchangeable), 7.75 (d, 2H, Ph, J=7.36 Hz), 6.87–
7.45 (m, 27H, Ph and 8-H), 6.81 (d, 2H, Ph, J=8.09 Hz), 6.61
(d, 2H, Ph, J=8.09 Hz), 3.75–4.05 (m, 2H, 40-CH2OTs), 3.76
(s, 3H, 9-OCH3), 3.62 (s, 3H, 2-OCH3), 3.15–3.35 (m, 2H, 10-
H), 2.76–3.04 (m, 2H, 50-CH2OTrM), 2.41 (s, 3H, CH3), 1.51
(brs, 1H, 30-H), 1.26 (br. s, 2H, 20-H). 9d, mp 95–98 ꢁC, Rf 0.35
41. Singh, D.; Wani, M. J.; Kumar, A. J. Org. Chem. 1999,
64, 4665.
42. Gao, H.; Mitra, A. K. Synthesis 2000, 3, 329.
43. 6b, Rf 0. 29 (9:1 EtOAc/MeOH). 1H NMR (300 MHz,
DMSO-d6) d 10.92 (s, 1H, 1-NH), 8.11 (s, 1H, 8-CH), 7.10–
7.40 (m, 10H, Ph), 6.24 (s, 2H, 2-NH2), 5.68 (s, 2H, 10-CH2),
4.40 (s, 4H, PhCH2), 4.10 (q, 1H, 30-CH, J=4.78 Hz), 3.30–
3.60 (m, 4H, 40-CH2). LRMS (EI, m/z) 91 (100%), 436
[(M+H)+, 0.4%]. HRMS (FAB, m/z) calcd for C23H26N5O4
436.4838, found 436.1993. 6d, mp 130 ꢁC (dec.), Rf 0.32
(EtOAc). 1H NMR (300 MHz, DMSO-d6) d 8.08 (s, 1H, 8-H),
6.91 (s, 2H, 2-NH2), 3.30–4.10 (m, 6H, 10- and 40-H), 2.12–2.30
(m, 2H, 20-H), 1.35–1.52 (m, 1H, 30-H), 1.24 (s, 3H, CH3), 1.19
(s, 3H, CH3). The analysis calculated for C13H18ClN5O2 was
C, 50.08; H, 5.82. The values found were C, 50.13; H, 5.83.
LRMS (EI, m/z): 154 (100%), 312 [(M+H)+, 13.9%]. HRMS
(FAB, m/z) calcd for C13H19ClN5O2 312.1227, found
312.1234. 8b, mp 115 ꢁC (dec.), Rf 0.34 (5% MeOH/CH2Cl2).
1H NMR (300 MHz, DMSO-d6) d 10.68 (s, 1H, 1-NH), 7.84
(s, 1H, 8-CH), 7.67 (s, 1H, 2-NH), 6.53–7.36 (m, 42H, Ph),
4.91 (s, 2H, 10-CH2), 3.75 (s, 6H, OCH3), 3.57–3.67 (m, 1H, 30-
CH), 3.48 (s, 3H, OCH3), 2.63 (brs, 4H, 40-CH2). LRMS (EI,
m/z) 273 (100%), 1094 [(M+Na)+, 1.6%]. HRMS (FAB, m/z)
calcd for C69H61NaN5O7 1094.4469, found 1094.4452. 8d, mp
145 ꢁC (dec.), Rf 0.26 (4% MeOH/CH2Cl2). 1H NMR
(300 MHz, DMSO-d6) d 10.48 (s, 1H, 1-NH), 7.55 (s, 1H, 2-
1
(4% MeOH/CH2Cl2). H NMR (300 MHz, CDCl3) d 7.96 (d,
2H, Ph, J=7.35 Hz), 7.74 (d, 2H, Ph, J=8.09 Hz), 6.95–7.45
(m, 29H, Ph and 2-NH), 6.80 (d, 2H, Ph, J=8.09 Hz), 6.70 (d,
2H, Ph, J=8.82 Hz), 6.37 (s, 1H, 8-CH), 3.78–4.03 (m, 2H, 40-
CH2OTs), 3.77 (s, 3H, 9-OCH3), 3.72 (s, 3H, 2-OCH3), 3.28–
3.47 (m, 2H, 10-CH2), 2.80–3.04 (m, 2H, 50-CH2OTrM), 2.42
(s, 6H, CH3), 1.45 (brs, 1H, 30-CH), 1.20–1.38 (m, 2H, 20-
CH2). The analysis calculated for C64H59N5O9S2: C, 69.48; H,
5.38. The values found were C, 68.88; H, 5.40. LRMS (EI,
m/z) 273 (100%), 1106 [(M+H)+, 2.6%]. HRMS (FAB, m/z)
calcd for C64H60N5O9S2 1106.3833, found 1106.3861. 1a, Rf
0.34 (12:1 MeCN/H2O). 1H NMR (300 MHz, DMSO-d6) d
10.89 (s, 1H, 1-NH, D2O exchangeable), 7.81 (s, 1H, 8-CH),
6.78 (s, 2H, 2-NH2, D2O exchangeable), 5.42 (s, 2H, 10-CH2),
4.93 (t, 1H, OH, J=5.88 Hz, D2O exchangeable), 4.24–4.58
(m, 2H, 40-CH2F), 3.73–3.88 (m, 1H, 30-CH), 3.28–3.43 (m,
2H, 50-CH2). 1b, Rf 0.19 (4:1 MeCN/H2O). 1H NMR
(300 MHz, DMSO-d6) d 7.53 (s, 1H, 8-CH), 6.74 (s, 2H, 2-
NH2, D2O exchangeable), 5.06 (brs, 1H, OH, D2O exchange-
able), 4.30 (brs, 2H, 10-CH2), 4.13 (dd, 2H, 40-CH2, J=47.06
Hz), 3.35 (d, 2H, 50-CH2, J=52.94 Hz), 2.05–2.32 (m, 2H, 20-
CH2), 1.59–1.74 (m, 1H, 30-CH).