New Class of Fibrinogen Receptor Antagonists
J ournal of Medicinal Chemistry, 1998, Vol. 41, No. 14 2501
4-(4-P ip er id in yl)b u t a n oyl-N-et h ylglycyl-a sp a r t yl-cy-
cloh exyla la n in e (7). NMR (D2O): δ 4.52 (m, 1H), 4.30 (m,
1H), 4.05 (s, 1H), 3.88 (s, 1H), 3.32 (q, J ) 8.6 Hz, 2H), 3.20
(m, 2H), 2.72 (m, 5H), 2.33 (t, J ) 8.6 Hz, 2H), 2.10 (m, 1H),
1.75 (m, 2H), 1.50 (m, 10H), 1.18 (m, 4H), 1.00 (m, 3H), 0.70
(m, 6H). MS: m/z (FAB) 525 (M + H)+. HPLC: tR 18.63 min,
99.9 A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-(S)-
2-a m in o-5-cycloh exylp en ta n oic Acid (18). NMR (D2O): δ
4.65 (m, 1H), 4.23 (m, 1H), 4.10 (s, 1H), 3.95 (s, 1H), 3.35 (q,
J ) 6.0 Hz, 2H), 3.27 (m, 2H), 2.75 (m, 4H), 2.40 (t, J ) 7.2
Hz, 1H), 2.15 (t, J ) 7.2 Hz, 1H), 1.82 (m, 3H), 1.60 (m, 12H),
1.25 (m, 6H), 1.00 (m, 3H), 0.72 (m, 4H). MS: m/z (FAB) 553
(M + H)+. HPLC: tR 19.62 min, 99.9 A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-â-cy-
clop en tyla la n in e (19). NMR (D2O): δ 4.75 (m, 1H), 4.30 (m,
1H), 4.15 (q, J ) 12.7, 8.6 Hz, 2H), 3.50 (m, 5H), 2.85 (t, J )
17.1 Hz, 2H), 2.75 (m, 3H), 2.52 (t, J ) 8.5 Hz, 2H), 2.35 (t, J
) 8.5 Hz, 1H), 1.95 (d, J ) 8.5 Hz, 2H), 1.55 (m, 13H), 1.12
(m, 3H). MS: m/z (FAB) 511 (M + H)+. HPLC: tR 17.82 min,
99.8 A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-n or -
leu cin e (8). NMR (D2O): δ 4.54 (m, 1H), 4.15 (m, 1H), 4.04
(s, 1H), 3.85 (s, 1H), 3.32 (q, J ) 7.9 Hz, 2H), 3.17 (m, 2H),
2.70 (m, 4H), 2.30 (t, J ) 7.7 Hz, 2H), 2.09 (t, J ) 8.2 Hz, 1H),
1.65 (m, 4H), 1.40 (m, 2H), 1.15 (m, 8H), 0.98 (m, 3H), 0.68
(m, 3H). MS: m/z (FAB) 485 (M + H)+. HPLC: tR 13.19 min,
99.9A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-â-cy-
cloh ep tyla la n in e (20). NMR (D2O): δ 4.57 (m, 1H), 4.30 (m,
1H), 4.08 (s, 1H), 3.92 (s, 1H), 3.35 (q, J ) 7.2 Hz, 2H), 3.26
(m, 2H), 2.75 (m, 4H), 2.35 (t, J ) 7.2 Hz, 1H), 2.18 (m, 1H),
1.82 (m, 2H), 1.40 (m, 21H), 1.00 (m, 3H). MS: m/z (FAB)
539 (M + H)+. HPLC: tR 17.21 min, 98.9 A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-ter t-
bu tylglycin e (9). NMR (D2O): δ 4.60 (m, 1H), 4.25 (m, 1H),
3.88 (s, 2H), 3.33 (q, J ) 7.8 Hz, 2H), 3.20 (m, 2H), 2.74 (m,
4H), 2.35 (t, J ) 7.6 Hz, 2H), 2.12 (t, J ) 8.1 Hz, 1H), 1.80 (m,
2H), 1.50 (m, 4H), 1.15 (m, 4H), 1.03 (m, 3H), 0.78 (s, 9H).
MS: m/z (FAB) 499 (M + H)+. HPLC: tR 13.94 min, 99.2 A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-â-cy-
clooctyla la n in e (21). NMR (D2O): δ 4.40 (m, 1H), 4.20 (q,
J ) 8.6, 8.6 Hz, 2H), 3.95 (m, 2H), 3.30 (m, 4H), 2.82 (m, 4H),
2.35 (t, J ) 9.1 Hz, 2H), 2.12 (t, J ) 8.6 Hz, 1H), 1.85 (d, J )
8.6 Hz, 2H), 1.57 (m, 14H), 1.35 (m, 5H), 1.10 (m, 12H). MS:
m/z (FAB) 553 (M + H)+. HPLC: tR 22.30 min, 99.5 A%.
4-(4-P ip er id in yl)b u t a n oyl-N-et h ylglycyl-a sp a r t yl-cy-
cloh exyla la n in e Eth yl Ester (22). NMR (D2O): δ 4.45 (m,
1H), 4.18 (q, J ) 12.4, 8.6 Hz, 2H), 3.95 (m, 2H), 3.30 (m, 5H),
2.87 (m, 5H), 2.35 (t, J ) 8.6 Hz, 2H), 2.25 (t, J ) 8.6 Hz, 1H),
1.89 (m, 2H), 1.55 (m, 7H), 1.00 (m, 18H). MS: m/z (FAB)
553 (M + H)+. HPLC: tR 17.04 min, 98.3 A%.
4-(4-P ip er id in yl)b u t a n oyl-N-et h ylglycyl-a sp a r t yl-cy-
cloh exyla la n in a m id e (23). NMR (D2O): δ 4.43 (m, 1H), 4.20
(m, 1H), 4.08 (s, 1H), 3.92 (d, J ) 2.2 Hz, 1H), 3.35 (q, J ) 6.0
Hz, 2H), 3.25 (m, 2H), 2.83 (dt, J ) 8.6, 2.4 Hz, 2H), 2.52 (m,
2H), 2.36 (t, J ) 6.8 Hz, 2H), 2.14 (m, 1H), 1.80 (m, 2H), 1.50
(m, 10H), 1.21 (m, 4H), 1.00 (m, 3H), 0.75 (m, 5H). MS: m/z
(FAB) 524 (M + H)+. HPLC: tR 16.15 min, 99.4 A%.
4-(4-P ip er id in yl)b u t a n oyl-N-et h ylglycyl-a sp a r t yl-cy-
cloh exyla la n in ol (24). NMR (D2O): δ 4.55 (m, 1H), 4.04 (s,
1H), 3.90 (s, 1H), 3.80 (m, 1H), 3.30 (m, 6H), 2.75 (m, 4H),
2.35 (t, J ) 7.2 Hz, 1H), 2.04 (m, 1H), 1.81 (m, 2H), 1.50 (m,
8H), 1.20 (m, 6H), 0.85 (m, 8H). MS: m/z (FAB) 511 (M +
H)+. HPLC: tR 16.51 min, 98.2 A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-â-(1-
n a p h th yl)a la n in e (10). NMR (D2O): δ 7.95 (d, J ) 9.6 Hz,
1H), 7.80 (m, 1H), 7.65 (m, 1H), 7.42 (m, 2H), 7.26 (m, 1H),
7.22 (t, J ) 9.6 Hz, 1H), 4.52 (m, 2H), 3.78 (s, 1H), 3.71 (s,
1H), 3.57 (m, 2H), 3.20 (m, 4H), 2.55 (m, 4H), 2.21 (t, J ) 8.4
Hz, 2H), 1.78 (t, J ) 7.2 Hz, 1H), 1.58 (m, 2H), 1.20 (m, 6H),
0.92 (m, 3H). MS: m/z (FAB) 569 (M + H)+. HPLC: tR 18.25
min, 99.3 A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-â-(2-
n a p h th yl)a la n in e (11). NMR (D2O): δ 7.55 (m, 3H), 7.42
(s, 1H), 7.20 (m, 2H), 7.10 (d, J ) 9.6 Hz, 1H), 4.52 (m, 2H),
3.57 (d, J ) 6.0 Hz, 1H), 3.41 (s, 1H), 3.10 (m, 3H), 2.85 (m,
3H), 2.53 (m, 4H), 1.98 (t, J ) 8.4 Hz, 2H), 1.54 (m, 3H), 1.10
(m, 6H), 0.71 (t, J ) 6.0 Hz, 3H). MS: m/z (FAB) 569 (M +
H)+. HPLC: tR 18.47 min, 95.5 A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-â-(1-
d eca lin yl)a la n in e (12). NMR (D2O): δ 4.22 (m, 1H), 4.10
(q, J ) 12.4, 8.6 Hz, 2H), 3.40 (m, 4H), 2.77 (m, 4H), 2.35 (t,
J ) 8.6 Hz, 2H), 2.15 (t, J ) 8.6 Hz, 1H), 1.87 (m, 3H), 1.50
(m, 12H), 1.30 (m, 12H), 0.98 (m, 9H). MS: m/z (FAB) 579
(M + H)+. HPLC: tR 25.00 min, 99.4 A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-â-(2-
d eca lin yl)a la n in e (13). NMR (D2O): δ 4.75 (m, 1H), 4.38
(m, 1H), 4.10 (q, J ) 12.4, 8.5 Hz, 2H), 3.55 (m, 5H), 2.77 (m,
5H), 2.55 (t, J ) 8.6 Hz, 2H), 2.30 (t, J ) 8.5 Hz, 1H), 1.95 (d,
J ) 12.4 Hz, 2H), 1.55 (m, 14H), 1.15 (m, 14H), 0.72 (m, 3H).
MS: m/z (FAB) 579 (M + H)+. HPLC: tR 18.00 min, 99.6 A%.
4-(4-P ip er id in yl)b u t a n oyl-N-et h ylglycyl-a sp a r t yl-(2-
cycloh exyl)eth yla m in e (25). NMR (D2O): δ 4.10 (s, 1H),
3.90 (q, J ) 12.4, 12.4 Hz, 2H), 3.35 (d, J ) 8.5 Hz, 2H), 3.25
(d, J ) 12.8 Hz, 2H), 2.73 (m, 8H), 2.35 (t, J ) 12.8 Hz, 2H),
2.15 (t, J ) 17.1 Hz, 2H), 1.83 (m, 4H), 1.57 (m, 7H), 1.10 (m,
12H), 0.75 (t, J ) 21.4 Hz, 2H). MS: m/z (FAB) 481 (M +
H)+. HPLC: tR 17.71 min, 99.3 A%.
4-(4-P ip er id in yl)b u t a n oyl-N-et h ylglycyl-a sp a r t yl-1-
a m in ocycloh exa n e-1-ca r boxylic Acid (14). NMR (D2O):
δ 4.58 (m, 1H), 4.05 (s, 1H), 3.90 (s, 1H), 3.30 (q, J ) 9.0 Hz,
2H), 3.20 (m, 2H), 2.70 (m, 4H), 2.35 (t, J ) 7.2 Hz, 1H), 2.11
(t, J ) 7.2 Hz, 1H), 1.80 (m, 4H), 1.60 (m, 2H), 1.40 (m, 6H),
1.13 (m, 7H), 1.40 (m, 3H). MS: m/z (FAB) 497 (M + H)+.
HPLC: tR 12.53 min, 99.9 A%.
Refer en ces
(1) SCRIP 1995, 2024/25, 23.
(2) Phillips, D. R.; Charo, I. F.; Parise, L. V.; Fitzgerald, L. A. The
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4-(4-P ip er id in yl)b u t a n oyl-N-et h ylglycyl-a sp a r t yl-cy-
cloh exylglycin e (15). NMR (D2O): δ 4.60 (m, 1H), 4.06 (m,
1H), 4.01 (s, 1H), 3.85 (s, 1H), 3.30 (q, J ) 6.0 Hz, 2H), 3.16
(m, 2H), 2.70 (m, 4H), 2.30 (t, J ) 7.2 Hz, 2H), 2.10 (t, J ) 7.2
Hz, 1H), 1.70 (m, 2H), 1.45 (m, 8H), 1.00 (m, 12H). MS: m/z
(FAB) 511 (M + H)+. HPLC: tR 14.81 min, 99.9 A%.
4-(4-P ip er id in yl)bu ta n oyl-N-eth ylglycyl-a sp a r tyl-D-cy-
cloh exyla la n in e (16). NMR (D2O): δ 4.58 (m, 1H), 4.26 (m,
1H), 4.05 (s, 1H), 3.85 (s, 1H), 3.32 (q, J ) 8.4 Hz, 2H), 3.18
(m, 2H), 2.72 (m, 4H), 2.32 (t, J ) 7.2 Hz, 2H), 2.12 (t, J ) 7.2
Hz, 1H), 1.77 (m, 2H), 1.45 (m, 10H), 0.90 (m, 12H). MS: m/z
(FAB) 525 (M + H)+. HPLC: tR 16.94 min, 99.8 A%.
4-(4-P ip er id in yl)bu t a n oyl-N-et h ylglycyl-a sp a r t yl-h o-
m ocycloh exyla la n in e (17). NMR (D2O): δ 4.57 (m, 1H),
4.06 (s, 1H), 4.03 (m, 1H), 3.85 (s, 1H), 3.29 (q, J ) 6.0 Hz,
2H), 3.20 (m, 2H), 2.82 (t, J ) 15.6 Hz, 2H), 2.70 (m, 2H), 2.29
(t, J ) 7.2 Hz, 2H), 2.13 (t, J ) 7.2 Hz, 1H), 1.72 (m, 3H), 1.50
(m, 10H), 1.10 (m, 6H), 1.00 (m, 3H), 0.60 (m, 4H). MS: m/z
(FAB) 539 (M + H)+. HPLC: tR 19.50 min, 99.9 A%.
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