Patent ID: 6239104
Filing Date: 2001-05-29
Classification: A61K,A61P,C07K

Abstract:
An isolated and purified substance which inhibits neoplastic cell growth denominated Dolastatin 16 and having the following characteristics:Physical Data for Dolastatin 16IR (cm.sup.-1), KBr: 3300, 1600 and 1540;UV (nm), MeOH: 250, and 240-210;MS, HRFAB: 871.525713 [M+H].sup.+ ; andNMR, 500 MHZ, CLCl.sub.3 ;The .sup.1 H and .sup.13 C- MNR Spectral Data Assignments of Dolastatin 16 (in CDCl.sub.3) .sup.13 C .sup.1 H J HMBC No. ppm ppm (Hz) (.sup.1 H to .sup.13 C) Pro.sup.1 CO 172.24 s .alpha. 61.28 d 4.62 dd (7.2, 2.0) CO, .beta., .gamma., .delta. .beta. 30.70 t 2.18 m 2.26 m CO, .alpha., .gamma., .gamma. 24.78 t 1.99 m 2.08 m .beta. .delta. 47.55 t 3.45 m .gamma. 3.91 m .alpha., .beta., .gamma. Dpv.sup.2 CO 171.31 s .alpha. 50.59 d 4.95 d (7.2) Pro.sup.1 CO, CO, .beta., .gamma., .gamma.' .beta. 40.90 d 1.75 m .gamma. .gamma. 40.95 t 2.39 m .alpha., .beta., .gamma., 1, 2/6 2.52 d (7.6) .alpha., .beta., .gamma., 1, 2/6 .gamma.' 15.13 q 0.80 d (5.2) .alpha., .beta., .gamma. 1 140.60 s 2/6 129.66 d 7.35 d (6.0) .gamma., 4 3/4 128.33 d 7.27 d (6.0) 1 5 126.15 d 7.17 d (6.0, 6.0) 2/6 NH 6.73 d (7.2) Pro.sup.1 CO, CO Pro.sup.3 CO 171.01 s .alpha. 58.84 d 4.55 d (6.0) CO, .beta., .gamma., .delta. .beta. 25.49 t 1.51 m CO .gamma. 25.01 t 1.73 m .alpha. 1.84 m .delta. 45.89 t 2.52 m .beta. 2.83 m .gamma. Dml.sup.4 CO 174.64 s .alpha. 38.67 d 2.85 m CO, .beta.' .beta. 56.35 d 3.66 m Pro.sup.3, CO, CO, .alpha., .gamma. .beta.' 14.89 q 1.01 d (5.6) CO, .alpha., .beta. .gamma. 32.31 d 1.53 m .delta. 19.73 q 0.87 d (5.6) .beta., .gamma., .delta.' .delta.' 20.29 q 0.88 d (5.6) .beta., .gamma., .delta. NH 7.68 d (8.0) Pro.sup.3 CO Lac.sup.5 CO 169.02 s .alpha. 66.64 d 5.18 q (7.0) Dml.sup.4 CO, CO, .beta. .beta. 17.02 q 1.44 d (7.0) CO, .alpha. Pro.sup.6 CO 171.01 s .alpha. 57.82 d 4.45 d (6.4) CO, .beta., .gamma., .delta. .beta. 30.82 t 2.20 m CO 2.30 m CO, .delta. .gamma. 21.77 t 1.95 m 2.07 m .beta. .delta. 46.43 t 3.42 m .gamma. 3.67 m Hiv.sup.7 CO 169.57 s .alpha. 76.37 d 5.42 d (2.8) Pro.sup.6 CO, CO, .beta., .gamma., .gamma.' .beta. 28.29 d 2.18 m .gamma., .gamma.' .gamma. 16.08 q 1.04 d (7.0) .alpha., .beta., .gamma.' .gamma.' 19.73 q 1.06 d (7.2) .alpha., .beta., .gamma. MeVal.sup.8 CO 169.30 s .alpha. 59.46 d 5.16 (8.8) CO, .beta., .gamma., .gamma.', CH.sub.3 N .beta. 25.63 d 2.36 m .alpha., .gamma., .gamma.' .gamma. 19.73 q 0.91 d (5.6) .alpha., .beta., .gamma.' .gamma.' 17.75 q 0.83 d (5.2) .alpha., .beta., .gamma. CH.sub.3 N 29.26 q 3.09 s Hiv.sup.7 CO, CO